[{"volume":12,"file_date_updated":"2023-09-15T06:59:10Z","date_created":"2023-09-10T22:01:11Z","date_updated":"2023-09-15T07:07:10Z","abstract":[{"text":"During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transient proteolysis of four peripheral Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective, and we identified in an unbiased manner several classes of cytoplasmic, plasma membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic reticulum stress. Our results suggest that caspases can reversibly modulate nuclear transport activity, which allows them to function as agents of cell differentiation and adaptation at sublethal levels.","lang":"eng"}],"type":"journal_article","month":"09","oa_version":"Published Version","_id":"14315","acknowledgement":"We thank the members of the Hetzer laboratory, Tony Hunter (Salk), Lorenzo Puri (Sanford Burnham Prebys), and Jongmin Kim (Massachusetts General Hospital) for the critical reading of the manuscript; Kenneth Diffenderfer and Aimee Pankonin (Stem Cell Core at the Salk Institute) for help with neurogenesis; Carol Marchetto and Fred Gage (Salk) for providing H9 embryonic stem cells; Lorenzo Puri, Alexandra Sacco, and Luca Caputo (Sanford Burnham Prebys) for helpful discussions and sharing mouse primary myoblasts. This work was supported by a Glenn Foundation for Medical Research Postdoctoral Fellowship in Aging Research (UHC), the NOMIS foundation (MWH), and the National Institutes of Health (R01 NS096786 to MWH and K01 AR080828 to UHC). This work was also supported by the Mass Spectrometry Core of the Salk Institute with funding from NIH-NCI CCSG: P30 014195 and the Helmsley Center for Genomic Medicine. We thank Jolene Diedrich and Antonio Pinto for technical support.","year":"2023","date_published":"2023-09-04T00:00:00Z","ddc":["570"],"oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":"        12","citation":{"short":"U.H. Cho, M. Hetzer, ELife 12 (2023).","ieee":"U. H. Cho and M. Hetzer, “Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2023.","chicago":"Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>. eLife Sciences Publications, 2023. <a href=\"https://doi.org/10.7554/eLife.89066\">https://doi.org/10.7554/eLife.89066</a>.","ista":"Cho UH, Hetzer M. 2023. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. eLife. 12, RP89066.","mla":"Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>, vol. 12, RP89066, eLife Sciences Publications, 2023, doi:<a href=\"https://doi.org/10.7554/eLife.89066\">10.7554/eLife.89066</a>.","apa":"Cho, U. H., &#38; Hetzer, M. (2023). Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.89066\">https://doi.org/10.7554/eLife.89066</a>","ama":"Cho UH, Hetzer M. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. <i>eLife</i>. 2023;12. doi:<a href=\"https://doi.org/10.7554/eLife.89066\">10.7554/eLife.89066</a>"},"status":"public","external_id":{"pmid":["37665327"]},"title":"Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress","article_number":"RP89066","author":[{"first_name":"Ukrae H.","last_name":"Cho","full_name":"Cho, Ukrae H."},{"last_name":"Hetzer","first_name":"Martin W","full_name":"Hetzer, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X"}],"file":[{"file_id":"14336","date_updated":"2023-09-15T06:59:10Z","checksum":"db24bf3d595507387b48d3799c33e289","date_created":"2023-09-15T06:59:10Z","access_level":"open_access","file_name":"2023_eLife_Cho.pdf","success":1,"file_size":3703097,"content_type":"application/pdf","relation":"main_file","creator":"dernst"}],"day":"04","publication":"eLife","scopus_import":"1","article_processing_charge":"Yes","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","publisher":"eLife Sciences Publications","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"department":[{"_id":"MaHe"}],"doi":"10.7554/eLife.89066","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"language":[{"iso":"eng"}]},{"status":"public","external_id":{"isi":["001035372800001"],"pmid":["37477116"]},"intvolume":"        12","citation":{"ieee":"J. Y. Toshima <i>et al.</i>, “The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2023.","chicago":"Toshima, Junko Y., Ayana Tsukahara, Makoto Nagano, Takuro Tojima, Daria E Siekhaus, Akihiko Nakano, and Jiro Toshima. “The Yeast Endocytic Early/Sorting Compartment Exists as an Independent Sub-Compartment within the Trans-Golgi Network.” <i>ELife</i>. eLife Sciences Publications, 2023. <a href=\"https://doi.org/10.7554/eLife.84850\">https://doi.org/10.7554/eLife.84850</a>.","short":"J.Y. Toshima, A. Tsukahara, M. Nagano, T. Tojima, D.E. Siekhaus, A. Nakano, J. Toshima, ELife 12 (2023).","ama":"Toshima JY, Tsukahara A, Nagano M, et al. The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network. <i>eLife</i>. 2023;12. doi:<a href=\"https://doi.org/10.7554/eLife.84850\">10.7554/eLife.84850</a>","ista":"Toshima JY, Tsukahara A, Nagano M, Tojima T, Siekhaus DE, Nakano A, Toshima J. 2023. The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network. eLife. 12, e84850.","mla":"Toshima, Junko Y., et al. “The Yeast Endocytic Early/Sorting Compartment Exists as an Independent Sub-Compartment within the Trans-Golgi Network.” <i>ELife</i>, vol. 12, e84850, eLife Sciences Publications, 2023, doi:<a href=\"https://doi.org/10.7554/eLife.84850\">10.7554/eLife.84850</a>.","apa":"Toshima, J. Y., Tsukahara, A., Nagano, M., Tojima, T., Siekhaus, D. E., Nakano, A., &#38; Toshima, J. (2023). The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.84850\">https://doi.org/10.7554/eLife.84850</a>"},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2023-07-21T00:00:00Z","acknowledgement":"This work was supported by JSPS KAKENHI grant #18K062291, and the Takeda Science Foundation to JYT., as well as JSPS KAKENHI grant #19K065710, the Takeda Science Foundation, and Life Science Foundation of Japan to JT.","year":"2023","_id":"13316","date_updated":"2023-12-13T11:37:36Z","abstract":[{"lang":"eng","text":"Although budding yeast has been extensively used as a model organism for studying organelle functions and intracellular vesicle trafficking, whether it possesses an independent endocytic early/sorting compartment that sorts endocytic cargos to the endo-lysosomal pathway or the recycling pathway has long been unclear. The structure and properties of the endocytic early/sorting compartment differ significantly between organisms; in plant cells, the trans-Golgi network (TGN) serves this role, whereas in mammalian cells a separate intracellular structure performs this function. The yeast syntaxin homolog Tlg2p, widely localizing to the TGN and endosomal compartments, is presumed to act as a Q-SNARE for endocytic vesicles, but which compartment is the direct target for endocytic vesicles remained unanswered. Here we demonstrate by high-speed and high-resolution 4D imaging of fluorescently labeled endocytic cargos that the Tlg2p-residing compartment within the TGN functions as the early/sorting compartment. After arriving here, endocytic cargos are recycled to the plasma membrane or transported to the yeast Rab5-residing endosomal compartment through the pathway requiring the clathrin adaptors GGAs. Interestingly, Gga2p predominantly localizes at the Tlg2p-residing compartment, and the deletion of GGAs has little effect on another TGN region where Sec7p is present but suppresses dynamics of the Tlg2-residing early/sorting compartment, indicating that the Tlg2p- and Sec7p-residing regions are discrete entities in the mutant. Thus, the Tlg2p-residing region seems to serve as an early/sorting compartment and function independently of the Sec7p-residing region within the TGN."}],"type":"journal_article","month":"07","oa_version":"Published Version","volume":12,"file_date_updated":"2023-07-31T07:43:00Z","date_created":"2023-07-30T22:01:02Z","isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.84850","quality_controlled":"1","publisher":"eLife Sciences Publications","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"department":[{"_id":"DaSi"}],"publication":"eLife","article_processing_charge":"Yes","scopus_import":"1","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","author":[{"full_name":"Toshima, Junko Y.","last_name":"Toshima","first_name":"Junko Y."},{"last_name":"Tsukahara","first_name":"Ayana","full_name":"Tsukahara, Ayana"},{"first_name":"Makoto","last_name":"Nagano","full_name":"Nagano, Makoto"},{"full_name":"Tojima, Takuro","last_name":"Tojima","first_name":"Takuro"},{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","last_name":"Siekhaus","first_name":"Daria E"},{"full_name":"Nakano, Akihiko","last_name":"Nakano","first_name":"Akihiko"},{"last_name":"Toshima","first_name":"Jiro","full_name":"Toshima, Jiro"}],"file":[{"file_name":"2023_eLife_Toshima.pdf","success":1,"creator":"dernst","file_size":11980913,"content_type":"application/pdf","relation":"main_file","checksum":"2af111a00cf5e3a956f7f0fd13199b15","file_id":"13324","date_updated":"2023-07-31T07:43:00Z","access_level":"open_access","date_created":"2023-07-31T07:43:00Z"}],"day":"21","title":"The yeast endocytic early/sorting compartment exists as an independent sub-compartment within the trans-Golgi network","article_number":"e84850"},{"volume":11,"date_created":"2022-02-06T23:01:32Z","file_date_updated":"2022-02-07T07:14:09Z","month":"01","type":"journal_article","oa_version":"Published Version","date_updated":"2023-08-02T14:09:02Z","abstract":[{"text":"Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought.","lang":"eng"}],"_id":"10736","acknowledgement":"We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao, Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML; IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme 7 (2007–2013, grant agreement number 648440) to JPB.","year":"2022","date_published":"2022-01-26T00:00:00Z","ddc":["576"],"publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"        11","citation":{"chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>.","ieee":"M. Lagator <i>et al.</i>, “Predicting bacterial promoter function and evolution from random sequences,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","ama":"Lagator M, Sarikas S, Steinrueck M, et al. Predicting bacterial promoter function and evolution from random sequences. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>","apa":"Lagator, M., Sarikas, S., Steinrueck, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., &#38; Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>","mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>, vol. 11, e64543, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>.","ista":"Lagator M, Sarikas S, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543."},"external_id":{"pmid":["35080492"],"isi":["000751104400001"]},"status":"public","article_number":"e64543","title":"Predicting bacterial promoter function and evolution from random sequences","author":[{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"full_name":"Sarikas, Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan","last_name":"Sarikas"},{"first_name":"Magdalena","last_name":"Steinrueck","full_name":"Steinrueck, Magdalena"},{"last_name":"Toledo-Aparicio","first_name":"David","full_name":"Toledo-Aparicio, David"},{"first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"file":[{"access_level":"open_access","date_created":"2022-02-07T07:14:09Z","checksum":"decdcdf600ff51e9a9703b49ca114170","file_id":"10739","date_updated":"2022-02-07T07:14:09Z","creator":"cchlebak","file_size":5604343,"content_type":"application/pdf","relation":"main_file","file_name":"2022_ELife_Lagator.pdf","success":1}],"day":"26","publication":"eLife","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","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"pmid":1,"doi":"10.7554/eLife.64543","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"isi":1,"language":[{"iso":"eng"}],"project":[{"grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}]},{"publication_identifier":{"eissn":["2050-084X"]},"quality_controlled":"1","doi":"10.7554/eLife.73542","language":[{"iso":"eng"}],"isi":1,"day":"05","file":[{"date_updated":"2022-05-30T08:09:16Z","file_id":"11421","checksum":"ccddbd167e00ff8375f12998af497152","date_created":"2022-05-30T08:09:16Z","access_level":"open_access","success":1,"file_name":"elife-73542-v2.pdf","relation":"main_file","content_type":"application/pdf","file_size":2466296,"creator":"cchlebak"}],"author":[{"full_name":"Hori, Tetsuya","first_name":"Tetsuya","last_name":"Hori"},{"first_name":"Kohgaku","last_name":"Eguchi","full_name":"Eguchi, Kohgaku","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6170-2546"},{"last_name":"Wang","first_name":"Han Ying","full_name":"Wang, Han Ying"},{"full_name":"Miyasaka, Tomohiro","first_name":"Tomohiro","last_name":"Miyasaka"},{"full_name":"Guillaud, Laurent","last_name":"Guillaud","first_name":"Laurent"},{"full_name":"Taoufiq, Zacharie","first_name":"Zacharie","last_name":"Taoufiq"},{"full_name":"Mahapatra, Satyajit","first_name":"Satyajit","last_name":"Mahapatra"},{"last_name":"Yamada","first_name":"Hiroshi","full_name":"Yamada, Hiroshi"},{"first_name":"Kohji","last_name":"Takei","full_name":"Takei, Kohji"},{"last_name":"Takahashi","first_name":"Tomoyuki","full_name":"Takahashi, Tomoyuki"}],"title":"Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer's disease synapse model","article_number":"e73542","pmid":1,"department":[{"_id":"RySh"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","scopus_import":"1","article_processing_charge":"No","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)"},"publication":"eLife","has_accepted_license":"1","publication_status":"published","oa":1,"date_published":"2022-05-05T00:00:00Z","ddc":["616"],"external_id":{"isi":["000876231600001"],"pmid":["35471147 "]},"status":"public","citation":{"short":"T. Hori, K. Eguchi, H.Y. Wang, T. Miyasaka, L. Guillaud, Z. Taoufiq, S. Mahapatra, H. Yamada, K. Takei, T. Takahashi, ELife 11 (2022).","chicago":"Hori, Tetsuya, Kohgaku Eguchi, Han Ying Wang, Tomohiro Miyasaka, Laurent Guillaud, Zacharie Taoufiq, Satyajit Mahapatra, Hiroshi Yamada, Kohji Takei, and Tomoyuki Takahashi. “Microtubule Assembly by Tau Impairs Endocytosis and Neurotransmission via Dynamin Sequestration in Alzheimer’s Disease Synapse Model.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.73542\">https://doi.org/10.7554/eLife.73542</a>.","ieee":"T. Hori <i>et al.</i>, “Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Hori, T., Eguchi, K., Wang, H. Y., Miyasaka, T., Guillaud, L., Taoufiq, Z., … Takahashi, T. (2022). Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.73542\">https://doi.org/10.7554/eLife.73542</a>","ista":"Hori T, Eguchi K, Wang HY, Miyasaka T, Guillaud L, Taoufiq Z, Mahapatra S, Yamada H, Takei K, Takahashi T. 2022. Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model. eLife. 11, e73542.","mla":"Hori, Tetsuya, et al. “Microtubule Assembly by Tau Impairs Endocytosis and Neurotransmission via Dynamin Sequestration in Alzheimer’s Disease Synapse Model.” <i>ELife</i>, vol. 11, e73542, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.73542\">10.7554/eLife.73542</a>.","ama":"Hori T, Eguchi K, Wang HY, et al. Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.73542\">10.7554/eLife.73542</a>"},"intvolume":"        11","abstract":[{"text":"Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimer’s disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in slices from mice brainstem. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10–20 µM caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased MT-bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin 1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission.","lang":"eng"}],"date_updated":"2023-08-03T07:15:49Z","oa_version":"Published Version","type":"journal_article","month":"05","date_created":"2022-05-29T22:01:54Z","file_date_updated":"2022-05-30T08:09:16Z","volume":11,"year":"2022","acknowledgement":"We thank Yasuo Ihara, Nobuyuki Nukina, and Takeshi Sakaba for comments and Patrick Stoney for editing this paper. We also thank Shota Okuda and Mikako Matsubara for their contributions in the early stage of this study, and Satoko Wada-Kakuda for technical assistant with in vitro analysis of tau. This research was supported by funding from Okinawa Institute of Science and Technology and from Technology (OIST) and Core Research for the Evolutional Science and Technology of Japan Science and Technology Agency (CREST) to TT, and by Scientific Research on Innovative Areas to TM (Brain Protein Aging and Dementia Control 26117004).","_id":"11419"},{"volume":11,"file_date_updated":"2022-08-16T08:57:37Z","date_created":"2022-08-14T22:01:46Z","date_updated":"2023-08-03T12:54:21Z","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"oa_version":"Published Version","type":"journal_article","month":"07","_id":"11843","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","year":"2022","ddc":["570"],"date_published":"2022-07-26T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"publication_status":"published","oa":1,"has_accepted_license":"1","related_material":{"record":[{"status":"public","id":"10316","relation":"earlier_version"}]},"intvolume":"        11","citation":{"apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022."},"external_id":{"isi":["000838410200001"]},"status":"public","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","article_number":"e78995","author":[{"first_name":"Kathrin","last_name":"Tomasek","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexander F","last_name":"Leithner","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"first_name":"Ivana","last_name":"Glatzová","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","full_name":"Glatzová, Ivana"},{"last_name":"Lukesch","first_name":"Michael S.","full_name":"Lukesch, Michael S."},{"first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K"}],"day":"26","file":[{"file_size":2057577,"content_type":"application/pdf","relation":"main_file","creator":"cchlebak","file_name":"2022_eLife_Tomasek.pdf","success":1,"date_created":"2022-08-16T08:57:37Z","access_level":"open_access","file_id":"11861","date_updated":"2022-08-16T08:57:37Z","checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4"}],"publication":"eLife","article_processing_charge":"Yes","scopus_import":"1","ec_funded":1,"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","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"doi":"10.7554/eLife.78995","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"isi":1,"language":[{"iso":"eng"}],"project":[{"grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients"},{"name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29911"}]},{"ddc":["570"],"date_published":"2022-09-26T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"ieee":"L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","chicago":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>.","short":"L. Hayward, G. Sella, ELife 11 (2022).","ama":"Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>","ista":"Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697.","mla":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>, vol. 11, 66697, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>.","apa":"Hayward, L., &#38; Sella, G. (2022). Polygenic adaptation after a sudden change in environment. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>"},"intvolume":"        11","external_id":{"isi":["000890735600001"]},"status":"public","date_created":"2023-01-12T12:09:00Z","file_date_updated":"2023-01-24T12:21:32Z","volume":11,"date_updated":"2023-08-04T09:04:58Z","abstract":[{"text":"Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.","lang":"eng"}],"oa_version":"Published Version","month":"09","type":"journal_article","_id":"12157","year":"2022","acknowledgement":"We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372 Laura Katharine Hayward","quality_controlled":"1","doi":"10.7554/elife.66697","publication_identifier":{"eissn":["2050-084X"]},"language":[{"iso":"eng"}],"isi":1,"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"title":"Polygenic adaptation after a sudden change in environment","article_number":"66697","day":"26","file":[{"file_id":"12363","date_updated":"2023-01-24T12:21:32Z","checksum":"28de155b231ac1c8d4501c98b2fb359a","date_created":"2023-01-24T12:21:32Z","access_level":"open_access","file_name":"2022_eLife_Hayward.pdf","success":1,"file_size":18935612,"content_type":"application/pdf","relation":"main_file","creator":"dernst"}],"author":[{"id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","full_name":"Hayward, Laura","first_name":"Laura","last_name":"Hayward"},{"full_name":"Sella, Guy","last_name":"Sella","first_name":"Guy"}],"scopus_import":"1","article_processing_charge":"No","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)"},"publication":"eLife","department":[{"_id":"NiBa"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications"},{"year":"2022","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","_id":"12288","oa_version":"Published Version","month":"09","type":"journal_article","abstract":[{"lang":"eng","text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo."}],"date_updated":"2023-08-04T10:29:48Z","date_created":"2023-01-16T10:04:15Z","file_date_updated":"2023-01-30T11:50:53Z","volume":11,"external_id":{"pmid":["36040301"],"isi":["000892204300001"]},"status":"public","citation":{"ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>"},"intvolume":"        11","has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"ddc":["570"],"date_published":"2022-09-15T00:00:00Z","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","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)"},"article_processing_charge":"No","scopus_import":"1","ec_funded":1,"publication":"eLife","file":[{"file_size":8506811,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_name":"2022_eLife_Sumser.pdf","success":1,"date_created":"2023-01-30T11:50:53Z","access_level":"open_access","file_id":"12463","date_updated":"2023-01-30T11:50:53Z","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b"}],"day":"15","author":[{"last_name":"Sumser","first_name":"Anton L","orcid":"0000-0002-4792-1881","id":"3320A096-F248-11E8-B48F-1D18A9856A87","full_name":"Sumser, Anton L"},{"orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A","last_name":"Jösch","first_name":"Maximilian A"},{"first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav"}],"article_number":"79848","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention","grant_number":"756502"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 1098-2017","name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"isi":1,"publication_identifier":{"eissn":["2050-084X"]},"quality_controlled":"1","doi":"10.7554/elife.79848"},{"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"}],"publication":"eLife","scopus_import":"1","article_processing_charge":"No","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)"},"author":[{"full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","id":"3981F020-F248-11E8-B48F-1D18A9856A87","last_name":"Tomanek","first_name":"Isabella"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet"}],"day":"22","file":[{"file_size":8835954,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_name":"2022_eLife_Tomanek.pdf","success":1,"date_created":"2023-01-23T08:56:21Z","access_level":"open_access","file_id":"12338","date_updated":"2023-01-23T08:56:21Z","checksum":"9321fd5f06ff59d5e2d33daee84b3da1"}],"title":"Adaptation dynamics between copynumber and point mutations","article_number":"e82240","isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/ELIFE.82240","quality_controlled":"1","acknowledgement":"We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska, R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek for help with flow cytometry.","year":"2022","_id":"12333","abstract":[{"text":"Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term amplification hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales.","lang":"eng"}],"date_updated":"2023-08-03T14:23:07Z","oa_version":"Published Version","type":"journal_article","month":"12","volume":11,"file_date_updated":"2023-01-23T08:56:21Z","date_created":"2023-01-22T23:00:55Z","status":"public","external_id":{"isi":["000912674700001"]},"related_material":{"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.6974122"}],"record":[{"id":"12339","status":"public","relation":"research_data"}]},"intvolume":"        11","citation":{"ama":"Tomanek I, Guet CC. Adaptation dynamics between copynumber and point mutations. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/ELIFE.82240\">10.7554/ELIFE.82240</a>","apa":"Tomanek, I., &#38; Guet, C. C. (2022). Adaptation dynamics between copynumber and point mutations. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>","mla":"Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>, vol. 11, e82240, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/ELIFE.82240\">10.7554/ELIFE.82240</a>.","ista":"Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point mutations. eLife. 11, e82240.","chicago":"Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>.","ieee":"I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point mutations,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"I. Tomanek, C.C. Guet, ELife 11 (2022)."},"oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2022-12-22T00:00:00Z","ddc":["570"]},{"file":[{"checksum":"79897a09bfecd9914d39c4aea2841855","file_id":"9268","date_updated":"2021-03-22T07:36:08Z","access_level":"open_access","date_created":"2021-03-22T07:36:08Z","file_name":"2021_eLife_HernandezRocamora.pdf","success":1,"creator":"dernst","file_size":2314698,"content_type":"application/pdf","relation":"main_file"}],"day":"24","author":[{"last_name":"Hernández-Rocamora","first_name":"Víctor M.","full_name":"Hernández-Rocamora, Víctor M."},{"orcid":"0000-0002-3086-9124","id":"38661662-F248-11E8-B48F-1D18A9856A87","full_name":"Baranova, Natalia S.","last_name":"Baranova","first_name":"Natalia S."},{"full_name":"Peters, Katharina","first_name":"Katharina","last_name":"Peters"},{"last_name":"Breukink","first_name":"Eefjan","full_name":"Breukink, Eefjan"},{"last_name":"Loose","first_name":"Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin"},{"full_name":"Vollmer, Waldemar","last_name":"Vollmer","first_name":"Waldemar"}],"article_number":"1-32","title":"Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins","department":[{"_id":"MaLo"}],"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","publication":"eLife","publication_identifier":{"eissn":["2050-084X"]},"quality_controlled":"1","doi":"10.7554/eLife.61525","project":[{"grant_number":"679239","call_identifier":"H2020","_id":"2595697A-B435-11E9-9278-68D0E5697425","name":"Self-Organization of the Bacterial Cell"},{"_id":"2596EAB6-B435-11E9-9278-68D0E5697425","name":"Synthesis of bacterial cell wall","grant_number":"ALTF 2015-1163"},{"_id":"259B655A-B435-11E9-9278-68D0E5697425","name":"Reconstitution of bacterial cell wall sythesis","grant_number":"LT000824/2016"}],"language":[{"iso":"eng"}],"isi":1,"type":"journal_article","month":"02","oa_version":"Published Version","date_updated":"2023-08-07T14:10:50Z","abstract":[{"lang":"eng","text":"Peptidoglycan is an essential component of the bacterial cell envelope that surrounds the cytoplasmic membrane to protect the cell from osmotic lysis. Important antibiotics such as β-lactams and glycopeptides target peptidoglycan biosynthesis. Class A penicillin-binding proteins (PBPs) are bifunctional membrane-bound peptidoglycan synthases that polymerize glycan chains and connect adjacent stem peptides by transpeptidation. How these enzymes work in their physiological membrane environment is poorly understood. Here, we developed a novel Förster resonance energy transfer-based assay to follow in real time both reactions of class A PBPs reconstituted in liposomes or supported lipid bilayers and applied this assay with PBP1B homologues from Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii in the presence or absence of their cognate lipoprotein activator. Our assay will allow unravelling the mechanisms of peptidoglycan synthesis in a lipid-bilayer environment and can be further developed to be used for high-throughput screening for new antimicrobials."}],"file_date_updated":"2021-03-22T07:36:08Z","date_created":"2021-03-14T23:01:33Z","volume":10,"year":"2021","acknowledgement":"We thank Alexander Egan (Newcastle University) for purified proteins LpoB(sol) and LpoPPa(sol), Federico Corona (Newcastle University) for purified MepM, and Oliver Birkholz and Jacob Piehler (Department of Biology and Center of Cellular Nanoanalytics, University of Osnabru¨ ck) for their help with PBP1B reconstitution into polymer-SLBs and initial guidance on single particle tracking. We also acknowledge Christian P Richter and Changjiang You (Department of Biology and Center of Cellular Nanoanalytics, University of Osnabru¨ ck) for providing SLIMfast software and tris-DODA-NTA reagent, respectively. This work was funded by the BBSRC grant BB/R017409/1 (to WV), the European Research Council through grant ERC-2015-StG-679239 (to ML), and long-term fellowships HFSP LT 000824/2016-L4 and EMBO ALTF 1163–2015 (to NB). ","_id":"9243","has_accepted_license":"1","publication_status":"published","oa":1,"ddc":["570"],"date_published":"2021-02-24T00:00:00Z","status":"public","external_id":{"isi":["000627596400001"]},"citation":{"ama":"Hernández-Rocamora VM, Baranova NS, Peters K, Breukink E, Loose M, Vollmer W. Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.61525\">10.7554/eLife.61525</a>","apa":"Hernández-Rocamora, V. M., Baranova, N. S., Peters, K., Breukink, E., Loose, M., &#38; Vollmer, W. (2021). Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.61525\">https://doi.org/10.7554/eLife.61525</a>","mla":"Hernández-Rocamora, Víctor M., et al. “Real Time Monitoring of Peptidoglycan Synthesis by Membrane-Reconstituted Penicillin Binding Proteins.” <i>ELife</i>, vol. 10, 1–32, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.61525\">10.7554/eLife.61525</a>.","ista":"Hernández-Rocamora VM, Baranova NS, Peters K, Breukink E, Loose M, Vollmer W. 2021. Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins. eLife. 10, 1–32.","chicago":"Hernández-Rocamora, Víctor M., Natalia S. Baranova, Katharina Peters, Eefjan Breukink, Martin Loose, and Waldemar Vollmer. “Real Time Monitoring of Peptidoglycan Synthesis by Membrane-Reconstituted Penicillin Binding Proteins.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.61525\">https://doi.org/10.7554/eLife.61525</a>.","ieee":"V. M. Hernández-Rocamora, N. S. Baranova, K. Peters, E. Breukink, M. Loose, and W. Vollmer, “Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","short":"V.M. Hernández-Rocamora, N.S. Baranova, K. Peters, E. Breukink, M. Loose, W. Vollmer, ELife 10 (2021)."},"intvolume":"        10"},{"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/ELIFE.68274","quality_controlled":"1","project":[{"call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385"}],"isi":1,"language":[{"iso":"eng"}],"author":[{"full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep","last_name":"Bhandari"},{"full_name":"Vandael, David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","last_name":"Vandael","first_name":"David H"},{"last_name":"Fernández-Fernández","first_name":"Diego","full_name":"Fernández-Fernández, Diego"},{"full_name":"Fritzius, Thorsten","last_name":"Fritzius","first_name":"Thorsten"},{"id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David","first_name":"David","last_name":"Kleindienst"},{"full_name":"Önal, Hüseyin C","orcid":"0000-0002-2771-2011","id":"4659D740-F248-11E8-B48F-1D18A9856A87","first_name":"Hüseyin C","last_name":"Önal"},{"first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gassmann, Martin","last_name":"Gassmann","first_name":"Martin"},{"first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"},{"first_name":"Akos","last_name":"Kulik","full_name":"Kulik, Akos"},{"full_name":"Bettler, Bernhard","last_name":"Bettler","first_name":"Bernhard"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner"}],"file":[{"file_name":"2021_eLife_Bhandari.pdf","success":1,"creator":"cziletti","file_size":8174719,"relation":"main_file","content_type":"application/pdf","checksum":"6ebcb79999f889766f7cd79ee134ad28","file_id":"9440","date_updated":"2021-05-31T09:43:09Z","access_level":"open_access","date_created":"2021-05-31T09:43:09Z"}],"day":"29","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","article_number":"e68274","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"RySh"},{"_id":"PeJo"}],"publication":"eLife","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","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)"},"publication_status":"published","oa":1,"has_accepted_license":"1","ddc":["570"],"date_published":"2021-04-29T00:00:00Z","status":"public","external_id":{"isi":["000651761700001"]},"intvolume":"        10","related_material":{"record":[{"relation":"dissertation_contains","id":"9562","status":"public"}],"link":[{"url":"https://doi.org/10.1101/2020.04.16.045112","relation":"earlier_version"}]},"citation":{"ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>"},"date_updated":"2024-03-25T23:30:16Z","abstract":[{"lang":"eng","text":"The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation."}],"oa_version":"Published Version","month":"04","type":"journal_article","volume":10,"file_date_updated":"2021-05-31T09:43:09Z","date_created":"2021-05-30T22:01:23Z","acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","year":"2021","_id":"9437"},{"abstract":[{"text":"The ubiquitous Ca2+ sensor calmodulin (CaM) binds and regulates many proteins, including ion channels, CaM kinases, and calcineurin, according to Ca2+-CaM levels. What regulates neuronal CaM levels, is, however, unclear. CaM-binding transcription activators (CAMTAs) are ancient proteins expressed broadly in nervous systems and whose loss confers pleiotropic behavioral defects in flies, mice, and humans. Using Caenorhabditis elegans and Drosophila, we show that CAMTAs control neuronal CaM levels. The behavioral and neuronal Ca2+ signaling defects in mutants lacking camt-1, the sole C. elegans CAMTA, can be rescued by supplementing neuronal CaM. CAMT-1 binds multiple sites in the CaM promoter and deleting these sites phenocopies camt-1. Our data suggest CAMTAs mediate a conserved and general mechanism that controls neuronal CaM levels, thereby regulating Ca2+ signaling, physiology, and behavior.","lang":"eng"}],"date_updated":"2023-08-14T07:23:39Z","type":"journal_article","oa_version":"Published Version","month":"09","volume":10,"date_created":"2021-10-10T22:01:22Z","file_date_updated":"2021-10-11T14:15:07Z","acknowledgement":"The authors thank the MRC-LMB Flow Cytometry facility and Imaging Service for support, the Cancer Research UK Cambridge Institute Genomics Core for Next Generation Sequencing, Julie Ahringer and Alex Appert for advice and technical help for ChIP-seq experiments, Paula Freire-Pritchett, Tim Stevens, and Gurpreet Ghattaoraya for RNA-seq and ChIP-seq analyses, Nikos Chronis for the TN-XL plasmid, Hong-Sheng Li and Daisuke Yamamoto for generously sending the tes2 and cro mutants, Daria Siekhaus for hosting the fly work, Michaela Misova for technical assistance. The authors are very grateful to Salihah Ece Sönmez for teaching us how to dissect, mount and stain Drosophila retinae. This work was supported by an Advanced ERC grant (269058 ACMO) and a Wellcome Investigator Award (209504/Z/17/Z) to MdB, and an IST Plus Fellowship to TV-B (Marie Sklodowska-Curie Agreement no 754411).","year":"2021","_id":"10116","publication_status":"published","oa":1,"has_accepted_license":"1","date_published":"2021-09-17T00:00:00Z","ddc":["610"],"status":"public","external_id":{"isi":["000695716100001"],"pmid":["34499028"]},"intvolume":"        10","citation":{"ama":"Vuong-Brender T, Flynn S, Vallis Y, de Bono M. Neuronal calmodulin levels are controlled by CAMTA transcription factors. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.68238\">10.7554/eLife.68238</a>","apa":"Vuong-Brender, T., Flynn, S., Vallis, Y., &#38; de Bono, M. (2021). Neuronal calmodulin levels are controlled by CAMTA transcription factors. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.68238\">https://doi.org/10.7554/eLife.68238</a>","mla":"Vuong-Brender, Thanh, et al. “Neuronal Calmodulin Levels Are Controlled by CAMTA Transcription Factors.” <i>ELife</i>, vol. 10, e68238, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.68238\">10.7554/eLife.68238</a>.","ista":"Vuong-Brender T, Flynn S, Vallis Y, de Bono M. 2021. Neuronal calmodulin levels are controlled by CAMTA transcription factors. eLife. 10, e68238.","chicago":"Vuong-Brender, Thanh, Sean Flynn, Yvonne Vallis, and Mario de Bono. “Neuronal Calmodulin Levels Are Controlled by CAMTA Transcription Factors.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.68238\">https://doi.org/10.7554/eLife.68238</a>.","ieee":"T. Vuong-Brender, S. Flynn, Y. Vallis, and M. de Bono, “Neuronal calmodulin levels are controlled by CAMTA transcription factors,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","short":"T. Vuong-Brender, S. Flynn, Y. Vallis, M. de Bono, ELife 10 (2021)."},"author":[{"first_name":"Thanh","last_name":"Vuong-Brender","id":"D389312E-10C4-11EA-ABF4-A4B43DDC885E","full_name":"Vuong-Brender, Thanh"},{"first_name":"Sean","last_name":"Flynn","full_name":"Flynn, Sean"},{"full_name":"Vallis, Yvonne","id":"05A2795C-31B5-11EA-83A7-7DA23DDC885E","last_name":"Vallis","first_name":"Yvonne"},{"full_name":"De Bono, Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443","last_name":"De Bono","first_name":"Mario"}],"day":"17","file":[{"content_type":"application/pdf","relation":"main_file","file_size":1774624,"creator":"cchlebak","success":1,"file_name":"2021_eLife_VuongBrender.pdf","date_created":"2021-10-11T14:15:07Z","access_level":"open_access","date_updated":"2021-10-11T14:15:07Z","file_id":"10122","checksum":"b465e172d2b1f57aa26a2571a085d052"}],"title":"Neuronal calmodulin levels are controlled by CAMTA transcription factors","article_number":"e68238","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"MaDe"}],"publication":"eLife","article_processing_charge":"No","ec_funded":1,"scopus_import":"1","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","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.68238","quality_controlled":"1","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"isi":1,"language":[{"iso":"eng"}]},{"doi":"10.7554/eLife.65954","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"isi":1,"language":[{"iso":"eng"}],"article_number":"e65954","title":"Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons","author":[{"full_name":"Biane, Celia","last_name":"Biane","first_name":"Celia"},{"full_name":"Rückerl, Florian","first_name":"Florian","last_name":"Rückerl"},{"last_name":"Abrahamsson","first_name":"Therese","full_name":"Abrahamsson, Therese"},{"first_name":"Cécile","last_name":"Saint-Cloment","full_name":"Saint-Cloment, Cécile"},{"last_name":"Mariani","first_name":"Jean","full_name":"Mariani, Jean"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"David A.","last_name":"Digregorio","full_name":"Digregorio, David A."},{"full_name":"Sherrard, Rachel M.","last_name":"Sherrard","first_name":"Rachel M."},{"last_name":"Cathala","first_name":"Laurence","full_name":"Cathala, Laurence"}],"day":"03","file":[{"date_created":"2021-12-10T08:31:41Z","access_level":"open_access","date_updated":"2021-12-10T08:31:41Z","file_id":"10528","checksum":"c7c33c3319428d56e332e22349c50ed3","content_type":"application/pdf","relation":"main_file","file_size":13131322,"creator":"cchlebak","success":1,"file_name":"2021_eLife_Biane.pdf"}],"publication":"eLife","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","article_processing_charge":"No","scopus_import":"1","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"RySh"}],"ddc":["570"],"date_published":"2021-11-03T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"        10","citation":{"short":"C. Biane, F. Rückerl, T. Abrahamsson, C. Saint-Cloment, J. Mariani, R. Shigemoto, D.A. Digregorio, R.M. Sherrard, L. Cathala, ELife 10 (2021).","ieee":"C. Biane <i>et al.</i>, “Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Biane, Celia, Florian Rückerl, Therese Abrahamsson, Cécile Saint-Cloment, Jean Mariani, Ryuichi Shigemoto, David A. Digregorio, Rachel M. Sherrard, and Laurence Cathala. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.65954\">https://doi.org/10.7554/eLife.65954</a>.","ista":"Biane C, Rückerl F, Abrahamsson T, Saint-Cloment C, Mariani J, Shigemoto R, Digregorio DA, Sherrard RM, Cathala L. 2021. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 10, e65954.","mla":"Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” <i>ELife</i>, vol. 10, e65954, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.65954\">10.7554/eLife.65954</a>.","apa":"Biane, C., Rückerl, F., Abrahamsson, T., Saint-Cloment, C., Mariani, J., Shigemoto, R., … Cathala, L. (2021). Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.65954\">https://doi.org/10.7554/eLife.65954</a>","ama":"Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.65954\">10.7554/eLife.65954</a>"},"status":"public","external_id":{"isi":["000715789500001"]},"volume":10,"date_created":"2021-12-05T23:01:40Z","file_date_updated":"2021-12-10T08:31:41Z","month":"11","type":"journal_article","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits."}],"date_updated":"2023-08-14T13:12:07Z","_id":"10403","acknowledgement":"This study was supported by the Centre National de la Recherche Scientifique and the Agence Nationale de la Recherche (ANR-13-BSV4-00166, to LC and DAD). TA was supported by fellowships from the Fondation pour la Recherche Medicale and the Swedish Research Council. We thank Dmitry Ershov from the Image Analysis Hub of the Institut Pasteur, Elodie Le Monnier, Elena Hollergschwandtner, Vanessa Zheden, and Corinne Nantet for technical support and Haining Zhong for providing the Venus-tagged PSD95 mouse line. We would like to thank Alberto Bacci, Ann Lohof, and Nelson Rebola for comments on the manuscript.","year":"2021"},{"acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"}],"ddc":["570"],"date_published":"2021-12-21T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"ieee":"B. G. Godard, R. Dumollard, C.-P. J. Heisenberg, and A. Mcdougall, “Combined effect of cell geometry and polarity domains determines the orientation of unequal division,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Godard, Benoit G, Remi Dumollard, Carl-Philipp J Heisenberg, and Alex Mcdougall. “Combined Effect of Cell Geometry and Polarity Domains Determines the Orientation of Unequal Division.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.75639\">https://doi.org/10.7554/eLife.75639</a>.","short":"B.G. Godard, R. Dumollard, C.-P.J. Heisenberg, A. Mcdougall, ELife 10 (2021).","ama":"Godard BG, Dumollard R, Heisenberg C-PJ, Mcdougall A. Combined effect of cell geometry and polarity domains determines the orientation of unequal division. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.75639\">10.7554/eLife.75639</a>","ista":"Godard BG, Dumollard R, Heisenberg C-PJ, Mcdougall A. 2021. Combined effect of cell geometry and polarity domains determines the orientation of unequal division. eLife. 10, e75639.","mla":"Godard, Benoit G., et al. “Combined Effect of Cell Geometry and Polarity Domains Determines the Orientation of Unequal Division.” <i>ELife</i>, vol. 10, e75639, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.75639\">10.7554/eLife.75639</a>.","apa":"Godard, B. G., Dumollard, R., Heisenberg, C.-P. J., &#38; Mcdougall, A. (2021). Combined effect of cell geometry and polarity domains determines the orientation of unequal division. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.75639\">https://doi.org/10.7554/eLife.75639</a>"},"intvolume":"        10","external_id":{"isi":["000733610100001"]},"status":"public","file_date_updated":"2022-01-10T09:40:37Z","date_created":"2022-01-09T23:01:26Z","volume":10,"month":"12","oa_version":"Published Version","type":"journal_article","date_updated":"2023-08-17T06:32:44Z","abstract":[{"lang":"eng","text":"Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s)."}],"_id":"10606","year":"2021","acknowledgement":"We thank members of the Heisenberg and McDougall groups for technical advice and discussion. We are grateful to the Bioimaging and Nanofabrication facilities of IST Austria and the Imaging Platform (PIM) and animal facility (CRB) of Institut de la Mer de Villefranche (IMEV), which is supported by EMBRC-France, whose French state funds are managed by the ANR within the Investments of the Future program under reference ANR-10-INBS-0, for continuous support. This work was supported by a collaborative grant from the French Government funding agency Agence National de la Recherche to McDougall (ANR 'MorCell': ANR-17-CE 13-0028) and the Austrian Science Fund to Heisenberg (FWF: I 3601-B27).","quality_controlled":"1","doi":"10.7554/eLife.75639","publication_identifier":{"eissn":["2050-084X"]},"language":[{"iso":"eng"}],"isi":1,"project":[{"call_identifier":"FWF","_id":"2646861A-B435-11E9-9278-68D0E5697425","name":"Control of embryonic cleavage pattern","grant_number":"I03601"}],"article_number":"e75639","title":"Combined effect of cell geometry and polarity domains determines the orientation of unequal division","day":"21","file":[{"date_created":"2022-01-10T09:40:37Z","access_level":"open_access","file_id":"10611","date_updated":"2022-01-10T09:40:37Z","checksum":"759c7a873d554c48a6639e6350746ca6","file_size":7769934,"content_type":"application/pdf","relation":"main_file","creator":"alisjak","file_name":"2021_eLife_Godard.pdf","success":1}],"author":[{"id":"33280250-F248-11E8-B48F-1D18A9856A87","full_name":"Godard, Benoit G","first_name":"Benoit G","last_name":"Godard"},{"last_name":"Dumollard","first_name":"Remi","full_name":"Dumollard, Remi"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg"},{"full_name":"Mcdougall, Alex","first_name":"Alex","last_name":"Mcdougall"}],"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","scopus_import":"1","article_processing_charge":"No","publication":"eLife","department":[{"_id":"CaHe"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications"},{"title":"High potency of sequential therapy with only beta-lactam antibiotics","article_number":"e68876","day":"28","author":[{"full_name":"Batra, Aditi","last_name":"Batra","first_name":"Aditi"},{"last_name":"Römhild","first_name":"Roderich","orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich"},{"last_name":"Rousseau","first_name":"Emilie","full_name":"Rousseau, Emilie"},{"first_name":"Sören","last_name":"Franzenburg","full_name":"Franzenburg, Sören"},{"full_name":"Niemann, Stefan","last_name":"Niemann","first_name":"Stefan"},{"last_name":"Schulenburg","first_name":"Hinrich","full_name":"Schulenburg, Hinrich"}],"scopus_import":"1","article_processing_charge":"No","article_type":"original","publication":"eLife","pmid":1,"department":[{"_id":"CaGu"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","quality_controlled":"1","doi":"10.7554/elife.68876","publication_identifier":{"eissn":["2050-084X"]},"language":[{"iso":"eng"}],"isi":1,"date_created":"2021-07-28T13:36:57Z","volume":10,"abstract":[{"lang":"eng","text":"Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs."}],"date_updated":"2023-08-11T10:26:29Z","oa_version":"Published Version","type":"journal_article","month":"07","_id":"9746","year":"2021","acknowledgement":"We would like to thank Leif Tueffers and João Botelho for discussions and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS, and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further supported by the German Science Foundation Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (project 423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis Kiel (CCGA Kiel).","main_file_link":[{"open_access":"1","url":"https://doi.org/10.7554/eLife.68876"}],"date_published":"2021-07-28T00:00:00Z","oa":1,"publication_status":"published","citation":{"chicago":"Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.68876\">https://doi.org/10.7554/elife.68876</a>.","ieee":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg, “High potency of sequential therapy with only beta-lactam antibiotics,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","short":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg, ELife 10 (2021).","ama":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High potency of sequential therapy with only beta-lactam antibiotics. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.68876\">10.7554/elife.68876</a>","apa":"Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., &#38; Schulenburg, H. (2021). High potency of sequential therapy with only beta-lactam antibiotics. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68876\">https://doi.org/10.7554/elife.68876</a>","mla":"Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” <i>ELife</i>, vol. 10, e68876, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.68876\">10.7554/elife.68876</a>.","ista":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10, e68876."},"intvolume":"        10","external_id":{"pmid":["34318749"],"isi":["000692027800001"]},"status":"public"},{"language":[{"iso":"eng"}],"isi":1,"keyword":["cell delamination","apical constriction","dragging","mechanical forces","collective 18 locomotion","dorsal forerunner cells","zebrafish"],"project":[{"grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation"}],"quality_controlled":"1","doi":"10.7554/eLife.66483","publication_identifier":{"eissn":["2050-084X"]},"article_processing_charge":"Yes","ec_funded":1,"scopus_import":"1","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)"},"publication":"eLife","pmid":1,"department":[{"_id":"CaHe"}],"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism","article_number":"e66483","day":"27","file":[{"file_name":"2021_eLife_Pulgar.pdf","success":1,"file_size":9010446,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_id":"11371","date_updated":"2022-05-13T08:03:37Z","checksum":"a3f82b0499cc822ac1eab48a01f3f57e","date_created":"2022-05-13T08:03:37Z","access_level":"open_access"}],"author":[{"full_name":"Pulgar, Eduardo","first_name":"Eduardo","last_name":"Pulgar"},{"id":"3436488C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5130-2226","full_name":"Schwayer, Cornelia","last_name":"Schwayer","first_name":"Cornelia"},{"last_name":"Guerrero","first_name":"Néstor","full_name":"Guerrero, Néstor"},{"full_name":"López, Loreto","first_name":"Loreto","last_name":"López"},{"full_name":"Márquez, Susana","last_name":"Márquez","first_name":"Susana"},{"first_name":"Steffen","last_name":"Härtel","full_name":"Härtel, Steffen"},{"first_name":"Rodrigo","last_name":"Soto","full_name":"Soto, Rodrigo"},{"full_name":"Heisenberg, Carl Philipp","last_name":"Heisenberg","first_name":"Carl Philipp"},{"first_name":"Miguel L.","last_name":"Concha","full_name":"Concha, Miguel L."}],"citation":{"chicago":"Pulgar, Eduardo, Cornelia Schwayer, Néstor Guerrero, Loreto López, Susana Márquez, Steffen Härtel, Rodrigo Soto, Carl Philipp Heisenberg, and Miguel L. Concha. “Apical Contacts Stemming from Incomplete Delamination Guide Progenitor Cell Allocation through a Dragging Mechanism.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.66483\">https://doi.org/10.7554/eLife.66483</a>.","ieee":"E. Pulgar <i>et al.</i>, “Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","short":"E. Pulgar, C. Schwayer, N. Guerrero, L. López, S. Márquez, S. Härtel, R. Soto, C.P. Heisenberg, M.L. Concha, ELife 10 (2021).","ama":"Pulgar E, Schwayer C, Guerrero N, et al. Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.66483\">10.7554/eLife.66483</a>","apa":"Pulgar, E., Schwayer, C., Guerrero, N., López, L., Márquez, S., Härtel, S., … Concha, M. L. (2021). Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.66483\">https://doi.org/10.7554/eLife.66483</a>","ista":"Pulgar E, Schwayer C, Guerrero N, López L, Márquez S, Härtel S, Soto R, Heisenberg CP, Concha ML. 2021. Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism. eLife. 10, e66483.","mla":"Pulgar, Eduardo, et al. “Apical Contacts Stemming from Incomplete Delamination Guide Progenitor Cell Allocation through a Dragging Mechanism.” <i>ELife</i>, vol. 10, e66483, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.66483\">10.7554/eLife.66483</a>."},"intvolume":"        10","status":"public","external_id":{"isi":["000700428500001"],"pmid":["34448451"]},"ddc":["570"],"date_published":"2021-08-27T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"_id":"9999","year":"2021","date_created":"2021-09-12T22:01:23Z","file_date_updated":"2022-05-13T08:03:37Z","volume":10,"abstract":[{"lang":"eng","text":"The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors’ movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development. Impact Statement: Incomplete delamination serves as a cellular platform for coordinated tissue movements during development, guiding newly formed progenitor cell groups to the differentiation site."}],"date_updated":"2023-08-14T06:53:33Z","month":"08","oa_version":"Published Version","type":"journal_article"},{"status":"public","external_id":{"pmid":["32940606"],"isi":["000584989400001"]},"intvolume":"         9","citation":{"short":"P.J. Gonçalves, J.-M. Lueckmann, M. Deistler, M. Nonnenmacher, K. Öcal, G. Bassetto, C. Chintaluri, W.F. Podlaski, S.A. Haddad, T.P. Vogels, D.S. Greenberg, J.H. Macke, ELife 9 (2020).","chicago":"Gonçalves, Pedro J., Jan-Matthis Lueckmann, Michael Deistler, Marcel Nonnenmacher, Kaan Öcal, Giacomo Bassetto, Chaitanya Chintaluri, et al. “Training Deep Neural Density Estimators to Identify Mechanistic Models of Neural Dynamics.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.56261\">https://doi.org/10.7554/eLife.56261</a>.","ieee":"P. J. Gonçalves <i>et al.</i>, “Training deep neural density estimators to identify mechanistic models of neural dynamics,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","apa":"Gonçalves, P. J., Lueckmann, J.-M., Deistler, M., Nonnenmacher, M., Öcal, K., Bassetto, G., … Macke, J. H. (2020). Training deep neural density estimators to identify mechanistic models of neural dynamics. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.56261\">https://doi.org/10.7554/eLife.56261</a>","ista":"Gonçalves PJ, Lueckmann J-M, Deistler M, Nonnenmacher M, Öcal K, Bassetto G, Chintaluri C, Podlaski WF, Haddad SA, Vogels TP, Greenberg DS, Macke JH. 2020. Training deep neural density estimators to identify mechanistic models of neural dynamics. eLife. 9, e56261.","mla":"Gonçalves, Pedro J., et al. “Training Deep Neural Density Estimators to Identify Mechanistic Models of Neural Dynamics.” <i>ELife</i>, vol. 9, e56261, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.56261\">10.7554/eLife.56261</a>.","ama":"Gonçalves PJ, Lueckmann J-M, Deistler M, et al. Training deep neural density estimators to identify mechanistic models of neural dynamics. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.56261\">10.7554/eLife.56261</a>"},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2020-09-17T00:00:00Z","acknowledgement":"We thank Mahmood S Hoseini and Michael Stryker for sharing their data for Figure 2, and Philipp Berens, Sean Bittner, Jan Boelts, John Cunningham, Richard Gao, Scott Linderman, Eve Marder, Iain Murray, George Papamakarios, Astrid Prinz, Auguste Schulz and Srinivas Turaga for discussions and/or comments on the manuscript. This work was supported by the German Research Foundation (DFG) through SFB 1233 ‘Robust Vision’, (276693517), SFB 1089 ‘Synaptic Microcircuits’, SPP 2041 ‘Computational Connectomics’ and Germany's Excellence Strategy – EXC-Number 2064/1 – Project number 390727645 and the German Federal Ministry of Education and Research (BMBF, project ‘ADIMEM’, FKZ 01IS18052 A-D) to JHM, a Sir Henry Dale Fellowship by the Wellcome Trust and the Royal Society (WT100000; WFP and TPV), a Wellcome Trust Senior Research Fellowship (214316/Z/18/Z; TPV), a ERC Consolidator Grant (SYNAPSEEK; WPF and CC), and a UK Research and Innovation, Biotechnology and Biological Sciences Research Council (CC, UKRI-BBSRC BB/N019512/1). We gratefully acknowledge the Leibniz Supercomputing Centre for funding this project by providing computing time on its Linux-Cluster.","year":"2020","_id":"8127","oa_version":"Published Version","month":"09","type":"journal_article","date_updated":"2023-08-22T07:54:52Z","abstract":[{"text":"Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.","lang":"eng"}],"volume":9,"date_created":"2020-07-16T12:26:04Z","file_date_updated":"2020-10-27T11:37:32Z","project":[{"grant_number":"819603","call_identifier":"H2020","_id":"0aacfa84-070f-11eb-9043-d7eb2c709234","name":"Learning the shape of synaptic plasticity rules for neuronal architectures and function through machine learning."}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.56261","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","department":[{"_id":"TiVo"}],"pmid":1,"publication":"eLife","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)"},"article_processing_charge":"No","scopus_import":"1","ec_funded":1,"author":[{"last_name":"Gonçalves","first_name":"Pedro J.","full_name":"Gonçalves, Pedro J.","orcid":"0000-0002-6987-4836"},{"first_name":"Jan-Matthis","last_name":"Lueckmann","full_name":"Lueckmann, Jan-Matthis","orcid":"0000-0003-4320-4663"},{"first_name":"Michael","last_name":"Deistler","orcid":"0000-0002-3573-0404","full_name":"Deistler, Michael"},{"last_name":"Nonnenmacher","first_name":"Marcel","orcid":"0000-0001-6044-6627","full_name":"Nonnenmacher, Marcel"},{"last_name":"Öcal","first_name":"Kaan","orcid":"0000-0002-8528-6858","full_name":"Öcal, Kaan"},{"full_name":"Bassetto, Giacomo","last_name":"Bassetto","first_name":"Giacomo"},{"first_name":"Chaitanya","last_name":"Chintaluri","orcid":"0000-0003-4252-1608","id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E","full_name":"Chintaluri, Chaitanya"},{"orcid":"0000-0001-6619-7502","full_name":"Podlaski, William F.","first_name":"William F.","last_name":"Podlaski"},{"first_name":"Sara A.","last_name":"Haddad","orcid":"0000-0003-0807-0823","full_name":"Haddad, Sara A."},{"orcid":"0000-0003-3295-6181","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","full_name":"Vogels, Tim P","first_name":"Tim P","last_name":"Vogels"},{"full_name":"Greenberg, David S.","first_name":"David S.","last_name":"Greenberg"},{"full_name":"Macke, Jakob H.","orcid":"0000-0001-5154-8912","last_name":"Macke","first_name":"Jakob H."}],"file":[{"creator":"cziletti","content_type":"application/pdf","relation":"main_file","file_size":17355867,"success":1,"file_name":"2020_eLife_Gonçalves.pdf","access_level":"open_access","date_created":"2020-10-27T11:37:32Z","checksum":"c4300ddcd93ed03fc9c6cdf1f77890be","date_updated":"2020-10-27T11:37:32Z","file_id":"8709"}],"day":"17","article_number":"e56261","title":"Training deep neural density estimators to identify mechanistic models of neural dynamics"},{"quality_controlled":"1","doi":"10.7554/eLife.52067","publication_identifier":{"eissn":["2050-084X"]},"language":[{"iso":"eng"}],"isi":1,"project":[{"grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"},{"name":"Molecular mechanisms of endocytic cargo recognition in plants","_id":"26538374-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03630"}],"article_number":"e52067","title":"Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants","file":[{"date_updated":"2020-07-14T12:47:59Z","file_id":"7494","checksum":"2052daa4be5019534f3a42f200a09f32","date_created":"2020-02-18T07:21:16Z","access_level":"open_access","file_name":"2020_eLife_Narasimhan.pdf","content_type":"application/pdf","relation":"main_file","file_size":7247468,"creator":"dernst"}],"day":"23","author":[{"first_name":"Madhumitha","last_name":"Narasimhan","orcid":"0000-0002-8600-0671","id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","full_name":"Narasimhan, Madhumitha"},{"first_name":"Alexander J","last_name":"Johnson","orcid":"0000-0002-2739-8843","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","full_name":"Johnson, Alexander J"},{"id":"4456104E-F248-11E8-B48F-1D18A9856A87","full_name":"Prizak, Roshan","last_name":"Prizak","first_name":"Roshan"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter"},{"id":"2DE75584-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0471-8285","full_name":"Tan, Shutang","last_name":"Tan","first_name":"Shutang"},{"first_name":"Barbara E","last_name":"Casillas Perez","id":"351ED2AA-F248-11E8-B48F-1D18A9856A87","full_name":"Casillas Perez, Barbara E"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","last_name":"Friml","first_name":"Jiří"}],"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)"},"article_processing_charge":"No","scopus_import":"1","ec_funded":1,"publication":"eLife","department":[{"_id":"JiFr"},{"_id":"GaTk"},{"_id":"EM-Fac"},{"_id":"SyCr"}],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"ddc":["570","580"],"date_published":"2020-01-23T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"ama":"Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>","mla":"Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>, vol. 9, e52067, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>.","ista":"Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE, Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 9, e52067.","apa":"Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas Perez, B. E., &#38; Friml, J. (2020). Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>","ieee":"M. Narasimhan <i>et al.</i>, “Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","chicago":"Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann, Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>.","short":"M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas Perez, J. Friml, ELife 9 (2020)."},"intvolume":"         9","external_id":{"pmid":["31971511"],"isi":["000514104100001"]},"status":"public","date_created":"2020-02-16T23:00:50Z","file_date_updated":"2020-07-14T12:47:59Z","volume":9,"type":"journal_article","month":"01","oa_version":"Published Version","abstract":[{"lang":"eng","text":"In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes."}],"date_updated":"2023-08-18T06:33:07Z","_id":"7490","year":"2020"},{"publication_identifier":{"eissn":["2050-084X"]},"quality_controlled":"1","doi":"10.7554/elife.30674","language":[{"iso":"eng"}],"file":[{"file_name":"2017_eLife_Lyons.pdf","success":1,"creator":"cziletti","file_size":1603102,"content_type":"application/pdf","relation":"main_file","checksum":"4cfcdd67511ae4aed3d993550e46e146","file_id":"9446","date_updated":"2021-06-02T14:33:36Z","access_level":"open_access","date_created":"2021-06-02T14:33:36Z"}],"day":"15","author":[{"full_name":"Lyons, David B","last_name":"Lyons","first_name":"David B"},{"orcid":"0000-0002-0123-8649","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","full_name":"Zilberman, Daniel","last_name":"Zilberman","first_name":"Daniel"}],"article_number":"e30674","title":"DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes","department":[{"_id":"DaZi"}],"pmid":1,"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","publisher":"eLife Sciences Publications","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)"},"article_processing_charge":"No","scopus_import":"1","publication":"eLife","has_accepted_license":"1","publication_status":"published","oa":1,"ddc":["570"],"date_published":"2017-11-15T00:00:00Z","external_id":{"pmid":["29140247"]},"status":"public","citation":{"ama":"Lyons DB, Zilberman D. DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/elife.30674\">10.7554/elife.30674</a>","ista":"Lyons DB, Zilberman D. 2017. DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes. eLife. 6, e30674.","mla":"Lyons, David B., and Daniel Zilberman. “DDM1 and Lsh Remodelers Allow Methylation of DNA Wrapped in Nucleosomes.” <i>ELife</i>, vol. 6, e30674, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/elife.30674\">10.7554/elife.30674</a>.","apa":"Lyons, D. B., &#38; Zilberman, D. (2017). DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.30674\">https://doi.org/10.7554/elife.30674</a>","ieee":"D. B. Lyons and D. Zilberman, “DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","chicago":"Lyons, David B, and Daniel Zilberman. “DDM1 and Lsh Remodelers Allow Methylation of DNA Wrapped in Nucleosomes.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/elife.30674\">https://doi.org/10.7554/elife.30674</a>.","short":"D.B. Lyons, D. Zilberman, ELife 6 (2017)."},"intvolume":"         6","extern":"1","oa_version":"Published Version","month":"11","type":"journal_article","abstract":[{"lang":"eng","text":"Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation."}],"date_updated":"2021-12-14T07:54:36Z","file_date_updated":"2021-06-02T14:33:36Z","date_created":"2021-06-02T14:28:58Z","volume":6,"year":"2017","_id":"9445"}]