[{"abstract":[{"lang":"eng","text":"With the advent of optogenetics, it became possible to change the activity of a targeted population of neurons in a temporally controlled manner. To combine the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics, we have developed a closed-loop recording system that allows for the actual electrophysiological signal to be used as a trigger for the laser light mediating the optogenetic intervention. We have optimized the weight, size, and shape of the corresponding implant to make it compatible with the size, force, and movements of a behaving mouse, and we have shown that the system can efficiently block sharp wave ripple (SWR) events using those events themselves as a trigger. To demonstrate the full potential of the optogenetic recording system we present a pilot study addressing the contribution of SWR events to learning in a complex behavioral task."}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 5","month":"07","publication_status":"published","language":[{"iso":"eng"}],"file":[{"creator":"dernst","date_updated":"2020-07-14T12:47:13Z","file_size":3746884,"date_created":"2019-02-05T12:48:36Z","file_name":"2018_ENeuro_Guerrero.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"5921","checksum":"f4915d45fc7ad4648b7b7a13fdecca01"}],"ec_funded":1,"issue":"4","volume":5,"related_material":{"record":[{"relation":"dissertation_contains","id":"6849","status":"public"}]},"_id":"5914","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","status":"public","date_updated":"2024-03-27T23:30:10Z","ddc":["570"],"department":[{"_id":"JoCs"}],"file_date_updated":"2020-07-14T12:47:13Z","oa":1,"publisher":"Society of Neuroscience","quality_controlled":"1","year":"2018","isi":1,"has_accepted_license":"1","publication":"eNeuro","day":"27","date_created":"2019-02-03T22:59:16Z","doi":"10.1523/ENEURO.0087-18.2018","date_published":"2018-07-27T00:00:00Z","article_number":"e0087","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"grant_number":"I2072-B27","name":"Interneuron plasticity during spatial learning","_id":"257D4372-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"citation":{"short":"D.K. Rangel Guerrero, J.G. Donnett, J.L. Csicsvari, K. Kovács, ENeuro 5 (2018).","ieee":"D. K. Rangel Guerrero, J. G. Donnett, J. L. Csicsvari, and K. Kovács, “Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning,” eNeuro, vol. 5, no. 4. Society of Neuroscience, 2018.","ama":"Rangel Guerrero DK, Donnett JG, Csicsvari JL, Kovács K. Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning. eNeuro. 2018;5(4). doi:10.1523/ENEURO.0087-18.2018","apa":"Rangel Guerrero, D. K., Donnett, J. G., Csicsvari, J. L., & Kovács, K. (2018). Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning. ENeuro. Society of Neuroscience. https://doi.org/10.1523/ENEURO.0087-18.2018","mla":"Rangel Guerrero, Dámaris K., et al. “Tetrode Recording from the Hippocampus of Behaving Mice Coupled with Four-Point-Irradiation Closed-Loop Optogenetics: A Technique to Study the Contribution of Hippocampal SWR Events to Learning.” ENeuro, vol. 5, no. 4, e0087, Society of Neuroscience, 2018, doi:10.1523/ENEURO.0087-18.2018.","ista":"Rangel Guerrero DK, Donnett JG, Csicsvari JL, Kovács K. 2018. Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning. eNeuro. 5(4), e0087.","chicago":"Rangel Guerrero, Dámaris K, James G. Donnett, Jozsef L Csicsvari, and Krisztián Kovács. “Tetrode Recording from the Hippocampus of Behaving Mice Coupled with Four-Point-Irradiation Closed-Loop Optogenetics: A Technique to Study the Contribution of Hippocampal SWR Events to Learning.” ENeuro. Society of Neuroscience, 2018. https://doi.org/10.1523/ENEURO.0087-18.2018."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000443994700007"]},"article_processing_charge":"No","author":[{"orcid":"0000-0002-8602-4374","full_name":"Rangel Guerrero, Dámaris K","last_name":"Rangel Guerrero","first_name":"Dámaris K","id":"4871BCE6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Donnett","full_name":"Donnett, James G.","first_name":"James G."},{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari"},{"full_name":"Kovács, Krisztián","orcid":"0000-0001-6251-1007","last_name":"Kovács","id":"2AB5821E-F248-11E8-B48F-1D18A9856A87","first_name":"Krisztián"}],"title":"Tetrode recording from the hippocampus of behaving mice coupled with four-point-irradiation closed-loop optogenetics: A technique to study the contribution of Hippocampal SWR events to learning"},{"date_updated":"2024-03-27T23:30:09Z","department":[{"_id":"MiSi"}],"_id":"402","status":"public","type":"journal_article","article_type":"original","language":[{"iso":"eng"}],"publication_status":"published","ec_funded":1,"volume":359,"issue":"6382","related_material":{"record":[{"relation":"dissertation_contains","id":"6947","status":"public"}]},"pmid":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"}],"abstract":[{"lang":"eng","text":"During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined."}],"intvolume":" 359","month":"03","main_file_link":[{"url":"https://doi.org/10.1126/science.aal3662","open_access":"1"}],"scopus_import":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Brown M, Assen FP, Leithner AF, et al. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 2018;359(6382):1408-1411. doi:10.1126/science.aal3662","apa":"Brown, M., Assen, F. P., Leithner, A. F., Abe, J., Schachner, H., Asfour, G., … Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aal3662","short":"M. Brown, F.P. Assen, A.F. Leithner, J. Abe, H. Schachner, G. Asfour, Z. Bagó Horváth, J. Stein, P. Uhrin, M.K. Sixt, D. Kerjaschki, Science 359 (2018) 1408–1411.","ieee":"M. Brown et al., “Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice,” Science, vol. 359, no. 6382. American Association for the Advancement of Science, pp. 1408–1411, 2018.","mla":"Brown, Markus, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science, vol. 359, no. 6382, American Association for the Advancement of Science, 2018, pp. 1408–11, doi:10.1126/science.aal3662.","ista":"Brown M, Assen FP, Leithner AF, Abe J, Schachner H, Asfour G, Bagó Horváth Z, Stein J, Uhrin P, Sixt MK, Kerjaschki D. 2018. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 359(6382), 1408–1411.","chicago":"Brown, Markus, Frank P Assen, Alexander F Leithner, Jun Abe, Helga Schachner, Gabriele Asfour, Zsuzsanna Bagó Horváth, et al. “Lymph Node Blood Vessels Provide Exit Routes for Metastatic Tumor Cell Dissemination in Mice.” Science. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/science.aal3662."},"title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","article_processing_charge":"No","external_id":{"isi":["000428043600047"],"pmid":["29567714"]},"publist_id":"7428","author":[{"full_name":"Brown, Markus","last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus"},{"id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","first_name":"Frank P","last_name":"Assen","orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P"},{"last_name":"Leithner","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F"},{"full_name":"Abe, Jun","last_name":"Abe","first_name":"Jun"},{"last_name":"Schachner","full_name":"Schachner, Helga","first_name":"Helga"},{"first_name":"Gabriele","last_name":"Asfour","full_name":"Asfour, Gabriele"},{"last_name":"Bagó Horváth","full_name":"Bagó Horváth, Zsuzsanna","first_name":"Zsuzsanna"},{"last_name":"Stein","full_name":"Stein, Jens","first_name":"Jens"},{"first_name":"Pavel","last_name":"Uhrin","full_name":"Uhrin, Pavel"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt"},{"last_name":"Kerjaschki","full_name":"Kerjaschki, Dontscho","first_name":"Dontscho"}],"project":[{"name":"Cytoskeletal force generation and transduction of leukocytes (FWF)","grant_number":"Y 564-B12","call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425"},{"grant_number":"281556","name":"Cytoskeletal force generation and force transduction of migrating leukocytes (EU)","_id":"25A603A2-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"publication":"Science","day":"23","year":"2018","isi":1,"date_created":"2018-12-11T11:46:16Z","date_published":"2018-03-23T00:00:00Z","doi":"10.1126/science.aal3662","page":"1408 - 1411","acknowledgement":"M.B. was supported by the Cell Communication in Health and Disease graduate study program of the Austrian Science Fund (FWF) and the Medical University of Vienna. M.S. was supported by the European Research Council (grant ERC GA 281556) and an FWF START award.\r\nWe thank C. Moussion for establishing the intralymphatic injection at IST Austria and for providing anti-PNAd hybridoma supernatant, R. Förster and A. Braun for sharing the intralymphatic injection technology, K. Vaahtomeri for the lentiviral constructs, M. Hons for establishing in vivo multiphoton imaging, the Sixt lab for intellectual input, M. Schunn for help with the design of the in vivo experiments, F. Langer for technical assistance with the in vivo experiments, the bioimaging facility of IST Austria for support, and R. Efferl for providing the CT26 cell line.","oa":1,"publisher":"American Association for the Advancement of Science","quality_controlled":"1"},{"file_date_updated":"2021-02-11T23:30:15Z","department":[{"_id":"GaNo"}],"ddc":["570","616"],"date_updated":"2023-09-07T12:38:59Z","supervisor":[{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"pubrep_id":"992","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","_id":"395","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1183"}]},"language":[{"iso":"eng"}],"file":[{"creator":"dernst","file_size":43684035,"date_updated":"2021-02-11T23:30:15Z","file_name":"2018_Thesis_Tarlungeanu_source.docx","date_created":"2019-04-05T09:19:17Z","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"6217","checksum":"9f5231c96e0ad945040841a8630232da"},{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"0c33c370aa2010df5c552db57a6d01e9","file_id":"6218","embargo":"2018-03-15","date_updated":"2021-02-11T11:17:16Z","file_size":30511532,"creator":"dernst","date_created":"2019-04-05T09:19:17Z","file_name":"2018_Thesis_Tarlungeanu.pdf"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"month":"03","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"}],"abstract":[{"text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. ","lang":"eng"}],"title":"The branched chain amino acids in autism spectrum disorders ","article_processing_charge":"No","author":[{"full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu","first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"7434","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.","ista":"Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria.","mla":"Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.","ieee":"D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018.","short":"D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018.","ama":"Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:10.15479/AT:ISTA:th_992","apa":"Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992"},"project":[{"_id":"25473368-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523"}],"date_created":"2018-12-11T11:46:14Z","doi":"10.15479/AT:ISTA:th_992","date_published":"2018-03-01T00:00:00Z","page":"88","day":"01","year":"2018","has_accepted_license":"1","oa":1,"publisher":"Institute of Science and Technology Austria"},{"doi":"10.15479/AT:ISTA:th_1032","date_published":"2018-06-27T00:00:00Z","date_created":"2018-12-11T11:44:22Z","page":"186","day":"27","has_accepted_license":"1","year":"2018","publisher":"Institute of Science and Technology Austria","oa":1,"title":"From the left to the right: A tale of asymmetries, environments, and hippocampal development","publist_id":"8003","author":[{"first_name":"Matthew J","id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Case, Matthew J","last_name":"Case"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Case, Matthew J. From the Left to the Right: A Tale of Asymmetries, Environments, and Hippocampal Development. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_1032.","apa":"Case, M. J. (2018). From the left to the right: A tale of asymmetries, environments, and hippocampal development. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_1032","ama":"Case MJ. From the left to the right: A tale of asymmetries, environments, and hippocampal development. 2018. doi:10.15479/AT:ISTA:th_1032","short":"M.J. Case, From the Left to the Right: A Tale of Asymmetries, Environments, and Hippocampal Development, Institute of Science and Technology Austria, 2018.","ieee":"M. J. Case, “From the left to the right: A tale of asymmetries, environments, and hippocampal development,” Institute of Science and Technology Austria, 2018.","chicago":"Case, Matthew J. “From the Left to the Right: A Tale of Asymmetries, Environments, and Hippocampal Development.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_1032.","ista":"Case MJ. 2018. From the left to the right: A tale of asymmetries, environments, and hippocampal development. Institute of Science and Technology Austria."},"related_material":{"record":[{"status":"public","id":"682","relation":"part_of_dissertation"}]},"file":[{"creator":"dernst","date_updated":"2021-02-11T23:30:13Z","file_size":141270528,"date_created":"2019-04-09T07:16:26Z","file_name":"2018_Thesis_Case_Source.doc","access_level":"closed","relation":"source_file","content_type":"application/msword","embargo_to":"open_access","checksum":"dcc7b55619d8509dd62b8e99d6cdee44","file_id":"6251"},{"date_created":"2019-04-09T07:16:23Z","file_name":"2018_Thesis_Case.pdf","creator":"dernst","date_updated":"2021-02-11T11:17:14Z","file_size":15193621,"checksum":"f69fdd5c8709c4e618aa8c1a1221153d","file_id":"6252","embargo":"2019-07-05","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","month":"06","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Asymmetries have long been known about in the central nervous system. From gross anatomical differences, such as the presence of the parapineal organ in only one hemisphere of the developing zebrafish, to more subtle differences in activity between both hemispheres, as seen in freely roaming animals or human participants under PET and fMRI imaging analysis. The presence of asymmetries has been demonstrated to have huge behavioural implications, with their disruption often leading to the generation of neurological disorders, memory problems, changes in personality, and in an organism's health and well-being. For my Ph.D. work I aimed to tackle two important avenues of research. The first being the process of input-side dependency in the hippocampus, with the goal of finding a key gene responsible for its development (Gene X). The second project was to do with experience-induced laterality formation in the hippocampus. Specifically, how laterality in the synapse density of the CA1 stratum radiatum (s.r.) could be induced purely through environmental enrichment. Through unilateral tracer injections into the CA3, I was able to selectively measure the properties of synapses within the CA1 and investigate how they differed based upon which hemisphere the presynaptic neurone originated. Having found the existence of a previously unreported reversed (left-isomerism) i.v. mutant, through morpholocal examination of labelled terminals in the CA1 s.r., I aimed to elucidate a key gene responsible for the process of left or right determination of inputs to the CA1 s.r.. This work relates to the previous finding of input-side dependent asymmetry in the wild-type rodent, where the origin of the projecting neurone to the CA1 will determine the morphology of a synapse, to a greater degree than the hemisphere in which the projection terminates. Using left- and right-isomerism i.v. mice, in combination with whole genome sequence analysis, I highlight Ena/VASP-like (Evl) as a potential target for Gene X. In relation to this topic, I also highlight my work in the recently published paper of how knockout of PirB can lead to a lack of input-side dependency in the murine hippocampus. For the second question, I show that the environmental enrichment paradigm will lead to an asymmetry in the synapse densities in the hippocampus of mice. I also highlight that the nature of the enrichment is of less consequence than the process of enrichment itself. I demonstrate that the CA3 region will dramatically alter its projection targets, in relation to environmental stimulation, with the asymmetry in synaptic density, caused by enrichment, relying heavily on commissural fibres. I also highlight the vital importance of input-side dependent asymmetry, as a necessary component of experience-dependent laterality formation in the CA1 s.r.. However, my results suggest that it isn't the only cause, as there appears to be a CA1 dependent mechanism also at play. Upon further investigation, I highlight the significant, and highly important, finding that the changes seen in the CA1 s.r. were predominantly caused through projections from the left-CA3, with the right-CA3 having less involvement in this mechanism."}],"file_date_updated":"2021-02-11T23:30:13Z","department":[{"_id":"RySh"}],"ddc":["571","576"],"supervisor":[{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"}],"date_updated":"2023-09-07T12:39:22Z","status":"public","pubrep_id":"1032","type":"dissertation","_id":"51"},{"month":"11","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Genomic imprinting is an epigenetic process that leads to parent of origin-specific gene expression in a subset of genes. Imprinted genes are essential for brain development, and deregulation of imprinting is associated with neurodevelopmental diseases and the pathogenesis of psychiatric disorders. However, the cell-type specificity of imprinting at single cell resolution, and how imprinting and thus gene dosage regulates neuronal circuit assembly is still largely unknown. Here, MADM (Mosaic Analysis with Double Markers) technology was employed to assess genomic imprinting at single cell level. By visualizing MADM-induced uniparental disomies (UPDs) in distinct colors at single cell level in genetic mosaic animals, this experimental paradigm provides a unique quantitative platform to systematically assay the UPD-mediated imbalances in imprinted gene expression at unprecedented resolution. An experimental pipeline based on FACS, RNA-seq and bioinformatics analysis was established and applied to systematically map cell-type-specific ‘imprintomes’ in the mouse brain. The results revealed that parental-specific expression of imprinted genes per se is rarely cell-type-specific even at the individual cell level. Conversely, when we extended the comparison to downstream responses resulting from imbalanced imprinted gene expression, we discovered an unexpectedly high degree of cell-type specificity. Furthermore, we determined a novel function of genomic imprinting in cortical astrocyte production and in olfactory bulb (OB) granule cell generation. These results suggest important functional implication of genomic imprinting for generating cell-type diversity in the brain. In addition, MADM provides a powerful tool to study candidate genes by concomitant genetic manipulation and fluorescent labelling of single cells. MADM-based candidate gene approach was utilized to identify potential imprinted genes involved in the generation of cortical astrocytes and OB granule cells. We investigated p57Kip2, a maternally expressed gene and known cell cycle regulator. Although we found that p57Kip2 does not play a role in these processes, we detected an unexpected function of the paternal allele previously thought to be silent. Finally, we took advantage of a key property of MADM which is to allow unambiguous investigation of environmental impact on single cells. The experimental pipeline based on FACS and RNA-seq analysis of MADM-labeled cells was established to probe the functional differences of single cell loss of gene function compared to global loss of function on a transcriptional level. With this method, both common and distinct responses were isolated due to cell-autonomous and non-autonomous effects acting on genotypically identical cells. As a result, transcriptional changes were identified which result solely from the surrounding environment. Using the MADM technology to study genomic imprinting at single cell resolution, we have identified cell-type-specific gene expression, novel gene function and the impact of environment on single cell transcriptomes. Together, these provide important insights to the understanding of mechanisms regulating cell-type specificity and thus diversity in the brain."}],"file":[{"file_size":17949175,"date_updated":"2019-11-23T23:30:03Z","creator":"dernst","file_name":"Thesis_LaukoterSusanne_FINAL.docx","date_created":"2019-05-10T07:47:04Z","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","file_id":"6396","checksum":"41fdbf5fdce312802935d88a8ad9932c"},{"embargo":"2019-11-21","checksum":"53001a9a0c9e570e598d861bb0af28aa","file_id":"6397","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"Thesis_LaukoterSusanne_FINAL.pdf","date_created":"2019-05-10T07:47:04Z","file_size":21187245,"date_updated":"2021-02-11T11:17:16Z","creator":"dernst"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","status":"public","pubrep_id":"1057","type":"dissertation","_id":"10","file_date_updated":"2021-02-11T11:17:16Z","department":[{"_id":"SiHi"}],"ddc":["570"],"supervisor":[{"first_name":"Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","full_name":"Vicoso, Beatriz","orcid":"0000-0002-4579-8306","last_name":"Vicoso"}],"date_updated":"2023-09-07T12:40:44Z","publisher":"Institute of Science and Technology Austria","oa":1,"doi":"10.15479/AT:ISTA:th1057","date_published":"2018-11-21T00:00:00Z","date_created":"2018-12-11T11:44:08Z","page":"1 - 139","day":"21","has_accepted_license":"1","year":"2018","title":"Role of genomic imprinting in cerebral cortex development","author":[{"last_name":"Laukoter","full_name":"Laukoter, Susanne","orcid":"0000-0002-7903-3010","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"8046","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Laukoter, Susanne. “Role of Genomic Imprinting in Cerebral Cortex Development.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1057.","ista":"Laukoter S. 2018. Role of genomic imprinting in cerebral cortex development. Institute of Science and Technology Austria.","mla":"Laukoter, Susanne. Role of Genomic Imprinting in Cerebral Cortex Development. Institute of Science and Technology Austria, 2018, pp. 1–139, doi:10.15479/AT:ISTA:th1057.","apa":"Laukoter, S. (2018). Role of genomic imprinting in cerebral cortex development. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1057","ama":"Laukoter S. Role of genomic imprinting in cerebral cortex development. 2018:1-139. doi:10.15479/AT:ISTA:th1057","ieee":"S. Laukoter, “Role of genomic imprinting in cerebral cortex development,” Institute of Science and Technology Austria, 2018.","short":"S. Laukoter, Role of Genomic Imprinting in Cerebral Cortex Development, Institute of Science and Technology Austria, 2018."}},{"date_created":"2018-12-11T11:45:49Z","doi":"10.15479/AT:ISTA:th_998","date_published":"2018-04-12T00:00:00Z","page":"99","day":"12","year":"2018","has_accepted_license":"1","oa":1,"publisher":"Institute of Science and Technology Austria","acknowledgement":"First of all I would like to thank Michael Sixt for giving me the opportunity to work in \r\nhis group and for his support throughout the years. He is a truly inspiring person and \r\nthe best boss one can imagine. I would also like to thank all current and past \r\nmembers of the Sixt group for their help and the great working atmosphere in the lab. \r\nIt is a true privilege to work with such a bright, funny and friendly group of people and \r\nI’m proud that I could be part of it. Furthermore, I would like to say ‘thank you’ to Daria Siekhaus for all the meetings and discussion we had throughout the years \r\nand to Federica Benvenuti for being part of my committee. I am also grateful to Jack \r\nMerrin in the nanofabrication facility and all the people working in the bioimaging-\r\n, the electron microscopy- and the preclinical facilities.","title":"Branched actin networks in dendritic cell biology","article_processing_charge":"No","author":[{"last_name":"Leithner","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F"}],"publist_id":"7542","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_998.","ista":"Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria.","mla":"Leithner, Alexander F. Branched Actin Networks in Dendritic Cell Biology. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_998.","ama":"Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:10.15479/AT:ISTA:th_998","apa":"Leithner, A. F. (2018). Branched actin networks in dendritic cell biology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_998","short":"A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute of Science and Technology Austria, 2018.","ieee":"A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute of Science and Technology Austria, 2018."},"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1321"}]},"language":[{"iso":"eng"}],"file":[{"creator":"dernst","file_size":29027671,"date_updated":"2021-02-11T23:30:17Z","file_name":"PhD_thesis_AlexLeithner_final_version.docx","date_created":"2019-04-05T09:23:11Z","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"d5e3edbac548c26c1fa43a4b37a54a4c","file_id":"6219"},{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","embargo":"2019-04-15","checksum":"071f7476db29e41146824ebd0697cb10","file_id":"6220","file_size":66045341,"date_updated":"2021-02-11T11:17:16Z","creator":"dernst","file_name":"PhD_thesis_AlexLeithner.pdf","date_created":"2019-04-05T09:23:11Z"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"month":"04","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"In the here presented thesis, we explore the role of branched actin networks in cell migration and antigen presentation, the two most relevant processes in dendritic cell biology. Branched actin networks construct lamellipodial protrusions at the leading edge of migrating cells. These are typically seen as adhesive structures, which mediate force transduction to the extracellular matrix that leads to forward locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found that the resulting cells lack lamellipodial protrusions. Instead, depending on the maturation state, one or multiple filopodia were formed. By challenging these cells in a variety of migration assays we found that lamellipodial protrusions are dispensable for the locomotion of leukocytes and actually dampen the speed of migration. However, lamellipodia are critically required to negotiate complex environments that DCs experience while they travel to the next draining lymph node. Taken together our results suggest that leukocyte lamellipodia have rather a sensory- than a force transducing function. Furthermore, we show for the first time structure and dynamics of dendritic cell F-actin at the immunological synapse with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension, leading to an altered ultrastructure of the immunological synapse and severe T cell priming defects. These results point towards a previously unappreciated role of the cellular mechanics of dendritic cells in T cell activation. Additionally, we present a novel cell culture based system for the differentiation of dendritic cells from conditionally immortalized hematopoietic precursors. These precursor cells are genetically tractable via the CRISPR/Cas9 system while they retain their ability to differentiate into highly migratory dendritic cells and other immune cells. This will foster the study of all aspects of dendritic cell biology and beyond. "}],"acknowledged_ssus":[{"_id":"NanoFab"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"department":[{"_id":"MiSi"}],"file_date_updated":"2021-02-11T23:30:17Z","ddc":["571","599","610"],"date_updated":"2023-09-07T12:39:44Z","supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"pubrep_id":"998","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","_id":"323"},{"title":"Identification and characterization of novel auxin-cytokinin cross-talk components","publist_id":"7277","author":[{"full_name":"Hurny, Andrej","orcid":"0000-0003-3638-1426","last_name":"Hurny","id":"4DC4AF46-F248-11E8-B48F-1D18A9856A87","first_name":"Andrej"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Hurny, Andrej. “Identification and Characterization of Novel Auxin-Cytokinin Cross-Talk Components.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_930.","ista":"Hurny A. 2018. Identification and characterization of novel auxin-cytokinin cross-talk components. Institute of Science and Technology Austria.","mla":"Hurny, Andrej. Identification and Characterization of Novel Auxin-Cytokinin Cross-Talk Components. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_930.","ieee":"A. Hurny, “Identification and characterization of novel auxin-cytokinin cross-talk components,” Institute of Science and Technology Austria, 2018.","short":"A. Hurny, Identification and Characterization of Novel Auxin-Cytokinin Cross-Talk Components, Institute of Science and Technology Austria, 2018.","apa":"Hurny, A. (2018). Identification and characterization of novel auxin-cytokinin cross-talk components. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_930","ama":"Hurny A. Identification and characterization of novel auxin-cytokinin cross-talk components. 2018. doi:10.15479/AT:ISTA:th_930"},"publisher":"Institute of Science and Technology Austria","oa":1,"date_published":"2018-01-01T00:00:00Z","doi":"10.15479/AT:ISTA:th_930","date_created":"2018-12-11T11:47:03Z","page":"147","day":"01","has_accepted_license":"1","year":"2018","status":"public","pubrep_id":"930","type":"dissertation","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)"},"_id":"539","department":[{"_id":"EvBe"}],"file_date_updated":"2020-12-02T23:30:08Z","ddc":["570"],"supervisor":[{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","first_name":"Eva","last_name":"Benková","full_name":"Benková, Eva","orcid":"0000-0002-8510-9739"}],"date_updated":"2023-09-07T12:41:06Z","month":"01","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"The whole life cycle of plants as well as their responses to environmental stimuli is governed by a complex network of hormonal regulations. A number of studies have demonstrated an essential role of both auxin and cytokinin in the regulation of many aspects of plant growth and development including embryogenesis, postembryonic organogenic processes such as root, and shoot branching, root and shoot apical meristem activity and phyllotaxis. Over the last decades essential knowledge on the key molecular factors and pathways that spatio-temporally define auxin and cytokinin activities in the plant body has accumulated. However, how both hormonal pathways are interconnected by a complex network of interactions and feedback circuits that determines the final outcome of the individual hormone actions is still largely unknown. Root system architecture establishment and in particular formation of lateral organs is prime example of developmental process at whose regulation both auxin and cytokinin pathways converge. To dissect convergence points and pathways that tightly balance auxin - cytokinin antagonistic activities that determine the root branching pattern transcriptome profiling was applied. Genome wide expression analyses of the xylem pole pericycle, a tissue giving rise to lateral roots, led to identification of genes that are highly responsive to combinatorial auxin and cytokinin treatments and play an essential function in the auxin-cytokinin regulated root branching. SYNERGISTIC AUXIN CYTOKININ 1 (SYAC1) gene, which encodes for a protein of unknown function, was detected among the top candidate genes of which expression was synergistically up-regulated by simultaneous hormonal treatment. Plants with modulated SYAC1 activity exhibit severe defects in the root system establishment and attenuate developmental responses to both auxin and cytokinin. To explore the biological function of the SYAC1, we employed different strategies including expression pattern analysis, subcellular localization and phenotypic analyses of the syac1 loss-of-function and gain-of-function transgenic lines along with the identification of the SYAC1 interaction partners. Detailed functional characterization revealed that SYAC1 acts as a developmentally specific regulator of the secretory pathway to control deposition of cell wall components and thereby rapidly fine tune elongation growth.","lang":"eng"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"1024","status":"public"}]},"file":[{"file_size":28112114,"date_updated":"2020-12-02T23:30:08Z","creator":"dernst","file_name":"2018_Hurny_thesis_source.docx","date_created":"2019-04-05T09:37:56Z","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","file_id":"6226","checksum":"0c9d6d1c80d9857e6e545213467bbcb2"},{"date_created":"2019-04-05T09:37:55Z","file_name":"2018_Hurny_thesis.pdf","creator":"dernst","date_updated":"2020-12-02T09:52:16Z","file_size":12524427,"file_id":"6227","checksum":"ecbe481a1413d270bd501b872c7ed54f","embargo":"2019-07-10","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD"},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Gridchyn I. Reactivation content is important for consolidation of spatial memory. 2018. doi:10.15479/AT:ISTA:th_1042","apa":"Gridchyn, I. (2018). Reactivation content is important for consolidation of spatial memory. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_1042","ieee":"I. Gridchyn, “Reactivation content is important for consolidation of spatial memory,” Institute of Science and Technology Austria, 2018.","short":"I. Gridchyn, Reactivation Content Is Important for Consolidation of Spatial Memory, Institute of Science and Technology Austria, 2018.","mla":"Gridchyn, Igor. Reactivation Content Is Important for Consolidation of Spatial Memory. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_1042.","ista":"Gridchyn I. 2018. Reactivation content is important for consolidation of spatial memory. Institute of Science and Technology Austria.","chicago":"Gridchyn, Igor. “Reactivation Content Is Important for Consolidation of Spatial Memory.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_1042."},"title":"Reactivation content is important for consolidation of spatial memory","author":[{"first_name":"Igor","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1807-1929","full_name":"Gridchyn, Igor","last_name":"Gridchyn"}],"publist_id":"8006","article_processing_charge":"No","day":"27","has_accepted_license":"1","year":"2018","date_published":"2018-08-27T00:00:00Z","doi":"10.15479/AT:ISTA:th_1042","date_created":"2018-12-11T11:44:21Z","page":"104","publisher":"Institute of Science and Technology Austria","oa":1,"ddc":["573"],"supervisor":[{"first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L"}],"date_updated":"2023-09-07T12:42:44Z","file_date_updated":"2021-02-11T23:30:22Z","department":[{"_id":"JoCs"}],"_id":"48","status":"public","pubrep_id":"1042","type":"dissertation","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)"},"file":[{"access_level":"closed","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","file_id":"6236","checksum":"7db4415e435590fa33542c7b0a0321d7","creator":"dernst","date_updated":"2021-02-11T23:30:22Z","file_size":7666687,"date_created":"2019-04-08T13:36:01Z","file_name":"2018_Thesis_Gridchyn_source.docx"},{"file_name":"2018_Thesis_Gridchyn.pdf","date_created":"2019-04-08T13:36:01Z","creator":"dernst","file_size":6034153,"date_updated":"2021-02-11T11:17:18Z","embargo":"2019-08-29","file_id":"6237","checksum":"f96f3fe8979f7b1e6db6acaca962b10c","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The hippocampus is a key brain region for spatial memory and navigation and is needed at all stages of memory, including encoding, consolidation, and recall. Hippocampal place cells selectively discharge at specific locations of the environment to form a cognitive map of the space. During the rest period and sleep following spatial navigation and/or learning, the waking activity of the place cells is reactivated within high synchrony events. This reactivation is thought to be important for memory consolidation and stabilization of the spatial representations. The aim of my thesis was to directly test whether the reactivation content encoded in firing patterns of place cells is important for consolidation of spatial memories. In particular, I aimed to test whether, in cases when multiple spatial memory traces are acquired during learning, the specific disruption of the reactivation of a subset of these memories leads to the selective disruption of the corresponding memory traces or through memory interference the other learned memories are disrupted as well. In this thesis, using a modified cheeseboard paradigm and a closed-loop recording setup with feedback optogenetic stimulation, I examined how the disruption of the reactivation of specific spiking patterns affects consolidation of the corresponding memory traces. To obtain multiple distinctive memories, animals had to perform a spatial task in two distinct cheeseboard environments and the reactivation of spiking patterns associated with one of the environments (target) was disrupted after learning during four hours rest period using a real-time decoding method. This real-time decoding method was capable of selectively affecting the firing rates and cofiring correlations of the target environment-encoding cells. The selective disruption led to behavioural impairment in the memory tests after the rest periods in the target environment but not in the other undisrupted control environment. In addition, the map of the target environment was less stable in the impaired memory tests compared to the learning session before than the map of the control environment. However, when the animal relearned the task, the same map recurred in the target environment that was present during learning before the disruption. Altogether my work demonstrated that the reactivation content is important: assembly-related disruption of reactivation can lead to a selective memory impairment and deficiency in map stability. These findings indeed suggest that reactivated assembly patterns reflect processes associated with the consolidation of memory traces. "}],"month":"08","alternative_title":["ISTA Thesis"]},{"title":"Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo ","article_processing_charge":"No","publist_id":"8047","author":[{"last_name":"Belyaeva","full_name":"Belyaeva, Vera","first_name":"Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"short":"V. Belyaeva, Transcriptional Regulation of Macrophage Migration in the Drosophila Melanogaster Embryo , Institute of Science and Technology Austria, 2018.","ieee":"V. Belyaeva, “Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo ,” Institute of Science and Technology Austria, 2018.","apa":"Belyaeva, V. (2018). Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1064","ama":"Belyaeva V. Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo . 2018. doi:10.15479/AT:ISTA:th1064","mla":"Belyaeva, Vera. Transcriptional Regulation of Macrophage Migration in the Drosophila Melanogaster Embryo . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1064.","ista":"Belyaeva V. 2018. Transcriptional regulation of macrophage migration in the Drosophila melanogaster embryo . Institute of Science and Technology Austria.","chicago":"Belyaeva, Vera. “Transcriptional Regulation of Macrophage Migration in the Drosophila Melanogaster Embryo .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1064."},"oa":1,"publisher":"Institute of Science and Technology Austria","date_created":"2018-12-11T11:44:08Z","date_published":"2018-07-01T00:00:00Z","doi":"10.15479/AT:ISTA:th1064","page":"96","day":"01","year":"2018","has_accepted_license":"1","pubrep_id":"1064","status":"public","type":"dissertation","_id":"9","file_date_updated":"2021-02-11T11:17:16Z","department":[{"_id":"DaSi"}],"ddc":["570"],"date_updated":"2023-09-07T12:43:10Z","supervisor":[{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","first_name":"Daria E","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","last_name":"Siekhaus"}],"month":"07","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"Immune cells migrating to the sites of infection navigate through diverse tissue architectures and switch their migratory mechanisms upon demand. However, little is known about systemic regulators that could allow the acquisition of these mechanisms. We performed a genetic screen in Drosophila melanogaster to identify regulators of germband invasion by embryonic macrophages into the confined space between the ectoderm and mesoderm. We have found that bZIP circadian transcription factors (TFs) Kayak (dFos) and Vrille (dNFIL3) have opposite effects on macrophage germband infiltration: Kayak facilitated and Vrille inhibited it. These TFs are enriched in the macrophages during migration and genetically interact to control it. Kayak sets a less coordinated mode of migration of the macrophage group and increases the probability and length of Levy walks. Intriguingly, the motility of kayak mutant macrophages was also strongly affected during initial germband invasion but not along another less confined route. Inhibiting Rho1 signaling within the tail ectoderm partially rescued the Kayak mutant phenotype, strongly suggesting that migrating macrophages have to overcome a barrier imposed by the stiffness of the ectoderm. Also, Kayak appeared to be important for the maintenance of the round cell shape and the rear edge translocation of the macrophages invading the germband. Complementary to this, the cortical actin cytoskeleton of Kayak- deficient macrophages was strongly affected. RNA sequencing revealed the filamin Cheerio and tetraspanin TM4SF to be downstream of Kayak. Chromatin immunoprecipitation and immunostaining revealed that the formin Diaphanous is another downstream target of Kayak. Immunostaining revealed that the formin Diaphanous is another downstream target of Kayak. Indeed, Cheerio, TM4SF and Diaphanous are required within macrophages for germband invasion, and expression of constitutively active Diaphanous in macrophages was able to rescue the kayak mutant phenotype. Moreover, Cher and Diaphanous are also reduced in the macrophages overexpressing Vrille. We hypothesize that Kayak, through its targets, increases actin polymerization and cortical tension in macrophages and thus allows extra force generation necessary for macrophage dissemination and migration through confined stiff tissues, while Vrille counterbalances it.","lang":"eng"}],"language":[{"iso":"eng"}],"file":[{"file_name":"2018_Thesis_Belyaeva_source.docx","date_created":"2019-04-08T14:13:12Z","creator":"dernst","file_size":102737483,"date_updated":"2020-07-14T12:48:14Z","file_id":"6243","checksum":"d27b2465cb70d0c9678a0381b9b6ced1","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"},{"creator":"dernst","date_updated":"2021-02-11T11:17:16Z","file_size":88077843,"date_created":"2019-04-08T14:14:08Z","file_name":"2018_Thesis_Belyaeva.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"a2939b61bde2de7b8ced77bbae0eaaed","file_id":"6244","embargo":"2019-11-19"}],"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]}},{"title":"Design and characterization of methods and biological components to realize synthetic neurotransmission ","author":[{"id":"3EEDE19A-F248-11E8-B48F-1D18A9856A87","first_name":"Catherine","last_name":"Mckenzie","full_name":"Mckenzie, Catherine"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Mckenzie C. Design and characterization of methods and biological components to realize synthetic neurotransmission . 2018. doi:10.15479/at:ista:th_1055","apa":"Mckenzie, C. (2018). Design and characterization of methods and biological components to realize synthetic neurotransmission . Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:th_1055","ieee":"C. Mckenzie, “Design and characterization of methods and biological components to realize synthetic neurotransmission ,” Institute of Science and Technology Austria, 2018.","short":"C. Mckenzie, Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission , Institute of Science and Technology Austria, 2018.","mla":"Mckenzie, Catherine. Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission . Institute of Science and Technology Austria, 2018, doi:10.15479/at:ista:th_1055.","ista":"Mckenzie C. 2018. Design and characterization of methods and biological components to realize synthetic neurotransmission . Institute of Science and Technology Austria.","chicago":"Mckenzie, Catherine. “Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/at:ista:th_1055."},"date_published":"2018-10-31T00:00:00Z","doi":"10.15479/at:ista:th_1055","date_created":"2019-04-09T14:13:39Z","page":"95","day":"31","has_accepted_license":"1","year":"2018","publisher":"Institute of Science and Technology Austria","oa":1,"department":[{"_id":"HaJa"}],"file_date_updated":"2021-02-11T11:17:16Z","ddc":["571","573"],"supervisor":[{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L"}],"date_updated":"2023-09-07T13:02:37Z","status":"public","pubrep_id":"1055","type":"dissertation","_id":"6266","related_material":{"record":[{"relation":"new_edition","status":"public","id":"7132"}]},"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"6267","checksum":"9d2c2dca04b00e485470c28b262af59a","embargo":"2019-11-24","date_updated":"2021-02-11T11:17:16Z","file_size":4906420,"creator":"dernst","date_created":"2019-04-09T14:12:40Z","file_name":"2018_Thesis_McKenzie.pdf"},{"file_size":5053545,"date_updated":"2020-07-14T12:47:25Z","creator":"dernst","file_name":"2018_Thesis_McKenzie_source.docx","date_created":"2019-04-09T14:12:40Z","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","checksum":"50b58c272899601bc6fd9642c4dc97f1","file_id":"6268"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","month":"10","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta. Synthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing. "}]},{"date_published":"2018-06-22T00:00:00Z","doi":"10.15479/AT:ISTA:TH_1031","date_created":"2018-12-11T11:44:21Z","page":"95","day":"22","has_accepted_license":"1","year":"2018","publisher":"Institute of Science and Technology Austria","oa":1,"title":"Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration","publist_id":"8004","author":[{"last_name":"Capek","full_name":"Capek, Daniel","orcid":"0000-0001-5199-9940","id":"31C42484-F248-11E8-B48F-1D18A9856A87","first_name":"Daniel"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Capek, Daniel. “Optogenetic Frizzled 7 Reveals a Permissive Function of Wnt/PCP Signaling in Directed Mesenchymal Cell Migration.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:TH_1031.","ista":"Capek D. 2018. Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration. Institute of Science and Technology Austria.","mla":"Capek, Daniel. Optogenetic Frizzled 7 Reveals a Permissive Function of Wnt/PCP Signaling in Directed Mesenchymal Cell Migration. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:TH_1031.","apa":"Capek, D. (2018). Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:TH_1031","ama":"Capek D. Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration. 2018. doi:10.15479/AT:ISTA:TH_1031","ieee":"D. Capek, “Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration,” Institute of Science and Technology Austria, 2018.","short":"D. Capek, Optogenetic Frizzled 7 Reveals a Permissive Function of Wnt/PCP Signaling in Directed Mesenchymal Cell Migration, Institute of Science and Technology Austria, 2018."},"related_material":{"record":[{"relation":"part_of_dissertation","id":"1100","status":"public"},{"relation":"part_of_dissertation","id":"661","status":"public"},{"id":"676","status":"public","relation":"part_of_dissertation"}]},"file":[{"checksum":"d3eca3dcacb67bffdde6e6609c31cdd0","file_id":"6238","embargo":"2019-06-25","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2019-04-08T13:42:26Z","file_name":"2018_Thesis_Capek.pdf","date_updated":"2021-02-11T11:17:17Z","file_size":31576521,"creator":"dernst"},{"relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"6239","checksum":"876deb14067e638aba65d209668bd821","creator":"dernst","file_size":38992956,"date_updated":"2021-02-11T23:30:21Z","file_name":"2018_Thesis_Capek_source.docx","date_created":"2019-04-08T13:42:27Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","month":"06","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"The Wnt/planar cell polarity (Wnt/PCP) pathway determines planar polarity of epithelial cells in both vertebrates and invertebrates. The role that Wnt/PCP signaling plays in mesenchymal contexts, however, is only poorly understood. While previous studies have demonstrated the capacity of Wnt/PCP signaling to polarize and guide directed migration of mesenchymal cells, it remains unclear whether endogenous Wnt/PCP signaling performs these functions instructively, as it does in epithelial cells. Here we developed a light-switchable version of the Wnt/PCP receptor Frizzled 7 (Fz7) to unambiguously distinguish between an instructive and a permissive role of Wnt/PCP signaling for the directional collective migration of mesendoderm progenitor cells during zebrafish gastrulation. We show that prechordal plate (ppl) cell migration is defective in maternal-zygotic fz7a and fz7b (MZ fz7a,b) double mutant embryos, and that Fz7 functions cell-autonomously in this process by promoting ppl cell protrusion formation and directed migration. We further show that local activation of Fz7 can direct ppl cell migration both in vitro and in vivo. Surprisingly, however, uniform Fz7 activation is sufficient to fully rescue the ppl cell migration defect in MZ fz7a,b mutant embryos, indicating that Wnt/PCP signaling functions permissively rather than instructively in directed mesendoderm cell migration during zebrafish gastrulation."}],"file_date_updated":"2021-02-11T23:30:21Z","department":[{"_id":"CaHe"}],"ddc":["570","591","596"],"supervisor":[{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg"}],"date_updated":"2023-09-07T12:48:16Z","status":"public","pubrep_id":"1031","type":"dissertation","_id":"50"},{"date_published":"2018-10-30T00:00:00Z","doi":"10.15479/AT:ISTA:th1059","date_created":"2018-12-11T11:44:14Z","page":"109","day":"30","has_accepted_license":"1","year":"2018","publisher":"Institute of Science and Technology Austria","oa":1,"title":"The influence of sequence context on the evolution of bacterial gene expression","author":[{"orcid":"0000-0003-1229-9719","full_name":"Steinrück, Magdalena","last_name":"Steinrück","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","first_name":"Magdalena"}],"publist_id":"8029","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"apa":"Steinrück, M. (2018). The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1059","ama":"Steinrück M. The influence of sequence context on the evolution of bacterial gene expression. 2018. doi:10.15479/AT:ISTA:th1059","short":"M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018.","ieee":"M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018.","mla":"Steinrück, Magdalena. The Influence of Sequence Context on the Evolution of Bacterial Gene Expression. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1059.","ista":"Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria.","chicago":"Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1059."},"related_material":{"record":[{"relation":"part_of_dissertation","id":"704","status":"public"}]},"file":[{"creator":"dernst","file_size":9190845,"date_updated":"2020-07-14T12:45:43Z","file_name":"Thesis_Steinrueck_final.docx","date_created":"2019-02-08T10:51:22Z","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"5941","checksum":"413cbce1cd1debeae3abe2a25dbc70d1"},{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"3def8b7854c8b42d643597ce0215efac","file_id":"5942","embargo":"2019-11-02","date_updated":"2021-02-11T11:17:14Z","file_size":7521973,"creator":"dernst","date_created":"2019-02-08T10:51:22Z","file_name":"Thesis_Steinrueck_final.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","month":"10","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer.","lang":"eng"}],"department":[{"_id":"CaGu"}],"file_date_updated":"2021-02-11T11:17:14Z","ddc":["576","579"],"supervisor":[{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"}],"date_updated":"2023-09-07T12:48:43Z","status":"public","pubrep_id":"1059","type":"dissertation","_id":"26"},{"day":"01","publication":"Review of Scientific Instruments","isi":1,"year":"2018","doi":"10.1063/1.5038258","date_published":"2018-11-01T00:00:00Z","date_created":"2019-01-10T14:22:23Z","quality_controlled":"1","publisher":"AIP Publishing","oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"short":"A. Hollmann, D. Jirovec, M. Kucharski, D. Kissinger, G. Fischer, L.R. Schreiber, Review of Scientific Instruments 89 (2018).","ieee":"A. Hollmann, D. Jirovec, M. Kucharski, D. Kissinger, G. Fischer, and L. R. Schreiber, “30 GHz-voltage controlled oscillator operating at 4 K,” Review of Scientific Instruments, vol. 89, no. 11. AIP Publishing, 2018.","ama":"Hollmann A, Jirovec D, Kucharski M, Kissinger D, Fischer G, Schreiber LR. 30 GHz-voltage controlled oscillator operating at 4 K. Review of Scientific Instruments. 2018;89(11). doi:10.1063/1.5038258","apa":"Hollmann, A., Jirovec, D., Kucharski, M., Kissinger, D., Fischer, G., & Schreiber, L. R. (2018). 30 GHz-voltage controlled oscillator operating at 4 K. Review of Scientific Instruments. AIP Publishing. https://doi.org/10.1063/1.5038258","mla":"Hollmann, Arne, et al. “30 GHz-Voltage Controlled Oscillator Operating at 4 K.” Review of Scientific Instruments, vol. 89, no. 11, 114701, AIP Publishing, 2018, doi:10.1063/1.5038258.","ista":"Hollmann A, Jirovec D, Kucharski M, Kissinger D, Fischer G, Schreiber LR. 2018. 30 GHz-voltage controlled oscillator operating at 4 K. Review of Scientific Instruments. 89(11), 114701.","chicago":"Hollmann, Arne, Daniel Jirovec, Maciej Kucharski, Dietmar Kissinger, Gunter Fischer, and Lars R. Schreiber. “30 GHz-Voltage Controlled Oscillator Operating at 4 K.” Review of Scientific Instruments. AIP Publishing, 2018. https://doi.org/10.1063/1.5038258."},"title":"30 GHz-voltage controlled oscillator operating at 4 K","author":[{"first_name":"Arne","full_name":"Hollmann, Arne","last_name":"Hollmann"},{"last_name":"Jirovec","orcid":"0000-0002-7197-4801","full_name":"Jirovec, Daniel","id":"4C473F58-F248-11E8-B48F-1D18A9856A87","first_name":"Daniel"},{"first_name":"Maciej","last_name":"Kucharski","full_name":"Kucharski, Maciej"},{"first_name":"Dietmar","last_name":"Kissinger","full_name":"Kissinger, Dietmar"},{"full_name":"Fischer, Gunter","last_name":"Fischer","first_name":"Gunter"},{"first_name":"Lars R.","full_name":"Schreiber, Lars R.","last_name":"Schreiber"}],"external_id":{"arxiv":["1804.09522"],"isi":["000451735700054"]},"article_processing_charge":"No","article_number":"114701","language":[{"iso":"eng"}],"publication_identifier":{"issn":["00346748"]},"publication_status":"published","volume":89,"related_material":{"record":[{"status":"public","id":"10058","relation":"dissertation_contains"}]},"issue":"11","oa_version":"Preprint","abstract":[{"text":"Solid-state qubit manipulation and read-out fidelities are reaching fault-tolerance, but quantum error correction requires millions of physical qubits and therefore a scalable quantum computer architecture. To solve signal-line bandwidth and fan-out problems, microwave sources required for qubit manipulation might be embedded close to the qubit chip, typically operating at temperatures below 4 K. Here, we perform the first low temperature measurements of a 130 nm BiCMOS based SiGe voltage controlled oscillator at cryogenic temperature. We determined the frequency and output power dependence on temperature and magnetic field up to 5 T and measured the temperature influence on its noise performance. The device maintains its full functionality from 300 K to 4 K. The carrier frequency at 4 K increases by 3% with respect to the carrier frequency at 300 K, and the output power at 4 K increases by 10 dB relative to the output power at 300 K. The frequency tuning range of approximately 20% remains unchanged between 300 K and 4 K. In an in-plane magnetic field of 5 T, the carrier frequency shifts by only 0.02% compared to the frequency at zero magnetic field.","lang":"eng"}],"month":"11","intvolume":" 89","scopus_import":"1","main_file_link":[{"url":"https://arxiv.org/abs/1804.09522","open_access":"1"}],"date_updated":"2024-03-27T23:30:26Z","department":[{"_id":"GeKa"}],"_id":"5816","status":"public","type":"journal_article"},{"oa":1,"publisher":"Institute of Science and Technology Austria","year":"2018","has_accepted_license":"1","day":"28","page":"91","date_created":"2019-04-09T13:57:15Z","date_published":"2018-12-28T00:00:00Z","doi":"10.15479/AT:ISTA:th1072","citation":{"ama":"Lukacisinova M. Genetic determinants of antibiotic resistance evolution. 2018. doi:10.15479/AT:ISTA:th1072","apa":"Lukacisinova, M. (2018). Genetic determinants of antibiotic resistance evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1072","short":"M. Lukacisinova, Genetic Determinants of Antibiotic Resistance Evolution, Institute of Science and Technology Austria, 2018.","ieee":"M. Lukacisinova, “Genetic determinants of antibiotic resistance evolution,” Institute of Science and Technology Austria, 2018.","mla":"Lukacisinova, Marta. Genetic Determinants of Antibiotic Resistance Evolution. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1072.","ista":"Lukacisinova M. 2018. Genetic determinants of antibiotic resistance evolution. Institute of Science and Technology Austria.","chicago":"Lukacisinova, Marta. “Genetic Determinants of Antibiotic Resistance Evolution.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1072."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","author":[{"id":"4342E402-F248-11E8-B48F-1D18A9856A87","first_name":"Marta","last_name":"Lukacisinova","orcid":"0000-0002-2519-8004","full_name":"Lukacisinova, Marta"}],"title":"Genetic determinants of antibiotic resistance evolution","abstract":[{"text":"Antibiotic resistance can emerge spontaneously through genomic mutation and render treatment ineffective. To counteract this process, in addition to the discovery and description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand its determinantsis needed. To address this challenge, this thesisuncoversnew genetic determinants of resistance evolvability using a customized robotic setup, exploressystematic ways in which resistance evolution is perturbed due to dose-responsecharacteristics of drugs and mutation rate differences,and mathematically investigates the evolutionary fate of one specific type of evolvability modifier -a stress-induced mutagenesis allele.We find severalgenes which strongly inhibit or potentiate resistance evolution. In order to identify them, we first developedan automated high-throughput feedback-controlled protocol whichkeeps the population size and selection pressure approximately constant for hundreds of cultures by dynamically re-diluting the cultures and adjusting the antibiotic concentration. We implementedthis protocol on a customized liquid handling robot and propagated 100 different gene deletion strains of Escherichia coliin triplicate for over 100 generations in tetracycline and in chloramphenicol, and comparedtheir adaptation rates.We find a diminishing returns pattern, where initially sensitive strains adapted more compared to less sensitive ones. Our data uncover that deletions of certain genes which do not affect mutation rate,including efflux pump components, a chaperone and severalstructural and regulatory genes can strongly and reproducibly alterresistance evolution. Sequencing analysis of evolved populations indicates that epistasis with resistance mutations is the most likelyexplanation. This work could inspire treatment strategies in which targeted inhibitors of evolvability mechanisms will be given alongside antibiotics to slow down resistance evolution and extend theefficacy of antibiotics.We implemented astochasticpopulation genetics model, toverifyways in which general properties, namely, dose-response characteristics of drugs and mutation rates, influence evolutionary dynamics. In particular, under the exposure to antibiotics with shallow dose-response curves,bacteria have narrower distributions of fitness effects of new mutations. We show that in silicothis also leads to slower resistance evolution. We see and confirm with experiments that increased mutation rates, apart from speeding up evolution, also leadto high reproducibility of phenotypic adaptation in a context of continually strong selection pressure.Knowledge of these patterns can aid in predicting the dynamics of antibiotic resistance evolutionand adapting treatment schemes accordingly.Focusing on a previously described type of evolvability modifier –a stress-induced mutagenesis allele –we find conditions under which it can persist in a population under periodic selectionakin to clinical treatment. We set up a deterministic infinite populationcontinuous time model tracking the frequencies of a mutator and resistance allele and evaluate various treatment schemes in how well they maintain a stress-induced mutator allele. In particular,a high diversity of stresses is crucial for the persistence of the mutator allele. This leads to a general trade-off where exactly those diversifying treatment schemes which are likely to decrease levels of resistance could lead to stronger selection of highly evolvable genotypes.In the long run, this work will lead to a deeper understanding of the genetic and cellular mechanisms involved in antibiotic resistance evolution and could inspire new strategies for slowing down its rate. ","lang":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"LifeSc"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"12","degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"creator":"dernst","file_size":5656866,"date_updated":"2021-02-11T11:17:17Z","file_name":"2018_Thesis_Lukacisinova.pdf","date_created":"2019-04-09T13:49:24Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","embargo":"2020-01-25","checksum":"fc60585c9eaad868ac007004ef130908","file_id":"6264"},{"file_name":"2018_Thesis_Lukacisinova_source.docx","date_created":"2019-04-09T13:49:23Z","creator":"dernst","file_size":5168054,"date_updated":"2020-07-14T12:47:25Z","file_id":"6265","checksum":"264057ec0a92ab348cc83b41f021ba92","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"related_material":{"record":[{"status":"public","id":"1619","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"696","status":"public"},{"id":"1027","status":"public","relation":"part_of_dissertation"}]},"_id":"6263","type":"dissertation","status":"public","date_updated":"2023-09-22T09:20:37Z","supervisor":[{"first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach"}],"ddc":["570","576","579"],"department":[{"_id":"ToBo"}],"file_date_updated":"2021-02-11T11:17:17Z"},{"scopus_import":"1","month":"03","intvolume":" 8","acknowledged_ssus":[{"_id":"LifeSc"}],"abstract":[{"text":"Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult.","lang":"eng"}],"oa_version":"Published Version","volume":8,"related_material":{"record":[{"id":"6530","relation":"research_paper"},{"id":"6543","relation":"research_paper"},{"relation":"dissertation_contains","status":"public","id":"11193"},{"relation":"dissertation_contains","id":"6546","status":"public"}]},"issue":"3","ec_funded":1,"publication_status":"published","file":[{"file_size":2251222,"date_updated":"2020-07-14T12:46:56Z","creator":"system","file_name":"IST-2018-990-v1+1_2018_Gyoergy_Tools_allowing.pdf","date_created":"2018-12-12T10:11:48Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"7d9d28b915159078a4ca7add568010e8","file_id":"4905"}],"language":[{"iso":"eng"}],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"990","_id":"544","department":[{"_id":"DaSi"}],"file_date_updated":"2020-07-14T12:46:56Z","date_updated":"2024-03-27T23:30:29Z","ddc":["570"],"quality_controlled":"1","publisher":"Genetics Society of America","oa":1,"acknowledgement":" A. Ratheesh also by Marie Curie IIF GA-2012-32950BB:DICJI, Marko Roblek by the provincial government of Lower Austria, K. Valoskova and S. Wachner by DOC Fellowships from the Austrian Academy of Sciences, ","page":"845 - 857","doi":"10.1534/g3.117.300452","date_published":"2018-03-01T00:00:00Z","date_created":"2018-12-11T11:47:05Z","isi":1,"has_accepted_license":"1","year":"2018","day":"01","publication":"G3: Genes, Genomes, Genetics","project":[{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen"},{"call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"The role of Drosophila TNF alpha in immune cell invasion","grant_number":"P29638"},{"grant_number":"LSC16-021 ","name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis","_id":"2637E9C0-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077"}],"author":[{"first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","orcid":"0000-0002-1819-198X","full_name":"György, Attila"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","first_name":"Marko","full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","last_name":"Roblek"},{"orcid":"0000-0001-7190-0776","full_name":"Ratheesh, Aparna","last_name":"Ratheesh","first_name":"Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Valosková, Katarina","last_name":"Valosková","first_name":"Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Belyaeva","full_name":"Belyaeva, Vera","first_name":"Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","full_name":"Wachner, Stephanie","last_name":"Wachner"},{"full_name":"Matsubayashi, Yutaka","last_name":"Matsubayashi","first_name":"Yutaka"},{"full_name":"Sanchez Sanchez, Besaiz","last_name":"Sanchez Sanchez","first_name":"Besaiz"},{"first_name":"Brian","last_name":"Stramer","full_name":"Stramer, Brian"},{"first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353"}],"publist_id":"7271","article_processing_charge":"No","external_id":{"isi":["000426693300011"]},"title":"Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues","citation":{"ista":"György A, Roblek M, Ratheesh A, Valosková K, Belyaeva V, Wachner S, Matsubayashi Y, Sanchez Sanchez B, Stramer B, Siekhaus DE. 2018. Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. 8(3), 845–857.","chicago":"György, Attila, Marko Roblek, Aparna Ratheesh, Katarina Valosková, Vera Belyaeva, Stephanie Wachner, Yutaka Matsubayashi, Besaiz Sanchez Sanchez, Brian Stramer, and Daria E Siekhaus. “Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.” G3: Genes, Genomes, Genetics. Genetics Society of America, 2018. https://doi.org/10.1534/g3.117.300452.","ama":"György A, Roblek M, Ratheesh A, et al. Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. 2018;8(3):845-857. doi:10.1534/g3.117.300452","apa":"György, A., Roblek, M., Ratheesh, A., Valosková, K., Belyaeva, V., Wachner, S., … Siekhaus, D. E. (2018). Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. Genetics Society of America. https://doi.org/10.1534/g3.117.300452","ieee":"A. György et al., “Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues,” G3: Genes, Genomes, Genetics, vol. 8, no. 3. Genetics Society of America, pp. 845–857, 2018.","short":"A. György, M. Roblek, A. Ratheesh, K. Valosková, V. Belyaeva, S. Wachner, Y. Matsubayashi, B. Sanchez Sanchez, B. Stramer, D.E. Siekhaus, G3: Genes, Genomes, Genetics 8 (2018) 845–857.","mla":"György, Attila, et al. “Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.” G3: Genes, Genomes, Genetics, vol. 8, no. 3, Genetics Society of America, 2018, pp. 845–57, doi:10.1534/g3.117.300452."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","pubrep_id":"1013","status":"public","_id":"612","department":[{"_id":"RySh"}],"file_date_updated":"2020-07-14T12:47:20Z","date_updated":"2024-03-27T23:30:30Z","ddc":["571"],"scopus_import":"1","intvolume":" 223","month":"04","abstract":[{"lang":"eng","text":"Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network."}],"oa_version":"Published Version","ec_funded":1,"volume":223,"issue":"3","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"9562"}]},"publication_status":"published","language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"a55b3103476ecb5f4f983d8801807e8b","file_id":"5157","creator":"system","date_updated":"2020-07-14T12:47:20Z","file_size":5542926,"date_created":"2018-12-12T10:15:36Z","file_name":"IST-2018-1013-v1+1_2018_Kleindienst_Differential.pdf"}],"project":[{"call_identifier":"H2020","_id":"25CBA828-B435-11E9-9278-68D0E5697425","name":"Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)","grant_number":"720270"},{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"article_processing_charge":"No","external_id":{"isi":["000428419500030"]},"author":[{"first_name":"Rafael","full_name":"Luján, Rafael","last_name":"Luján"},{"full_name":"Aguado, Carolina","last_name":"Aguado","first_name":"Carolina"},{"first_name":"Francisco","last_name":"Ciruela","full_name":"Ciruela, Francisco"},{"full_name":"Cózar, Javier","last_name":"Cózar","first_name":"Javier"},{"full_name":"Kleindienst, David","last_name":"Kleindienst","first_name":"David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"De La Ossa","full_name":"De La Ossa, Luis","first_name":"Luis"},{"full_name":"Bettler, Bernhard","last_name":"Bettler","first_name":"Bernhard"},{"last_name":"Wickman","full_name":"Wickman, Kevin","first_name":"Kevin"},{"last_name":"Watanabe","full_name":"Watanabe, Masahiko","first_name":"Masahiko"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"},{"first_name":"Yugo","full_name":"Fukazawa, Yugo","last_name":"Fukazawa"}],"publist_id":"7192","title":"Differential association of GABAB receptors with their effector ion channels in Purkinje cells","citation":{"chicago":"Luján, Rafael, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis De La Ossa, Bernhard Bettler, et al. “Differential Association of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain Structure and Function. Springer, 2018. https://doi.org/10.1007/s00429-017-1568-y.","ista":"Luján R, Aguado C, Ciruela F, Cózar J, Kleindienst D, De La Ossa L, Bettler B, Wickman K, Watanabe M, Shigemoto R, Fukazawa Y. 2018. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. 223(3), 1565–1587.","mla":"Luján, Rafael, et al. “Differential Association of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain Structure and Function, vol. 223, no. 3, Springer, 2018, pp. 1565–87, doi:10.1007/s00429-017-1568-y.","ieee":"R. Luján et al., “Differential association of GABAB receptors with their effector ion channels in Purkinje cells,” Brain Structure and Function, vol. 223, no. 3. Springer, pp. 1565–1587, 2018.","short":"R. Luján, C. Aguado, F. Ciruela, J. Cózar, D. Kleindienst, L. De La Ossa, B. Bettler, K. Wickman, M. Watanabe, R. Shigemoto, Y. Fukazawa, Brain Structure and Function 223 (2018) 1565–1587.","apa":"Luján, R., Aguado, C., Ciruela, F., Cózar, J., Kleindienst, D., De La Ossa, L., … Fukazawa, Y. (2018). Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. Springer. https://doi.org/10.1007/s00429-017-1568-y","ama":"Luján R, Aguado C, Ciruela F, et al. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. 2018;223(3):1565-1587. doi:10.1007/s00429-017-1568-y"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"publisher":"Springer","quality_controlled":"1","page":"1565 - 1587","date_created":"2018-12-11T11:47:29Z","date_published":"2018-04-01T00:00:00Z","doi":"10.1007/s00429-017-1568-y","year":"2018","has_accepted_license":"1","isi":1,"publication":"Brain Structure and Function","day":"01"},{"acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award), both to P.J..","quality_controlled":"1","publisher":"Nature Publishing Group","oa":1,"day":"02","publication":"Nature Communications","has_accepted_license":"1","isi":1,"year":"2018","doi":"10.1038/s41467-018-06899-3","date_published":"2018-11-02T00:00:00Z","date_created":"2018-12-11T11:44:12Z","article_number":"4605","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Espinoza Martinez, Claudia , José Guzmán, Xiaomin Zhang, and Peter M Jonas. “Parvalbumin+ Interneurons Obey Unique Connectivity Rules and Establish a Powerful Lateral-Inhibition Microcircuit in Dentate Gyrus.” Nature Communications. Nature Publishing Group, 2018. https://doi.org/10.1038/s41467-018-06899-3.","ista":"Espinoza Martinez C, Guzmán J, Zhang X, Jonas PM. 2018. Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. 9(1), 4605.","mla":"Espinoza Martinez, Claudia, et al. “Parvalbumin+ Interneurons Obey Unique Connectivity Rules and Establish a Powerful Lateral-Inhibition Microcircuit in Dentate Gyrus.” Nature Communications, vol. 9, no. 1, 4605, Nature Publishing Group, 2018, doi:10.1038/s41467-018-06899-3.","apa":"Espinoza Martinez, C., Guzmán, J., Zhang, X., & Jonas, P. M. (2018). Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-018-06899-3","ama":"Espinoza Martinez C, Guzmán J, Zhang X, Jonas PM. Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-06899-3","ieee":"C. Espinoza Martinez, J. Guzmán, X. Zhang, and P. M. Jonas, “Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus,” Nature Communications, vol. 9, no. 1. Nature Publishing Group, 2018.","short":"C. Espinoza Martinez, J. Guzmán, X. Zhang, P.M. Jonas, Nature Communications 9 (2018)."},"title":"Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus","publist_id":"8034","author":[{"first_name":"Claudia ","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4710-2082","full_name":"Espinoza Martinez, Claudia ","last_name":"Espinoza Martinez"},{"full_name":"Guzmán, José","orcid":"0000-0003-2209-5242","last_name":"Guzmán","id":"30CC5506-F248-11E8-B48F-1D18A9856A87","first_name":"José"},{"first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","last_name":"Zhang","full_name":"Zhang, Xiaomin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"external_id":{"isi":["000449069700009"]},"article_processing_charge":"No","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+ interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+ interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations"}],"month":"11","intvolume":" 9","scopus_import":"1","file":[{"checksum":"9fe2a63bd95a5067d896c087d07998f3","file_id":"5715","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2018_NatureComm_Espinoza.pdf","date_created":"2018-12-17T15:41:57Z","file_size":4651930,"date_updated":"2020-07-14T12:45:28Z","creator":"dernst"}],"language":[{"iso":"eng"}],"publication_status":"published","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6363"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/lateral-inhibition-keeps-similar-memories-apart/","description":"News on IST Homepage"}]},"volume":9,"issue":"1","ec_funded":1,"_id":"21","status":"public","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"date_updated":"2024-03-27T23:30:31Z","department":[{"_id":"PeJo"}],"file_date_updated":"2020-07-14T12:45:28Z"},{"volume":118,"related_material":{"record":[{"relation":"dissertation_contains","id":"8934","status":"public"}]},"ec_funded":1,"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"68a055b1aaa241cc38375083cf832a7d","file_id":"5696","date_updated":"2020-07-14T12:47:34Z","file_size":1078309,"creator":"dernst","date_created":"2018-12-17T12:08:00Z","file_name":"2018_CONCUR_Chatterjee.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"isbn":["978-3-95977-087-3"]},"publication_status":"published","month":"09","intvolume":" 118","scopus_import":"1","alternative_title":["LIPIcs"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Crypto-currencies are digital assets designed to work as a medium of exchange, e.g., Bitcoin, but they are susceptible to attacks (dishonest behavior of participants). A framework for the analysis of attacks in crypto-currencies requires (a) modeling of game-theoretic aspects to analyze incentives for deviation from honest behavior; (b) concurrent interactions between participants; and (c) analysis of long-term monetary gains. Traditional game-theoretic approaches for the analysis of security protocols consider either qualitative temporal properties such as safety and termination, or the very special class of one-shot (stateless) games. However, to analyze general attacks on protocols for crypto-currencies, both stateful analysis and quantitative objectives are necessary. In this work our main contributions are as follows: (a) we show how a class of concurrent mean-payo games, namely ergodic games, can model various attacks that arise naturally in crypto-currencies; (b) we present the first practical implementation of algorithms for ergodic games that scales to model realistic problems for crypto-currencies; and (c) we present experimental results showing that our framework can handle games with thousands of states and millions of transitions."}],"file_date_updated":"2020-07-14T12:47:34Z","department":[{"_id":"KrCh"}],"ddc":["000"],"date_updated":"2024-03-27T23:30:33Z","status":"public","type":"conference","conference":{"start_date":"2018-09-04","location":"Beijing, China","end_date":"2018-09-07","name":"CONCUR: Conference on Concurrency Theory"},"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)"},"_id":"66","date_published":"2018-09-01T00:00:00Z","doi":"10.4230/LIPIcs.CONCUR.2018.11","date_created":"2018-12-11T11:44:27Z","day":"01","has_accepted_license":"1","year":"2018","quality_controlled":"1","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","oa":1,"title":"Ergodic mean-payoff games for the analysis of attacks in crypto-currencies","author":[{"orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","last_name":"Chatterjee","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Amir","id":"391365CE-F248-11E8-B48F-1D18A9856A87","full_name":"Goharshady, Amir","orcid":"0000-0003-1702-6584","last_name":"Goharshady"},{"orcid":"0000-0003-4783-0389","full_name":"Ibsen-Jensen, Rasmus","last_name":"Ibsen-Jensen","first_name":"Rasmus","id":"3B699956-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Velner","full_name":"Velner, Yaron","first_name":"Yaron"}],"publist_id":"7988","article_processing_charge":"No","external_id":{"arxiv":["1806.03108"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"short":"K. Chatterjee, A.K. Goharshady, R. Ibsen-Jensen, Y. Velner, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2018.","ieee":"K. Chatterjee, A. K. Goharshady, R. Ibsen-Jensen, and Y. Velner, “Ergodic mean-payoff games for the analysis of attacks in crypto-currencies,” presented at the CONCUR: Conference on Concurrency Theory, Beijing, China, 2018, vol. 118.","ama":"Chatterjee K, Goharshady AK, Ibsen-Jensen R, Velner Y. Ergodic mean-payoff games for the analysis of attacks in crypto-currencies. In: Vol 118. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2018. doi:10.4230/LIPIcs.CONCUR.2018.11","apa":"Chatterjee, K., Goharshady, A. K., Ibsen-Jensen, R., & Velner, Y. (2018). Ergodic mean-payoff games for the analysis of attacks in crypto-currencies (Vol. 118). Presented at the CONCUR: Conference on Concurrency Theory, Beijing, China: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.CONCUR.2018.11","mla":"Chatterjee, Krishnendu, et al. Ergodic Mean-Payoff Games for the Analysis of Attacks in Crypto-Currencies. Vol. 118, 11, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2018, doi:10.4230/LIPIcs.CONCUR.2018.11.","ista":"Chatterjee K, Goharshady AK, Ibsen-Jensen R, Velner Y. 2018. Ergodic mean-payoff games for the analysis of attacks in crypto-currencies. CONCUR: Conference on Concurrency Theory, LIPIcs, vol. 118, 11.","chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Rasmus Ibsen-Jensen, and Yaron Velner. “Ergodic Mean-Payoff Games for the Analysis of Attacks in Crypto-Currencies,” Vol. 118. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2018. https://doi.org/10.4230/LIPIcs.CONCUR.2018.11."},"project":[{"name":"Efficient Algorithms for Computer Aided Verification","grant_number":"ICT15-003","_id":"25892FC0-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Graph Games: Theory and Applications","grant_number":"279307","call_identifier":"FP7","_id":"2581B60A-B435-11E9-9278-68D0E5697425"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Rigorous Systems Engineering","grant_number":"S 11407_N23"},{"_id":"266EEEC0-B435-11E9-9278-68D0E5697425","name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts"}],"article_number":"11"},{"language":[{"iso":"eng"}],"file":[{"file_size":1394993,"date_updated":"2020-07-14T12:46:00Z","creator":"dernst","file_name":"2018_ESOP_Chatterjee.pdf","date_created":"2018-12-17T15:45:49Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"9c8a8338c571903b599b6ca93abd2cce","file_id":"5716"}],"publication_status":"published","ec_funded":1,"volume":10801,"related_material":{"record":[{"id":"8934","status":"public","relation":"dissertation_contains"}]},"oa_version":"Published Version","abstract":[{"text":"Smart contracts are computer programs that are executed by a network of mutually distrusting agents, without the need of an external trusted authority. Smart contracts handle and transfer assets of considerable value (in the form of crypto-currency like Bitcoin). Hence, it is crucial that their implementation is bug-free. We identify the utility (or expected payoff) of interacting with such smart contracts as the basic and canonical quantitative property for such contracts. We present a framework for such quantitative analysis of smart contracts. Such a formal framework poses new and novel research challenges in programming languages, as it requires modeling of game-theoretic aspects to analyze incentives for deviation from honest behavior and modeling utilities which are not specified as standard temporal properties such as safety and termination. While game-theoretic incentives have been analyzed in the security community, their analysis has been restricted to the very special case of stateless games. However, to analyze smart contracts, stateful analysis is required as it must account for the different program states of the protocol. Our main contributions are as follows: we present (i)~a simplified programming language for smart contracts; (ii)~an automatic translation of the programs to state-based games; (iii)~an abstraction-refinement approach to solve such games; and (iv)~experimental results on real-world-inspired smart contracts.","lang":"eng"}],"intvolume":" 10801","month":"04","alternative_title":["LNCS"],"scopus_import":"1","ddc":["000"],"date_updated":"2024-03-27T23:30:33Z","department":[{"_id":"KrCh"}],"file_date_updated":"2020-07-14T12:46:00Z","_id":"311","status":"public","conference":{"name":"ESOP: European Symposium on Programming","start_date":"2018-04-16","location":"Thessaloniki, Greece","end_date":"2018-04-19"},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"conference","day":"01","year":"2018","has_accepted_license":"1","date_created":"2018-12-11T11:45:45Z","date_published":"2018-04-01T00:00:00Z","doi":"10.1007/978-3-319-89884-1_26","page":"739 - 767","acknowledgement":"The research was partially supported by Vienna Science and Technology Fund (WWTF) Project ICT15-003, Austrian Science Fund (FWF) NFN Grant No S11407-N23 (RiSE/SHiNE), and ERC Starting grant (279307: Graph Games).","oa":1,"publisher":"Springer","quality_controlled":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, and Yaron Velner. “Quantitative Analysis of Smart Contracts,” 10801:739–67. Springer, 2018. https://doi.org/10.1007/978-3-319-89884-1_26.","ista":"Chatterjee K, Goharshady AK, Velner Y. 2018. Quantitative analysis of smart contracts. ESOP: European Symposium on Programming, LNCS, vol. 10801, 739–767.","mla":"Chatterjee, Krishnendu, et al. Quantitative Analysis of Smart Contracts. Vol. 10801, Springer, 2018, pp. 739–67, doi:10.1007/978-3-319-89884-1_26.","short":"K. Chatterjee, A.K. Goharshady, Y. Velner, in:, Springer, 2018, pp. 739–767.","ieee":"K. Chatterjee, A. K. Goharshady, and Y. Velner, “Quantitative analysis of smart contracts,” presented at the ESOP: European Symposium on Programming, Thessaloniki, Greece, 2018, vol. 10801, pp. 739–767.","apa":"Chatterjee, K., Goharshady, A. K., & Velner, Y. (2018). Quantitative analysis of smart contracts (Vol. 10801, pp. 739–767). Presented at the ESOP: European Symposium on Programming, Thessaloniki, Greece: Springer. https://doi.org/10.1007/978-3-319-89884-1_26","ama":"Chatterjee K, Goharshady AK, Velner Y. Quantitative analysis of smart contracts. In: Vol 10801. Springer; 2018:739-767. doi:10.1007/978-3-319-89884-1_26"},"title":"Quantitative analysis of smart contracts","article_processing_charge":"No","author":[{"first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X","last_name":"Chatterjee"},{"id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir","last_name":"Goharshady","orcid":"0000-0003-1702-6584","full_name":"Goharshady, Amir"},{"first_name":"Yaron","last_name":"Velner","full_name":"Velner, Yaron"}],"publist_id":"7554","project":[{"grant_number":"ICT15-003","name":"Efficient Algorithms for Computer Aided Verification","_id":"25892FC0-B435-11E9-9278-68D0E5697425"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"S 11407_N23","name":"Rigorous Systems Engineering"},{"_id":"2581B60A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Quantitative Graph Games: Theory and Applications","grant_number":"279307"}]},{"_id":"6340","type":"conference","conference":{"name":"IEEE International Conference on Blockchain","end_date":"2018-08-03","location":"Halifax, Canada","start_date":"2018-07-30"},"tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"status":"public","date_updated":"2024-03-27T23:30:34Z","ddc":["000"],"department":[{"_id":"KrCh"}],"file_date_updated":"2020-07-14T12:47:27Z","abstract":[{"text":"We present a secure approach for maintaining andreporting credit history records on the Blockchain. Our ap-proach removes third-parties such as credit reporting agen-cies from the lending process and replaces them with smartcontracts. This allows customers to interact directly with thelenders or banks while ensuring the integrity, unmalleabilityand privacy of their credit data. Additionally, each customerhas full control over complete or selective disclosure of hercredit records, eliminating the risk of privacy violations or databreaches. Moreover, our approach provides strong guaranteesfor the lenders as well. A lender can check both correctness andcompleteness of the credit data disclosed to her. This is the firstapproach that can perform all credit reporting tasks withouta central authority or changing the financial mechanisms*.","lang":"eng"}],"oa_version":"Submitted Version","scopus_import":"1","month":"09","publication_identifier":{"isbn":["978-1-5386-7975-3 "]},"publication_status":"published","file":[{"file_id":"6341","checksum":"b25c9bb7cf6e7e6634e692d26d41ead8","access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2019-04-18T10:36:39Z","file_name":"blockchain2018.pdf","creator":"akafshda","date_updated":"2020-07-14T12:47:27Z","file_size":624338}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8934"}]},"ec_funded":1,"project":[{"grant_number":"ICT15-003","name":"Efficient Algorithms for Computer Aided Verification","_id":"25892FC0-B435-11E9-9278-68D0E5697425"},{"_id":"266EEEC0-B435-11E9-9278-68D0E5697425","name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts"},{"grant_number":"279307","name":"Quantitative Graph Games: Theory and Applications","_id":"2581B60A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Rigorous Systems Engineering","grant_number":"S 11407_N23"}],"citation":{"chicago":"Goharshady, Amir Kafshdar, Ali Behrouz, and Krishnendu Chatterjee. “Secure Credit Reporting on the Blockchain.” In Proceedings of the IEEE International Conference on Blockchain, 1343–48. IEEE, 2018. https://doi.org/10.1109/Cybermatics_2018.2018.00231.","ista":"Goharshady AK, Behrouz A, Chatterjee K. 2018. Secure Credit Reporting on the Blockchain. Proceedings of the IEEE International Conference on Blockchain. IEEE International Conference on Blockchain, 1343–1348.","mla":"Goharshady, Amir Kafshdar, et al. “Secure Credit Reporting on the Blockchain.” Proceedings of the IEEE International Conference on Blockchain, IEEE, 2018, pp. 1343–48, doi:10.1109/Cybermatics_2018.2018.00231.","short":"A.K. Goharshady, A. Behrouz, K. Chatterjee, in:, Proceedings of the IEEE International Conference on Blockchain, IEEE, 2018, pp. 1343–1348.","ieee":"A. K. Goharshady, A. Behrouz, and K. Chatterjee, “Secure Credit Reporting on the Blockchain,” in Proceedings of the IEEE International Conference on Blockchain, Halifax, Canada, 2018, pp. 1343–1348.","ama":"Goharshady AK, Behrouz A, Chatterjee K. Secure Credit Reporting on the Blockchain. In: Proceedings of the IEEE International Conference on Blockchain. IEEE; 2018:1343-1348. doi:10.1109/Cybermatics_2018.2018.00231","apa":"Goharshady, A. K., Behrouz, A., & Chatterjee, K. (2018). Secure Credit Reporting on the Blockchain. In Proceedings of the IEEE International Conference on Blockchain (pp. 1343–1348). Halifax, Canada: IEEE. https://doi.org/10.1109/Cybermatics_2018.2018.00231"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir Kafshdar","last_name":"Goharshady","orcid":"0000-0003-1702-6584","full_name":"Goharshady, Amir Kafshdar"},{"first_name":"Ali","full_name":"Behrouz, Ali","last_name":"Behrouz"},{"last_name":"Chatterjee","full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"arxiv":["1805.09104"],"isi":["000481634500196"]},"article_processing_charge":"No","title":"Secure Credit Reporting on the Blockchain","publisher":"IEEE","quality_controlled":"1","oa":1,"isi":1,"has_accepted_license":"1","year":"2018","day":"01","publication":"Proceedings of the IEEE International Conference on Blockchain","page":"1343-1348","date_published":"2018-09-01T00:00:00Z","doi":"10.1109/Cybermatics_2018.2018.00231","date_created":"2019-04-18T10:37:35Z"}]