[{"degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"day":"29","doi":"10.15479/at:ista:17465","_id":"17465","project":[{"name":"Prix Lopez-Loretta 2019 - Marco Mondelli","_id":"059876FA-7A3F-11EA-A408-12923DDC885E"},{"grant_number":"W1260-N35","name":"Vienna Graduate School on Computational Optimization","_id":"9B9290DE-BA93-11EA-9121-9846C619BF3A"}],"supervisor":[{"last_name":"Mondelli","first_name":"Marco","full_name":"Mondelli, Marco","orcid":"0000-0002-3242-7020","id":"27EB676C-8706-11E9-9510-7717E6697425"},{"last_name":"Alistarh","orcid":"0000-0003-3650-940X","id":"4A899BFC-F248-11E8-B48F-1D18A9856A87","full_name":"Alistarh, Dan-Adrian","first_name":"Dan-Adrian"}],"oa_version":"Published Version","type":"dissertation","month":"08","ddc":["519"],"department":[{"_id":"GradSch"},{"_id":"DaAl"},{"_id":"MaMo"}],"page":"232","article_processing_charge":"No","has_accepted_license":"1","author":[{"first_name":"Aleksandr","id":"F2B06EC2-C99E-11E9-89F0-752EE6697425","full_name":"Shevchenko, Aleksandr","last_name":"Shevchenko"}],"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"}],"year":"2024","date_published":"2024-08-29T00:00:00Z","status":"public","publication_status":"published","corr_author":"1","alternative_title":["ISTA Thesis"],"citation":{"short":"A. Shevchenko, High-Dimensional Limits in Artificial Neural Networks, Institute of Science and Technology Austria, 2024.","chicago":"Shevchenko, Alexander. “High-Dimensional Limits in Artificial Neural Networks.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17465\">https://doi.org/10.15479/at:ista:17465</a>.","ista":"Shevchenko A. 2024. High-dimensional limits in artificial neural networks. Institute of Science and Technology Austria.","ama":"Shevchenko A. High-dimensional limits in artificial neural networks. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17465\">10.15479/at:ista:17465</a>","apa":"Shevchenko, A. (2024). <i>High-dimensional limits in artificial neural networks</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17465\">https://doi.org/10.15479/at:ista:17465</a>","ieee":"A. Shevchenko, “High-dimensional limits in artificial neural networks,” Institute of Science and Technology Austria, 2024.","mla":"Shevchenko, Alexander. <i>High-Dimensional Limits in Artificial Neural Networks</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17465\">10.15479/at:ista:17465</a>."},"file_date_updated":"2024-10-05T22:30:05Z","date_created":"2024-08-28T15:14:25Z","title":"High-dimensional limits in artificial neural networks","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"11420"},{"id":"17469","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"14459"},{"status":"public","id":"9198","relation":"part_of_dissertation"}]},"date_updated":"2025-04-25T10:32:06Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa":1,"file":[{"creator":"ashevche","file_size":4468610,"file_name":"thesis_a2b.pdf","content_type":"application/pdf","relation":"main_file","checksum":"da6dd3166078934577f6af93d27000e2","embargo":"2024-10-04","access_level":"open_access","date_updated":"2024-10-05T22:30:05Z","file_id":"17482","date_created":"2024-09-02T09:23:32Z"},{"creator":"ashevche","file_name":"Thesis Alex - ISTA.zip","file_size":15930999,"relation":"source_file","content_type":"application/zip","embargo_to":"open_access","checksum":"76a39ef252239560923cdda4ce0a31a4","access_level":"closed","date_updated":"2024-10-05T22:30:05Z","file_id":"17483","date_created":"2024-09-02T09:23:46Z"}],"abstract":[{"lang":"eng","text":"In the modern age of machine learning, artificial neural networks have become an integral part\r\nof many practical systems. One of the key ingredients of the success of the deep learning\r\napproach is recent computational advances which allowed the training of models with billions\r\nof parameters on large-scale data. Such over-parameterized and data-hungry regimes pose a\r\nchallenge for the theoretical analysis of modern models since “classical” statistical wisdom\r\nis no longer applicable. In this view, it is paramount to extend or develop new machinery\r\nthat will allow tackling the neural network analysis under new challenging asymptotic regimes,\r\nwhich is the focus of this thesis.\r\nLarge neural network systems are usually optimized via “local” search algorithms, such\r\nas stochastic gradient descent (SGD). However, given the high-dimensional nature of the\r\nparameter space, it is a priori not clear why such a crude “local” approach works so remarkably\r\nwell in practice. We take a step towards demystifying this phenomenon by showing that\r\nthe landscape of the SGD training dynamics exhibits a few beneficial properties for the\r\noptimization. First, we show that along the SGD trajectory an over-parameterized network\r\nis dropout stable. The emergence of dropout stability allows to conclude that the minima\r\nfound by SGD are connected via a continuous path of small loss. This in turn means that\r\nthe high-dimensional landscape of the neural network optimization problem is provably not so\r\nunfavourable to gradient-based training, due to mode connectivity. Next, we show that SGD\r\nfor an over-parameterized network tends to find solutions that are functionally more “simple”.\r\nThis in turn means that the SGD minima are more robust, since a less complicated solution\r\nwill less likely overfit the data. More formally, for a prototypical example of a wide two-layer\r\nReLU network on a 1d regression task we show that the SGD algorithm is implicitly selective in\r\nits choice of an interpolating solution. Namely, at convergence the neural network implements\r\na piece-wise linear function with the number of linear regions depending only on the amount\r\nof training data. This is in contrast to a “smooth”-like behaviour which one would expect\r\ngiven such a severe over-parameterization of the model.\r\nDiverging from the generic supervised setting of classification and regression problems, we\r\nanalyze an auto-encoder model that is commonly used for representation learning and data\r\ncompression. Despite the wide applicability of the auto-encoding paradigm, the theoretical\r\nunderstanding of their behaviour is limited even in the simplistic shallow case. The related\r\nwork is restricted to extreme asymptotic regimes in which the auto-encoder is either severely\r\nover-parameterized or under-parameterized. In contrast, we provide a tight characterization\r\nfor the 1-bit compression of Gaussian signals in the challenging proportional regime, i.e., the\r\ninput dimension and the size of the compressed representation obey the same asymptotics.\r\nWe also show that gradient-based methods are able to find a globally optimal solution and\r\nthat the predictions made for Gaussian data extrapolate beyond - to the case of compression\r\nof natural images. Next, we relax the Gaussian assumption and study more structured input\r\nsources. We show that the shallow model is sometimes agnostic to the structure of the data\r\nvii\r\nwhich results in a Gaussian-like behaviour. We prove that making the decoding component\r\nslightly less shallow is already enough to escape the “curse” of Gaussian performance.\r\n"}],"OA_place":"repository","publisher":"Institute of Science and Technology Austria"},{"title":"Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth","related_material":{"record":[{"status":"public","id":"17465","relation":"dissertation_contains"}]},"publication":"Proceedings of the 41st International Conference on Machine Learning","date_created":"2024-08-29T11:47:57Z","acknowledgement":"Kevin Kogler, Alexander Shevchenko and Marco Mondelli are supported by the 2019 Lopez-Loreta Prize. Hamed\r\nHassani acknowledges the support by the NSF CIF award (1910056) and the NSF Institute for CORE Emerging Methods in Data Science (EnCORE).","main_file_link":[{"url":"https://proceedings.mlr.press/v235/kogler24a.html","open_access":"1"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2026-06-14T22:30:04Z","arxiv":1,"abstract":[{"text":"Autoencoders are a prominent model in many empirical branches of machine learning and lossy data compression. However, basic theoretical questions remain unanswered even in a shallow two-layer setting. In particular, to what degree does a shallow autoencoder capture the structure of the underlying data distribution? For the prototypical case of the 1-bit compression of sparse Gaussian data, we prove that gradient descent converges to a solution that completely disregards the sparse structure of the input. Namely, the performance of the algorithm is the same as if it was compressing a Gaussian source - with no sparsity. For general data distributions, we give evidence of a phase transition phenomenon in the shape of the gradient descent minimizer, as a function of the data sparsity: below the critical sparsity level, the minimizer is a rotation taken uniformly at random (just like in the compression of non-sparse data); above the critical sparsity, the minimizer is the identity (up to a permutation). Finally, by exploiting a connection with approximate message passing algorithms, we show how to improve upon Gaussian performance for the compression of sparse data: adding a denoising function to a shallow architecture already reduces the loss provably, and a suitable multi-layer decoder leads to a further improvement. We validate our findings on image datasets, such as CIFAR-10 and MNIST.","lang":"eng"}],"oa":1,"publisher":"ML Research Press","author":[{"last_name":"Kögler","full_name":"Kögler, Kevin","id":"94ec913c-dc85-11ea-9058-e5051ab2428b","first_name":"Kevin"},{"id":"F2B06EC2-C99E-11E9-89F0-752EE6697425","full_name":"Shevchenko, Aleksandr","first_name":"Aleksandr","last_name":"Shevchenko"},{"full_name":"Hassani, Hamed","first_name":"Hamed","last_name":"Hassani"},{"last_name":"Mondelli","first_name":"Marco","full_name":"Mondelli, Marco","orcid":"0000-0002-3242-7020","id":"27EB676C-8706-11E9-9510-7717E6697425"}],"intvolume":"       235","language":[{"iso":"eng"}],"external_id":{"arxiv":["2402.05013"]},"quality_controlled":"1","corr_author":"1","alternative_title":["PMLR"],"citation":{"mla":"Kögler, Kevin, et al. “Compression of Structured Data with Autoencoders: Provable Benefit of Nonlinearities and Depth.” <i>Proceedings of the 41st International Conference on Machine Learning</i>, vol. 235, ML Research Press, 2024, pp. 24964–5015.","ama":"Kögler K, Shevchenko A, Hassani H, Mondelli M. Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth. In: <i>Proceedings of the 41st International Conference on Machine Learning</i>. Vol 235. ML Research Press; 2024:24964-25015.","ieee":"K. Kögler, A. Shevchenko, H. Hassani, and M. Mondelli, “Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth,” in <i>Proceedings of the 41st International Conference on Machine Learning</i>, Vienna, Austria, 2024, vol. 235, pp. 24964–25015.","apa":"Kögler, K., Shevchenko, A., Hassani, H., &#38; Mondelli, M. (2024). Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth. In <i>Proceedings of the 41st International Conference on Machine Learning</i> (Vol. 235, pp. 24964–25015). Vienna, Austria: ML Research Press.","ista":"Kögler K, Shevchenko A, Hassani H, Mondelli M. 2024. Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth. Proceedings of the 41st International Conference on Machine Learning. ICML: International Conference on Machine Learning, PMLR, vol. 235, 24964–25015.","chicago":"Kögler, Kevin, Alexander Shevchenko, Hamed Hassani, and Marco Mondelli. “Compression of Structured Data with Autoencoders: Provable Benefit of Nonlinearities and Depth.” In <i>Proceedings of the 41st International Conference on Machine Learning</i>, 235:24964–15. ML Research Press, 2024.","short":"K. Kögler, A. Shevchenko, H. Hassani, M. Mondelli, in:, Proceedings of the 41st International Conference on Machine Learning, ML Research Press, 2024, pp. 24964–25015."},"year":"2024","date_published":"2024-07-01T00:00:00Z","publication_status":"published","status":"public","type":"conference","month":"07","oa_version":"Published Version","department":[{"_id":"DaAl"},{"_id":"MaMo"}],"page":"24964-25015","scopus_import":"1","article_processing_charge":"No","day":"01","conference":{"name":"ICML: International Conference on Machine Learning","end_date":"2024-07-27","location":"Vienna, Austria","start_date":"2024-07-21"},"project":[{"_id":"059876FA-7A3F-11EA-A408-12923DDC885E","name":"Prix Lopez-Loretta 2019 - Marco Mondelli"}],"_id":"17469","volume":235},{"has_accepted_license":"1","author":[{"first_name":"Réka K","full_name":"Kelemen, Réka K","id":"48D3F8DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8489-9281","last_name":"Kelemen"}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","language":[{"iso":"eng"}],"citation":{"short":"R.K. Kelemen, Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver, Institute of Science and Technology Austria, 2024.","chicago":"Kelemen, Réka K. “Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17119\">https://doi.org/10.15479/at:ista:17119</a>.","apa":"Kelemen, R. K. (2024). <i>Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17119\">https://doi.org/10.15479/at:ista:17119</a>","ama":"Kelemen RK. Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17119\">10.15479/at:ista:17119</a>","ieee":"R. K. Kelemen, “Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver,” Institute of Science and Technology Austria, 2024.","ista":"Kelemen RK. 2024. Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. Institute of Science and Technology Austria.","mla":"Kelemen, Réka K. <i>Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17119\">10.15479/at:ista:17119</a>."},"file_date_updated":"2025-01-10T23:30:10Z","corr_author":"1","alternative_title":["ISTA Thesis"],"date_published":"2024-06-20T00:00:00Z","year":"2024","status":"public","publication_status":"published","title":"Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver","keyword":["meiotic driver","neofunctionalization","single nucleus sequencing"],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"542"},{"status":"public","id":"10767","relation":"part_of_dissertation"}]},"date_created":"2024-06-07T16:14:13Z","date_updated":"2026-04-07T13:21:37Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file":[{"embargo_to":"open_access","checksum":"fab59146e3b3dc2e5d214576984a2a63","relation":"source_file","content_type":"application/zip","file_name":"thesis.zip","file_size":180557931,"creator":"rkelemen","file_id":"17121","date_created":"2024-06-07T16:09:17Z","access_level":"closed","date_updated":"2025-01-10T23:30:10Z"},{"embargo":"2025-01-10","access_level":"open_access","date_updated":"2025-01-10T23:30:10Z","file_id":"17213","date_created":"2024-07-10T08:00:20Z","creator":"rkelemen","file_size":19405484,"file_name":"thesis_to_archive.pdf","content_type":"application/pdf","relation":"main_file","checksum":"91cc4c25a792239e8a7688e8aec7c62a"}],"OA_place":"publisher","abstract":[{"text":"Genomes are shaped by natural selection at the level of the organism, as genomic variants that\r\nhave a beneficial effect on the viability or fecundity of their carriers are on average expected\r\nto be passed on to more offspring than less beneficial alleles. However, selection also favors\r\ngenomic variants that drive their own transmission to the next generation above the mendelian\r\nexpectation of 50 percent in heterozygotes, even if these self-promoting variants are less\r\nbeneficial to the organism than other variants at the same locus. Such variants, called meiotic\r\ndrivers, are found in diverse taxa, and often impose fitness costs on their host organisms. As\r\nmeiotic drivers often require multiple genes and sequences for transmission ratio distortion,\r\nthey are often found in regions of low recombination, such as inversions, which prevent their\r\nrecombination with the non-driving homologous regions. Reduced recombination rates are\r\nexpected to lead to the accumulation of deleterious mutations, which may affect hundreds\r\nof genes trapped in the inversions of meiotic drivers. Although the observed fitness costs of\r\nself-promoting haplotypes are thought to possibly reflect sequence degeneration, no study has\r\nsystematically investigated the level of degeneration on a meiotic driver. Further, the low\r\nrates of recombination between driving and non-driving haplotypes have limited the power of\r\ntraditional genetic studies in uncovering the gene content of meiotic drivers, and made the\r\nthe identification of the genes causing transmission ratio distortion difficult.\r\nAfter an introduction to meiotic drivers in Chapter 1, this thesis presents three studies that\r\nmake use of next generation sequencing data to characterize the sequence and expression\r\nevolution of genes on the t-haplotype, a large and ancient meiotic driver in house mice that is\r\ntransmitted to up to 100% of the offspring in males heterozygous for it. Chapter 2 presents\r\na comprehensive assessment of the t-haplotype’s sequence evolution, which shows signs of\r\nsequence degeneration counteracted by occasional recombination with the non-driving homolog\r\nover large parts of the meiotic driver, proposing an explanation for its long-term survival.\r\nChapter 3 investigates the sequence and expression evolution of genes on the t-haplotype,\r\nand finds widespread expression and copy number changes and signs of less efficient purifying\r\nselection compared to the genes on the non-driving homolog. Further, this chapter finds\r\ncandidates for involvment in drive: two positively selected genes on the t-haplotype, and\r\nthe discovery of a t-specific gene duplicate, which was gained from another chromosome,\r\nand which acquired novel sequence and testis-specific expression on the t-haplotype. Finally,\r\nChapter 4 provides unprecedented insights into the gene expression landscape in testes of\r\nt-carrier mice, using single nucleus sequencing. Cell-resolved RNA-sequencing allows the\r\ncomparison of expression in spermatids carrying or not carrying the t-haplotype as well as the\r\ntiming of t-haplotype-induced expression changes along spermatogenesis. This study shows\r\nthe timing of previously found drive-associated genes, and uncovers novel candidate genes and\r\nbiological processes that may underlie the complex biology of transmission ratio distortion of\r\nthe t-haplotype. Chapter 5 synthesizes the findings of the three studies, and discusses them in\r\nthe context of the current state of meiotic drive research.","lang":"eng"}],"oa":1,"publisher":"Institute of Science and Technology Austria","ec_funded":1,"degree_awarded":"PhD","tmp":{"short":"CC BY-NC-SA (4.0)","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"doi":"10.15479/at:ista:17119","day":"20","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-039-8"]},"project":[{"call_identifier":"H2020","_id":"250BDE62-B435-11E9-9278-68D0E5697425","name":"Prevalence and Influence of Sexual Antagonism on Genome Evolution","grant_number":"715257"},{"_id":"34ae1506-11ca-11ed-8bc3-c14f4c474396","grant_number":"F8810","name":"The highjacking of meiosis for asexual reproduction"}],"_id":"17119","supervisor":[{"first_name":"Beatriz","orcid":"0000-0002-4579-8306","full_name":"Vicoso, Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","last_name":"Vicoso"}],"type":"dissertation","month":"06","oa_version":"Published Version","department":[{"_id":"GradSch"},{"_id":"BeVi"}],"page":"105","ddc":["576"],"article_processing_charge":"No"},{"article_processing_charge":"No","page":"124","department":[{"_id":"GradSch"},{"_id":"CaBe"}],"ddc":["572"],"month":"10","type":"dissertation","oa_version":"Published Version","supervisor":[{"orcid":"0000-0003-0893-7036","full_name":"Bernecky, Carrie A","id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","first_name":"Carrie A","last_name":"Bernecky"}],"_id":"18477","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"doi":"10.15479/at:ista:18477","day":"29","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-045-9"]},"degree_awarded":"PhD","publisher":"Institute of Science and Technology Austria","abstract":[{"text":"ADAR1 is broadly expressed across various tissues and is vital in regulating pathways\r\nassociated with innate immune responses. ADAR1 marks double-stranded RNA as \"self\"\r\nthrough its A-to-I editing activity, effectively repressing autoimmunity and maintaining\r\nimmune tolerance. This editing process has been detected at millions of sites across the\r\nhuman genome. However, the mechanism underlying ADAR1's substrate selectivity\r\nproperties remains largely unclear, with much of the current knowledge derived from\r\ncomparisons to its more extensively studied homolog, ADAR2. By studying ADAR1 in complex\r\nwith its RNA substrates and applying a combination of biochemical techniques and structural\r\nstudies using CryoEM, we aim to gain a more comprehensive understanding of the substrate\r\nselectivity characteristics of ADAR1.\r\nIn this thesis, the purification protocol for ADAR1 was successfully optimized, resulting in the\r\nfirst report in the literature to achieve high protein purity and activity. This advancement\r\nenabled the investigation of complex formation between ADAR1 and various RNA substrates,\r\nleading to the identification of optimal conditions for preparing the cryoEM sample. However,\r\ndespite comprehensive optimization of the cryo-EM conditions, the resulting data lacked the\r\ndesired quality, highlighting the need for similar rigorous optimization of the RNA substrates\r\nto facilitate structural studies of the ADAR1-RNA complex. The study was complemented by\r\nAlphaFold predictions, which provided some insights into this mechanism.\r\nMoreover, during this project I established a collaboration with a research group focused on\r\nstudying ADAR homologs. Notably ADAR homologs were identified in bivalve species, and it\r\nwas further demonstrated that ADAR and its A-to-I editing activity are upregulated in Pacific\r\noysters during infections with Ostreid herpesvirus-1—a highly infectious virus that leads to\r\nsignificant losses in oyster populations globally. I successfully purified oyster ADAR and\r\nprepared in vitro edited RNA for nanopore sequencing—a direct sequencing technology\r\ncapable of detecting modified nucleotides without the need for reverse transcription. The\r\ncollaborators initiated optimization of this nanopore-based approach. However, current\r\ntechnological limitations still constrain the reliable detection of modified nucleotides.\r\nThe project also examined the impact of RNA editing on RNA binding and filament formation\r\nby MDA5, a key cytosolic dsRNA sensor that triggers an interferon response. A primary target\r\nof ADAR1's editing activity is RNA derived from repetitive elements present in the genome,\r\nparticularly Alu elements forming double-stranded RNA. When unedited, these RNA\r\nsequences are recognized by MDA5. However, the mechanisms by which MDA5 interacts with\r\nAlu RNAs, as well as the role of A-to-I editing in influencing this binding, are still not well\r\nunderstood.\r\nThe interaction between MDA5 and Alu elements, was successfully established. This was\r\nachieved through the testing of different RNA variants and the evaluation of filament\r\nformation using binding techniques and electron microscopy imaging. This groundwork has\r\nset the conditions for further evaluation using CryoEM. Furthermore, the effects of A-to-I\r\nediting on the binding properties of MDA5 with Alu RNA were investigated. Given the recent\r\nresearch that has provided new insights into MDA5's interaction with dsRNA, it is essential to\r\nrevise the experimental setup to integrate these findings before moving forward with the\r\nCryoEM sample analysis.","lang":"eng"}],"file":[{"date_created":"2024-10-29T11:56:36Z","file_id":"18485","date_updated":"2025-10-29T23:30:02Z","access_level":"closed","checksum":"2053294ea4d770c495e4cc501e2a218b","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","file_size":23136626,"file_name":"20241029_PhD_thesis_BKaczmarek.docx","creator":"bkaczmar"},{"embargo":"2025-10-29","access_level":"open_access","date_updated":"2025-10-29T23:30:02Z","file_id":"18486","date_created":"2024-10-29T11:56:44Z","creator":"bkaczmar","file_name":"20241029_PhD_thesis_BKaczmarek.pdf","file_size":11707360,"relation":"main_file","content_type":"application/pdf","checksum":"8ce857a4cd44b776791eaf180ac9dbb3"}],"OA_place":"publisher","oa":1,"date_updated":"2026-04-07T13:23:59Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","title":"Biochemical and structural insights into ADAR1 RNA editing","date_created":"2024-10-27T07:35:13Z","corr_author":"1","citation":{"chicago":"Kaczmarek, Beata M. “Biochemical and Structural Insights into ADAR1 RNA Editing.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18477\">https://doi.org/10.15479/at:ista:18477</a>.","short":"B.M. Kaczmarek, Biochemical and Structural Insights into ADAR1 RNA Editing, Institute of Science and Technology Austria, 2024.","mla":"Kaczmarek, Beata M. <i>Biochemical and Structural Insights into ADAR1 RNA Editing</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18477\">10.15479/at:ista:18477</a>.","ista":"Kaczmarek BM. 2024. Biochemical and structural insights into ADAR1 RNA editing. Institute of Science and Technology Austria.","ieee":"B. M. Kaczmarek, “Biochemical and structural insights into ADAR1 RNA editing,” Institute of Science and Technology Austria, 2024.","ama":"Kaczmarek BM. Biochemical and structural insights into ADAR1 RNA editing. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18477\">10.15479/at:ista:18477</a>","apa":"Kaczmarek, B. M. (2024). <i>Biochemical and structural insights into ADAR1 RNA editing</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18477\">https://doi.org/10.15479/at:ista:18477</a>"},"file_date_updated":"2025-10-29T23:30:02Z","alternative_title":["ISTA Thesis"],"status":"public","publication_status":"published","year":"2024","date_published":"2024-10-29T00:00:00Z","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"author":[{"full_name":"Kaczmarek, Beata M","id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","first_name":"Beata M","last_name":"Kaczmarek"}],"has_accepted_license":"1"},{"doi":"10.15479/at:ista:17319","day":"26","publication_identifier":{"issn":["2663-337X"]},"supervisor":[{"last_name":"Sazanov","full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","first_name":"Leonid A"}],"_id":"17319","degree_awarded":"PhD","page":"224","department":[{"_id":"LeSa"},{"_id":"GradSch"}],"ddc":["580"],"article_processing_charge":"No","month":"07","type":"dissertation","oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"citation":{"mla":"Lukic, Kristina. <i>Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17319\">10.15479/at:ista:17319</a>.","ama":"Lukic K. Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17319\">10.15479/at:ista:17319</a>","apa":"Lukic, K. (2024). <i>Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17319\">https://doi.org/10.15479/at:ista:17319</a>","ieee":"K. Lukic, “Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B,” Institute of Science and Technology Austria, 2024.","ista":"Lukic K. 2024. Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. Institute of Science and Technology Austria.","chicago":"Lukic, Kristina. “Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17319\">https://doi.org/10.15479/at:ista:17319</a>.","short":"K. Lukic, Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B, Institute of Science and Technology Austria, 2024."},"corr_author":"1","file_date_updated":"2025-01-26T23:30:04Z","alternative_title":["ISTA Thesis"],"publication_status":"published","status":"public","date_published":"2024-07-26T00:00:00Z","year":"2024","has_accepted_license":"1","author":[{"last_name":"Lukic","first_name":"Kristina","full_name":"Lukic, Kristina","id":"2B04DB84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1581-881X"}],"file":[{"relation":"main_file","content_type":"application/pdf","checksum":"95517e697ea6a87e267e649cad560989","creator":"cchlebak","file_name":"Thesis_Kristina_Lukic.pdf","file_size":24639084,"date_created":"2024-07-26T13:14:24Z","file_id":"17320","embargo":"2025-01-26","date_updated":"2025-01-26T23:30:04Z","access_level":"open_access"},{"embargo_to":"open_access","checksum":"74325746a9a05078fb9935dbf2aef752","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","file_size":96334272,"file_name":"Thesis_Kristina_Lukic.docx","creator":"cchlebak","file_id":"17321","date_created":"2024-07-26T13:14:50Z","access_level":"closed","date_updated":"2025-01-26T23:30:04Z"}],"OA_place":"publisher","abstract":[{"lang":"eng","text":"This thesis comprises two distinct projects, each offering unique insights into fundamental\r\ncellular processes. While distinct in their focus, these different perspectives have a common\r\ntheme: chemiosmotic theory and utilisation of the proton gradient for driving the essential\r\nprocesses like auxin efflux and ATP synthesis, effectively bridging the membrane protein\r\nstructure and function from the realms of plant biology and cellular bioenergetics.\r\nThe first project of this thesis centres on the characterisation of PIN proteins, a class of\r\ntransmembrane transporters pivotal in the regulation of auxin transport and distribution in\r\nplants. PINs form a conserved and phylogenetically abundant group of transporters present in\r\nland plants and certain algae. Despite their great importance, they were one of the few elusive\r\nproteins essential for plant development not to be structurally and mechanistically\r\ncharacterised since their discovery almost 30 years ago. This work aimed to uncover the\r\nstructural and functional dynamics of the PIN protein-mediated auxin transport using an array\r\nof experimental techniques, including protein purification, biochemical assays and structural\r\nanalysis. Through an exhaustive screening process that took several years and included testing\r\ndifferent PIN homologues, expression systems, constructs, and purification conditions, we\r\ndeveloped a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein.\r\nMoreover, utilising biophysical methods and buffer screening, we demonstrated that PIN8\r\nexhibits detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and 6.0)\r\nbeing optimal for the stability of the protein. Using SEC-MALS and crosslinking, we\r\ndetermined that PIN8 forms dimers, which was confirmed by our structural studies. We\r\nobtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently published structures,\r\nour map implies major pH-dependent conformational changes and possibly utilisation of the\r\nproton gradient in the transport mechanism.\r\nThe subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental\r\nto cellular energy metabolism. Through an approach integrating biochemical assays and\r\nstructural analysis, this research aimed to unveil the molecular mechanism of inhibition of ATP\r\nsynthase by yaku´amide, a bioactive compound with potential therapeutic implications. Using\r\nsubmitochondrial particles and purified F1Fo-ATP synthase, we demonstrated that, contrary to\r\npublished data, yaku´amide inhibits both ATP hydrolysis and ATP synthesis reactions.\r\nMoreover, we found that yaku´amide inhibitory activity is proton motive force (pmf)\r\ndependent, with lower inhibition in a more coupled system. Utilising cryo-EM, we obtained\r\nmaps and models for the three main rotational states of murine ATP synthase (State 1 at 3.0 Å,\r\n8\r\nState 2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in our maps;\r\nhowever, we cannot definitively determine the exact mechanism of yaku amide’s inhibition on\r\nthe protein due to either resolution limits or suboptimal binding of the inhibitor."}],"oa":1,"publisher":"Institute of Science and Technology Austria","title":"Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku'amide B","date_created":"2024-07-26T09:05:55Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_updated":"2026-04-07T13:20:44Z"},{"page":"103","department":[{"_id":"GradSch"},{"_id":"JoCs"}],"ddc":["573"],"article_processing_charge":"No","month":"07","type":"dissertation","oa_version":"Published Version","day":"31","doi":"10.15479/at:ista:17346","publication_identifier":{"issn":["2663-337X"]},"supervisor":[{"first_name":"Jozsef L","full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari"}],"_id":"17346","degree_awarded":"PhD","file":[{"file_id":"17359","date_created":"2024-07-31T18:37:19Z","embargo":"2025-01-31","date_updated":"2025-01-31T23:30:03Z","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"12c76297cc27449da80c60d79127770d","creator":"lbollman","file_name":"PhD_Thesis_Lars_Bollmann.pdf","file_size":12920169},{"file_name":"Latex_source.zip","file_size":27568807,"creator":"lbollman","embargo_to":"open_access","checksum":"19a0265079dec8038830ad6e35c5106e","content_type":"application/zip","relation":"source_file","date_updated":"2025-01-31T23:30:03Z","access_level":"closed","date_created":"2024-07-31T18:38:39Z","file_id":"17360"}],"OA_place":"publisher","abstract":[{"lang":"eng","text":"Acquiring, retaining, and retrieving information over a wide range of timescales are crucial\r\nfunctions of the brain. The successful processing of memories affects many aspects of our\r\nlives and enables us and many other organisms to operate in a complex environment and\r\nto interact with it. In this context, the hippocampus and functionally connected brain\r\nareas, such as the prefrontal cortex, are central and have been subject to intensive research\r\nin the past decades. Storage of memories is believed to rely on distributed neural activity\r\nwithin these neural circuits. Additionally, neural memory traces of recent experience are\r\nreinstated during periods of rest or sleep. These reactivations are thought to play an\r\noutstanding role in the consolidation of memories and potentially facilitate the transfer of\r\ninformation from the hippocampus to cortical areas for long-term storage and integration\r\ninto existing knowledge.\r\nHowever, there is growing evidence that memory-related neural representations in the\r\nhippocampus are not as stable as initially thought and that they change even in the\r\nabsence of learning. It has been suggested that these changes reflect the accumulation of\r\nexperience, but the influence of interspersed consolidation periods has not been considered.\r\nPrevious studies have analyzed consolidation periods by detecting activity that strongly\r\nresembled neural activity during the acquisition of memory. Besides being often limited\r\nto only non-rapid eye movement (NREM) sleep, the used approaches were not capable of\r\ntracking changes in neural representations over extended temporal periods. More fluid\r\nrepresentations do not only challenge our understanding of how information is stored, but\r\nthey also affect the transfer of information between brain areas during the consolidation\r\nprocess.\r\nFor this thesis, I investigated the evolution of memory-related activity during sleep\r\nperiods expected to be involved in consolidation in the hippocampus and between the\r\nhippocampus and prefrontal cortex. I found that reactivated activity in the hippocampus\r\ngradually transformed during prolonged periods of sleep and inactivity. In the beginning,\r\nneural activity strongly resembled acquisition activity, whereas, with the progression of\r\ntime, it became more similar to the subsequent recall activity. NREM periods drove\r\nthis process, while rapid-eye movement (REM) periods showed a resetting effect. This\r\nreactivation drift was due to firing rate changes of a subset of cells and mirrored the\r\nrepresentational changes from the acquisition to the recall. A stable subset of cells\r\nwithstood the drift and maintained their activity. Therefore, my results indicate that\r\nmemory-related representations undergo spontaneous modifications during consolidation\r\nperiods and that these changes are predictive of representational drift.\r\nFurthermore, I found that the amount of change in the neural activity during subsequent\r\nsleep periods was biased by prior behavioral performance. Observed changes in the\r\nhippocampus and the prefrontal cortex were synchronized and increased after poor\r\nperformance, highlighting a potential role in the exchange of information. Low-variance\r\nvii\r\nperiods with distinct, more stable activity from a subset of cells significantly contributed\r\nto the heightened synchrony between both areas. Hence, interleaved phases of more stable\r\nneural activity could facilitate the information transfer between brain areas.\r\nIn conclusion, my investigations underline the fluidity of memory-related representations\r\nand assign a prominent role to sleep reactivation periods in their evolution. In addition, I\r\nidentified a potential mechanism of stable activity phases that might facilitate the synchronization across hippocampal-prefrontal activity despite ongoing changes. Reconciling\r\nand integrating findings from both spontaneous and behaviorally-related representational\r\nchanges in functionally related brain areas will help to broaden our understanding of how\r\nknowledge is stored, maintained, updated, and transferred between brain areas."}],"oa":1,"publisher":"Institute of Science and Technology Austria","keyword":["Memory","Hippocampus","Consolidation"],"title":"Stability and change in the memory system during rest","date_created":"2024-07-29T15:08:42Z","date_updated":"2026-04-07T13:21:20Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","language":[{"iso":"eng"}],"file_date_updated":"2025-01-31T23:30:03Z","corr_author":"1","citation":{"short":"L. Bollmann, Stability and Change in the Memory System during Rest, Institute of Science and Technology Austria, 2024.","chicago":"Bollmann, Lars. “Stability and Change in the Memory System during Rest.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17346\">https://doi.org/10.15479/at:ista:17346</a>.","ieee":"L. Bollmann, “Stability and change in the memory system during rest,” Institute of Science and Technology Austria, 2024.","ama":"Bollmann L. Stability and change in the memory system during rest. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17346\">10.15479/at:ista:17346</a>","apa":"Bollmann, L. (2024). <i>Stability and change in the memory system during rest</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17346\">https://doi.org/10.15479/at:ista:17346</a>","ista":"Bollmann L. 2024. Stability and change in the memory system during rest. Institute of Science and Technology Austria.","mla":"Bollmann, Lars. <i>Stability and Change in the Memory System during Rest</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17346\">10.15479/at:ista:17346</a>."},"alternative_title":["ISTA Thesis"],"status":"public","publication_status":"published","date_published":"2024-07-31T00:00:00Z","year":"2024","has_accepted_license":"1","author":[{"last_name":"Bollmann","first_name":"Lars","id":"47AD3038-F248-11E8-B48F-1D18A9856A87","full_name":"Bollmann, Lars"}]},{"publisher":"Institute of Science and Technology Austria","oa":1,"file":[{"content_type":"application/pdf","relation":"main_file","checksum":"095817a6c944954ac3f277e547031a33","creator":"cchlebak","file_size":5936142,"file_name":"Murmann_Thesis_final_2024_2.pdf","date_created":"2024-05-02T12:26:13Z","file_id":"15354","embargo":"2025-05-02","access_level":"open_access","date_updated":"2025-05-02T22:30:04Z"},{"checksum":"43b632255372973a437ac87739cfd4db","embargo_to":"open_access","content_type":"application/x-zip-compressed","relation":"source_file","file_size":20645510,"file_name":"Murmann_Thesis_final_2024.zip","creator":"cchlebak","date_created":"2024-05-02T12:37:56Z","file_id":"15355","access_level":"closed","date_updated":"2025-05-02T22:30:04Z"}],"abstract":[{"text":"Epilepsy affects about 50 to 65 million people globally. It summarizes a spectrum of neurological\r\ndisorders that have in common a hyperactivity of the neuronal network resulting in seizures. A common\r\nassumption is that an imbalance between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation and epileptogeneisis. In at least one-third of the patients, current therapies have\r\nproven unsuccessful in treating seizure progression. One potential reason could be that the therapies\r\nonly focus on neurons. Recent studies suggest that neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain homeostasis. Additionally, interactions between microglia and neurons\r\nhave been shown to inhibit neuronal firing and dampen seizure activity. However, the exact relationship\r\nbetween microglia and seizure progression in epilepsy is yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia dynamics due to their rapid response to environmental changes. On the other hand, in vivo\r\nstudies focus mostly on behavior characterization of the epileptic seizure phenotype and their long-term\r\nconsequences on microglia activity leaving out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere, we perform a pilot study to combine electroencephalography (EEG) and in vivo live imaging to\r\ndirectly monitor and correlate the onset of seizure activity with microglia response. To induce seizures,\r\nwe take advantage of the kainic acid (KA) model, which represents similar neuropathological and\r\nelectroencephalographic features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation of induction of the seizure and microglia activity in the hippocampus as a focal point, we\r\ninvestigated whether these changes also reached the primary visual cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that microglia changed their morphology at high doses\r\nof KA in the V1. Next, we optimized each of the two methodological components: for the EEG recording,\r\nour initial attempts under the microscope suffered from extensive electrical noise, which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia, we had to optimize the imaging parameters, so that we would be able to detect microglial\r\nprocesses in a sufficient resolution to track their process changes. Finally, we combined both\r\nmethodologies with the KA model. We confirmed that KA induced seizure activity and found first\r\nindication that those correlate with microglia volume changes.\r\nOverall, we have developed a first methodological approach, which allows the analysis of the acute\r\neffects of seizure onset on microglia. Future studies will have to continue to optimize the drift during\r\nimaging recording and the post-image analysis. ","lang":"eng"}],"OA_place":"publisher","date_updated":"2026-04-07T13:05:00Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2024-05-02T08:31:38Z","title":"Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording","year":"2024","date_published":"2024-05-02T00:00:00Z","publication_status":"published","status":"public","corr_author":"1","alternative_title":["ISTA Master's Thesis"],"citation":{"ama":"Murmann JS. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15352\">10.15479/at:ista:15352</a>","ieee":"J. S. Murmann, “Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and Technology Austria, 2024.","apa":"Murmann, J. S. (2024). <i>Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15352\">https://doi.org/10.15479/at:ista:15352</a>","ista":"Murmann JS. 2024. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria.","mla":"Murmann, Julie Stefanie. <i>Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15352\">10.15479/at:ista:15352</a>.","short":"J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and Technology Austria, 2024.","chicago":"Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15352\">https://doi.org/10.15479/at:ista:15352</a>."},"file_date_updated":"2025-05-02T22:30:04Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"author":[{"full_name":"Murmann, Julie Stefanie","id":"1d390868-f128-11eb-9611-a0ca5f7833b5","first_name":"Julie Stefanie","last_name":"Murmann"}],"has_accepted_license":"1","article_processing_charge":"No","ddc":["570"],"department":[{"_id":"SaSi"},{"_id":"GradSch"}],"page":"54","oa_version":"Published Version","type":"dissertation","month":"05","_id":"15352","supervisor":[{"full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","last_name":"Siegert"}],"publication_identifier":{"issn":["2791-4585"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"doi":"10.15479/at:ista:15352","day":"02","degree_awarded":"MS"},{"author":[{"first_name":"Heloisa","orcid":"0009-0004-2973-278X","full_name":"Chiossi, Heloisa","id":"2BBA502C-F248-11E8-B48F-1D18A9856A87","last_name":"Chiossi"}],"has_accepted_license":"1","file_date_updated":"2025-01-19T23:30:04Z","corr_author":"1","alternative_title":["ISTA Thesis"],"citation":{"chicago":"Chiossi, Heloisa S. C. “Adaptive Hierarchical Representations in the Hippocampus.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:14821\">https://doi.org/10.15479/at:ista:14821</a>.","short":"H.S.C. Chiossi, Adaptive Hierarchical Representations in the Hippocampus, Institute of Science and Technology Austria, 2024.","mla":"Chiossi, Heloisa S. C. <i>Adaptive Hierarchical Representations in the Hippocampus</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:14821\">10.15479/at:ista:14821</a>.","ama":"Chiossi HSC. Adaptive hierarchical representations in the hippocampus. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:14821\">10.15479/at:ista:14821</a>","ieee":"H. S. C. Chiossi, “Adaptive hierarchical representations in the hippocampus,” Institute of Science and Technology Austria, 2024.","apa":"Chiossi, H. S. C. (2024). <i>Adaptive hierarchical representations in the hippocampus</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:14821\">https://doi.org/10.15479/at:ista:14821</a>","ista":"Chiossi HSC. 2024. Adaptive hierarchical representations in the hippocampus. Institute of Science and Technology Austria."},"date_published":"2024-01-19T00:00:00Z","year":"2024","publication_status":"published","status":"public","language":[{"iso":"eng"}],"date_updated":"2026-04-07T13:21:56Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","title":"Adaptive hierarchical representations in the hippocampus","date_created":"2024-01-16T14:25:21Z","publisher":"Institute of Science and Technology Austria","ec_funded":1,"file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","embargo_to":"open_access","checksum":"d3fa3de1abd5af5204c13e9d55375615","creator":"hchiossi","file_name":"PhD_Thesis_190124.docx","file_size":8656268,"file_id":"14838","date_created":"2024-01-19T11:04:05Z","access_level":"closed","date_updated":"2025-01-19T23:30:04Z"},{"checksum":"13adc8dcfb5b6b18107f89f0a98fa8bd","content_type":"application/pdf","relation":"main_file","file_size":6567275,"file_name":"PhD_Thesis_190124.pdf","creator":"hchiossi","file_id":"14839","date_created":"2024-01-19T11:03:59Z","access_level":"open_access","date_updated":"2025-01-19T23:30:04Z","embargo":"2025-01-19"}],"OA_place":"publisher","abstract":[{"text":"The hippocampus is central to memory formation, storage and retrieval over many\r\ntimescales. Neurons in this brain area are highly selective to spatial position as well as to many\r\nother variables of the environment. It is believed that the selectivity patterns of hippocampal\r\nneurons reflect the structure of tasks an animal performs. However, especially at timescales\r\nlonger than a few minutes or hours it is not fully known how these representations evolve, nor\r\nhow they map to behaviour in the process. In this thesis, I monitored the evolution of\r\nhippocampal representations in a novel spatial-associative memory task for rats. Reward\r\nlocations were associated with global sensory cues (i.e. context); animals had to remember the\r\nassociations and dig for food in those locations only. I used in vivo electrophysiology to record\r\nthe activity of the hippocampus dorsal CA1 neurons during the learning period of a few days.\r\nI report here a novel and simple method to classify behaviour performance to account\r\nfor individual variability in learning speed and spurious performance unrelated to true task rule\r\nlearning. Using this classification I was then able to investigate neural responses on different\r\nstages of learning matched across animals. On the first day of learning, I observed a fast\r\nformation of single-cell selectivity to task variables which remained stable over days. I also\r\nobserved that reward tuning was not a single process but dependent on task-related cognitive\r\nload. At the population level, a linear decoding approach revealed a hierarchy in the\r\nrepresentation of task variables that changed with learning. In the high-dimensional space of\r\npopulation activity, the representation of contexts was specific to each position in the maze, and\r\ncould thus be better decoded if the position was known. The decoding of position did not improve\r\nwith knowledge of other variables. As learning progressed, the hippocampal code underwent a\r\nreorganisation of high-variance directions in population activity, identified by principal\r\ncomponent analysis. I found that dominant dimensions started carrying increasing amounts of\r\ninformation about task context specifically at those positions where it mattered for task\r\nperformance. When I contrasted this with variables less relevant to task performance (e.g.\r\nmovement direction), I did not observe differences in decoding quality over positions nor a\r\nreduction of dimensionality with learning.\r\nOverall, the largest changes in CA1 neural response with task learning happened in a\r\nmatter of a few trials; over days, changes undetectable in single-cell statistics were responsible\r\nfor re-structuring the hierarchy of neural representations at the population level; these changes\r\nwere task-specific and reflected different stages of learning. This indicates that complex task\r\nlearning may involve different magnitudes of response modulation in CA1, which happen at\r\nspecific time scales linked to behaviour.","lang":"eng"}],"oa":1,"degree_awarded":"PhD","_id":"14821","project":[{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"supervisor":[{"last_name":"Csicsvari","full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5193-4036","first_name":"Jozsef L"}],"day":"19","doi":"10.15479/at:ista:14821","publication_identifier":{"issn":["2663-337X"]},"type":"dissertation","month":"01","oa_version":"Published Version","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"JoCs"}],"page":"89","ddc":["570"]},{"corr_author":"1","citation":{"chicago":"Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-024-01255-0\">https://doi.org/10.1038/s41594-024-01255-0</a>.","short":"I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology 31 (2024) 1061–1071.","mla":"Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>, vol. 31, Springer Nature, 2024, pp. 1061–71, doi:<a href=\"https://doi.org/10.1038/s41594-024-01255-0\">10.1038/s41594-024-01255-0</a>.","ista":"Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of mammalian respirasomes. Nature Structural and Molecular Biology. 31, 1061–1071.","ama":"Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>. 2024;31:1061-1071. doi:<a href=\"https://doi.org/10.1038/s41594-024-01255-0\">10.1038/s41594-024-01255-0</a>","ieee":"I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity of mammalian respirasomes,” <i>Nature Structural and Molecular Biology</i>, vol. 31. Springer Nature, pp. 1061–1071, 2024.","apa":"Vercellino, I., &#38; Sazanov, L. A. (2024). SCAF1 drives the compositional diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-024-01255-0\">https://doi.org/10.1038/s41594-024-01255-0</a>"},"file_date_updated":"2025-01-01T23:30:03Z","date_published":"2024-07-01T00:00:00Z","year":"2024","publication_status":"published","status":"public","external_id":{"pmid":["38575788"],"isi":["001196897300001"]},"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"ScienComp"}],"quality_controlled":"1","author":[{"id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5618-3449","full_name":"Vercellino, Irene","first_name":"Irene","last_name":"Vercellino"},{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","first_name":"Leonid A"}],"intvolume":"        31","has_accepted_license":"1","publisher":"Springer Nature","ec_funded":1,"file":[{"creator":"lsazanov","file_size":24424729,"file_name":"megacomplex_submit_NSMB_withFigures.pdf","content_type":"application/pdf","relation":"main_file","checksum":"21f05d188762acd7f49a97f3d09c8d9f","embargo":"2025-01-01","access_level":"open_access","date_updated":"2025-01-01T23:30:03Z","file_id":"15392","date_created":"2024-05-14T11:57:56Z"}],"abstract":[{"lang":"eng","text":"Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions."}],"oa":1,"date_updated":"2025-11-24T08:35:04Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"title":"SCAF1 drives the compositional diversity of mammalian respirasomes","related_material":{"link":[{"url":"https://doi.org/10.1038/s41594-025-01721-3","relation":"erratum"}]},"publication":"Nature Structural and Molecular Biology","date_created":"2024-04-14T22:01:03Z","acknowledgement":"Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions.","_id":"15323","project":[{"grant_number":"101020697","name":"Structure and mechanism of respiratory chain molecular machines","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3","call_identifier":"H2020"}],"volume":31,"doi":"10.1038/s41594-024-01255-0","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"day":"01","publication_identifier":{"eissn":["1545-9985"],"issn":["1545-9993"]},"article_type":"original","article_processing_charge":"No","department":[{"_id":"LeSa"}],"page":"1061-1071","scopus_import":"1","isi":1,"ddc":["572"],"type":"journal_article","month":"07","oa_version":"Submitted Version"},{"DOAJ_listed":"1","oa_version":"Published Version","month":"12","type":"journal_article","article_processing_charge":"Yes","isi":1,"scopus_import":"1","page":"1-29","department":[{"_id":"GradSch"},{"_id":"JaMa"}],"article_type":"original","project":[{"_id":"fc31cba2-9c52-11eb-aca3-ff467d239cd2","name":"Taming Complexity in Partial Differential Systems","grant_number":"F6504"}],"_id":"18706","publication_identifier":{"issn":["0956-7925"],"eissn":["1469-4425"]},"day":"20","doi":"10.1017/s0956792524000810","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1017/S0956792524000810"}],"date_updated":"2026-06-14T22:30:19Z","acknowledgement":"L.P. gratefully acknowledges fundings from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – GZ 2047/1, Projekt-ID 390685813. F.Q. gratefully acknowledges support from the Austrian Science Fund (FWF) project 10.55776/F65.","date_created":"2024-12-23T11:03:59Z","publication":"European Journal of Applied Mathematics","related_material":{"record":[{"relation":"dissertation_contains","id":"20563","status":"public"}]},"title":"Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs","publisher":"Cambridge University Press","oa":1,"abstract":[{"lang":"eng","text":"We prove discrete-to-continuum convergence for dynamical optimal transport on  Zd\r\n -periodic graphs with cost functional having linear growth at infinity. This result provides an answer to a problem left open by Gladbach, Kopfer, Maas, and Portinale (Calc Var Partial Differential Equations 62(5), 2023), where the convergence behaviour of discrete boundary-value dynamical transport problems is proved under the stronger assumption of superlinear growth. Our result extends the known literature to some important classes of examples, such as scaling limits of  1 -Wasserstein transport problems. Similarly to what happens in the quadratic case, the geometry of the graph plays a crucial role in the structure of the limit cost function, as we discuss in the final part of this work, which includes some visual representations."}],"OA_place":"publisher","author":[{"last_name":"Portinale","first_name":"Lorenzo","full_name":"Portinale, Lorenzo","id":"30AD2CBC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Quattrocchi","orcid":"0009-0000-9773-1931","id":"3ebd6ba8-edfb-11eb-afb5-91a9745ba308","full_name":"Quattrocchi, Filippo","first_name":"Filippo"}],"publication_status":"epub_ahead","status":"public","year":"2024","date_published":"2024-12-20T00:00:00Z","citation":{"chicago":"Portinale, Lorenzo, and Filippo Quattrocchi. “Discrete-to-Continuum Limits of Optimal Transport with Linear Growth on Periodic Graphs.” <i>European Journal of Applied Mathematics</i>. Cambridge University Press, 2024. <a href=\"https://doi.org/10.1017/s0956792524000810\">https://doi.org/10.1017/s0956792524000810</a>.","short":"L. Portinale, F. Quattrocchi, European Journal of Applied Mathematics (2024) 1–29.","mla":"Portinale, Lorenzo, and Filippo Quattrocchi. “Discrete-to-Continuum Limits of Optimal Transport with Linear Growth on Periodic Graphs.” <i>European Journal of Applied Mathematics</i>, Cambridge University Press, 2024, pp. 1–29, doi:<a href=\"https://doi.org/10.1017/s0956792524000810\">10.1017/s0956792524000810</a>.","ieee":"L. Portinale and F. Quattrocchi, “Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs,” <i>European Journal of Applied Mathematics</i>. Cambridge University Press, pp. 1–29, 2024.","ama":"Portinale L, Quattrocchi F. Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs. <i>European Journal of Applied Mathematics</i>. 2024:1-29. doi:<a href=\"https://doi.org/10.1017/s0956792524000810\">10.1017/s0956792524000810</a>","apa":"Portinale, L., &#38; Quattrocchi, F. (2024). Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs. <i>European Journal of Applied Mathematics</i>. Cambridge University Press. <a href=\"https://doi.org/10.1017/s0956792524000810\">https://doi.org/10.1017/s0956792524000810</a>","ista":"Portinale L, Quattrocchi F. 2024. Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs. European Journal of Applied Mathematics., 1–29."},"OA_type":"gold","quality_controlled":"1","language":[{"iso":"eng"}],"external_id":{"isi":["001381435800001"]}},{"author":[{"full_name":"Quattrocchi, Filippo","orcid":"0009-0000-9773-1931","id":"3ebd6ba8-edfb-11eb-afb5-91a9745ba308","first_name":"Filippo","last_name":"Quattrocchi"}],"date_published":"2024-04-09T00:00:00Z","year":"2024","publication_status":"draft","status":"public","citation":{"mla":"Quattrocchi, Filippo. “Variational Structures for the Fokker-Planck Equation with General Dirichlet Boundary Conditions.” <i>ArXiv</i>, 2403.07803, doi:<a href=\"https://doi.org/10.48550/arXiv.2403.07803\">10.48550/arXiv.2403.07803</a>.","ista":"Quattrocchi F. Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions. arXiv, 2403.07803.","ama":"Quattrocchi F. Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2403.07803\">10.48550/arXiv.2403.07803</a>","ieee":"F. Quattrocchi, “Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions,” <i>arXiv</i>. .","apa":"Quattrocchi, F. (n.d.). Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2403.07803\">https://doi.org/10.48550/arXiv.2403.07803</a>","chicago":"Quattrocchi, Filippo. “Variational Structures for the Fokker-Planck Equation with General Dirichlet Boundary Conditions.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2403.07803\">https://doi.org/10.48550/arXiv.2403.07803</a>.","short":"F. Quattrocchi, ArXiv (n.d.)."},"OA_type":"green","corr_author":"1","external_id":{"arxiv":["2403.07803"]},"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","arxiv":1,"date_updated":"2026-06-14T22:30:19Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.48550/arXiv.2403.07803"}],"date_created":"2025-10-28T13:12:56Z","acknowledgement":"The author would like to thank Jan Maas for suggesting this project and for many helpful\r\ncomments, Antonio Agresti, Lorenzo Dello Schiavo and Julian Fischer for several fruitful discussions, and Oliver Tse for pointing out the reference [15]. He also gratefully acknowledges support from the Austrian Science Fund (FWF) project 10.55776/F65.\r\n","title":"Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions","keyword":["gradient flows","Jordan–Kinderlehrer–Otto scheme","curves of maximal slope","optimal transport","Dirichlet boundary conditions","Fokker–Planck equation"],"publication":"arXiv","related_material":{"record":[{"status":"public","id":"20865","relation":"later_version"},{"id":"20563","relation":"dissertation_contains","status":"public"}]},"oa":1,"OA_place":"repository","abstract":[{"text":"We prove the convergence of a modified Jordan--Kinderlehrer--Otto scheme to a solution to the Fokker--Planck equation in $\\Omega \\Subset \\mathbb{R}^d$ with general, positive and temporally constant, Dirichlet boundary conditions. We work under mild assumptions on the domain, the drift, and the initial datum.   In the special case where $\\Omega$ is an interval in $\\mathbb{R}^1$, we prove that such a solution is a gradient flow -- curve of maximal slope -- within a suitable space of measures, endowed with a modified Wasserstein distance.\r\nOur discrete scheme and modified distance draw inspiration from contributions by A. Figalli and N. Gigli [J. Math. Pures Appl. 94, (2010), pp. 107--130], and J. Morales [J. Math. Pures Appl. 112, (2018), pp. 41--88] on an optimal-transport approach to evolution equations with Dirichlet boundary conditions. Similarly to these works, we allow the mass to flow from/to the boundary $\\partial \\Omega$ throughout the evolution. However, our leading idea is to also keep track of the mass at the boundary by working with measures defined on the whole closure $\\overline \\Omega$. The driving functional is a modification of the classical relative entropy that also makes use of the information at the boundary. As an intermediate result, when $\\Omega$ is an interval in $\\mathbb{R}^1$, we find a formula for the descending slope of this geodesically nonconvex functional. ","lang":"eng"}],"article_number":"2403.07803","project":[{"call_identifier":"FWF","name":"Taming Complexity in Partial Differential Systems","grant_number":"F06504","_id":"260482E2-B435-11E9-9278-68D0E5697425"}],"_id":"20571","day":"09","doi":"10.48550/arXiv.2403.07803","oa_version":"Preprint","type":"preprint","month":"04","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"JaMa"}]},{"article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"JaMa"}],"oa_version":"Preprint","type":"preprint","month":"08","project":[{"call_identifier":"FWF","name":"Taming Complexity in Partial Differential Systems","grant_number":"F06504","_id":"260482E2-B435-11E9-9278-68D0E5697425"}],"_id":"20570","day":"23","doi":"10.48550/arXiv.2408.12924","article_number":"2408.12924","oa":1,"OA_place":"repository","abstract":[{"text":"We investigate the minimal error in approximating a general probability\r\nmeasure $\\mu$ on $\\mathbb{R}^d$ by the uniform measure on a finite set with\r\nprescribed cardinality $n$. The error is measured in the $p$-Wasserstein\r\ndistance. In particular, when $1\\le p<d$, we establish asymptotic upper and\r\nlower bounds as $n \\to \\infty$ on the rescaled minimal error that have the\r\nsame, explicit dependency on $\\mu$.\r\n  In some instances, we prove that the rescaled minimal error has a limit.\r\nThese include general measures in dimension $d = 2$ with $1 \\le p < 2$, and\r\nuniform measures in arbitrary dimension with $1 \\le p < d$. For some uniform\r\nmeasures, we prove the limit existence for $p \\ge d$ as well.\r\n  For a class of compactly supported measures with H\\\"older densities, we\r\ndetermine the convergence speed of the minimal error for every $p \\ge 1$.\r\n  Furthermore, we establish a new Pierce-type (i.e., nonasymptotic) upper\r\nestimate of the minimal error when $1 \\le p < d$.\r\n  In the initial sections, we survey the state of the art and draw connections\r\nwith similar problems, such as classical and random quantization.","lang":"eng"}],"arxiv":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","main_file_link":[{"open_access":"1","url":"https://doi.org/10.48550/arXiv.2408.12924"}],"date_updated":"2026-06-14T22:30:19Z","date_created":"2025-10-28T13:12:22Z","acknowledgement":"The author is thankful to Nicolas Clozeau, Lorenzo Dello Schiavo, Jan Maas, Dejan Slepčev,\r\nand Dario Trevisan for many fruitful discussions and comments. The author gratefully acknowledges support from the Austrian Science Fund (FWF) project 10.55776/F65.","title":"Asymptotics for optimal empirical quantization of measures","keyword":["optimal empirical quantization","vector quantization","Wasserstein distance","semidiscrete optimal transport","Zador’s Theorem","Pierce’s Lemma"],"publication":"arXiv","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"20563"}]},"year":"2024","date_published":"2024-08-23T00:00:00Z","status":"public","publication_status":"draft","citation":{"ista":"Quattrocchi F. Asymptotics for optimal empirical quantization of measures. arXiv, 2408.12924.","apa":"Quattrocchi, F. (n.d.). Asymptotics for optimal empirical quantization of measures. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2408.12924\">https://doi.org/10.48550/arXiv.2408.12924</a>","ama":"Quattrocchi F. Asymptotics for optimal empirical quantization of measures. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2408.12924\">10.48550/arXiv.2408.12924</a>","ieee":"F. Quattrocchi, “Asymptotics for optimal empirical quantization of measures,” <i>arXiv</i>. .","mla":"Quattrocchi, Filippo. “Asymptotics for Optimal Empirical Quantization of Measures.” <i>ArXiv</i>, 2408.12924, doi:<a href=\"https://doi.org/10.48550/arXiv.2408.12924\">10.48550/arXiv.2408.12924</a>.","short":"F. Quattrocchi, ArXiv (n.d.).","chicago":"Quattrocchi, Filippo. “Asymptotics for Optimal Empirical Quantization of Measures.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2408.12924\">https://doi.org/10.48550/arXiv.2408.12924</a>."},"corr_author":"1","OA_type":"green","language":[{"iso":"eng"}],"external_id":{"arxiv":["2408.12924"]},"author":[{"last_name":"Quattrocchi","orcid":"0009-0000-9773-1931","full_name":"Quattrocchi, Filippo","id":"3ebd6ba8-edfb-11eb-afb5-91a9745ba308","first_name":"Filippo"}]},{"publication_identifier":{"issn":["2791-4585"]},"doi":"10.15479/at:ista:17368","tmp":{"short":"CC BY-NC-SA (4.0)","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode"},"day":"13","supervisor":[{"full_name":"Robinson, Matthew Richard","orcid":"0000-0001-8982-8813","id":"E5D42276-F5DA-11E9-8E24-6303E6697425","first_name":"Matthew Richard","last_name":"Robinson"}],"_id":"17368","degree_awarded":"MS","ddc":["610"],"page":"60","department":[{"_id":"GradSch"},{"_id":"MaRo"}],"article_processing_charge":"No","oa_version":"Published Version","month":"08","type":"dissertation","language":[{"iso":"eng"}],"publication_status":"published","status":"public","year":"2024","date_published":"2024-08-13T00:00:00Z","corr_author":"1","file_date_updated":"2025-02-14T23:30:03Z","alternative_title":["ISTA Master's Thesis"],"citation":{"apa":"Villanueva Marijuan, A. (2024). <i>Bayesian linear regression for analyzing general omics data with time-to-event phenotypes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17368\">https://doi.org/10.15479/at:ista:17368</a>","ieee":"A. Villanueva Marijuan, “Bayesian linear regression for analyzing general omics data with time-to-event phenotypes,” Institute of Science and Technology Austria, 2024.","ama":"Villanueva Marijuan A. Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17368\">10.15479/at:ista:17368</a>","ista":"Villanueva Marijuan A. 2024. Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. Institute of Science and Technology Austria.","mla":"Villanueva Marijuan, Ariadna. <i>Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17368\">10.15479/at:ista:17368</a>.","short":"A. Villanueva Marijuan, Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes, Institute of Science and Technology Austria, 2024.","chicago":"Villanueva Marijuan, Ariadna. “Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17368\">https://doi.org/10.15479/at:ista:17368</a>."},"has_accepted_license":"1","author":[{"full_name":"Villanueva Marijuan, Ariadna","id":"e0ae4864-133f-11ed-8f02-adaa8dd27540","first_name":"Ariadna","last_name":"Villanueva Marijuan"}],"oa":1,"abstract":[{"text":"Recent advancements in molecular diagnostic techniques have enabled the collection of\r\nmultiple types of omics data from patients, including genomics, epigenomics, proteomics,\r\nand transcriptomics. However, we lack effective methods for integrating all these different\r\ndata types and combining them with clinical outcomes to study the molecular mechanisms\r\nthat govern pathological phenotypes. We present multi-omics BayesW, a penalized Bayesian\r\nregression method that can handle general omics data for survival analysis of time-to-event\r\nphenotypes. Our method can: (1) accommodate incomplete data by allowing censored\r\nindividuals, (2) use continuous time-to-event data to test associations of markers with a\r\nphenotype and (3) estimate effects jointly while allowing for independent groups of biological\r\nmarkers. Extensive simulations using planted signals on real data demonstrate that our model\r\naccurately retrieves the true parameters of the model while controlling for false discoveries\r\nand maintaining the expected prediction accuracy. We address data correlations by estimating\r\nthe effects jointly, even between omic groups, while also estimating the individual variance\r\nexplained by each group. We apply our model to two datasets. Using 18,000 individuals from\r\nthe Generation Scotland study we model the association of time at onset of Type 2 Diabetes,\r\nStroke, Ischemic Disease, and Osteoarthritis from baseline study entry, with 831,724 CpG\r\nmethylation probes. We find that large proportions of variation in disease onset times can\r\nbe attributed to methylation as measured in whole blood at baseline in individuals without\r\ndisease symptoms. We then apply our model to The Cancer Genome Atlas (TCGA) pan-cancer\r\ndataset, in which we use 5 types of omics: copy number variation, epigenetics, somatic\r\nmutations, miRNA, and gene expression. For cancer survival age-at-onset we find that, when\r\nfitting the 5 groups together, almost all variation attributable to \"omics\" data is explained by\r\nDNA methylation. When considering progression times, both methylation and gene expression\r\nexplain a large part of the variance. We found 2 genes that are significantly associated (95%\r\nposterior inclusion probability) with cancer survival time, conditional on all other genome-wide\r\nomics data variation. Owing to the vast variability of mechanisms characterizing different\r\ncancers, there are likely few specific genes with a strong signal in a pan-cancer setting. Taken\r\ntogether, we showed the applicability of our multi-omics BayesW model to a wide-range of\r\nbiological questions in multi-omics data.\r\n","lang":"eng"}],"file":[{"file_id":"17433","date_created":"2024-08-14T11:51:24Z","date_updated":"2025-02-14T23:30:03Z","access_level":"open_access","embargo":"2025-02-14","checksum":"0c2daa174609f0c00919dccc5701d375","relation":"main_file","content_type":"application/pdf","file_name":"Masters_thesis_AriadnaVillanueva.pdf","file_size":13052436,"creator":"avillanu"},{"creator":"avillanu","file_name":"Masters thesis-AriadnaVillanueva.zip","file_size":45642547,"relation":"source_file","content_type":"application/zip","checksum":"e9ed4465dfa539ac4c3a8d4d0b6271a1","embargo_to":"open_access","date_updated":"2025-02-14T23:30:03Z","access_level":"closed","date_created":"2024-08-14T11:51:57Z","file_id":"17434"}],"OA_place":"publisher","publisher":"Institute of Science and Technology Austria","date_created":"2024-08-02T10:52:40Z","keyword":["Epigenetics","Multi-omics","Bayesian regression"],"title":"Bayesian linear regression for analyzing general omics data with time-to-event phenotypes","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_updated":"2026-04-07T13:03:41Z"},{"article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"RySh"},{"_id":"PeJo"}],"ddc":["570"],"isi":1,"scopus_import":"1","month":"02","type":"journal_article","APC_amount":"5887,8 EUR","oa_version":"Published Version","volume":121,"_id":"15084","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"day":"20","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"doi":"10.1073/pnas.2301449121","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"article_number":"e2301449121","article_type":"original","publisher":"National Academy of Sciences","ec_funded":1,"OA_place":"publisher","file":[{"access_level":"open_access","date_updated":"2024-03-12T13:42:42Z","file_id":"15110","success":1,"date_created":"2024-03-12T13:42:42Z","file_size":13648221,"file_name":"2024_PNAS_Koppensteiner.pdf","creator":"dernst","checksum":"b25b2a057c266ff317a48b0d54d6fc8a","content_type":"application/pdf","relation":"main_file"}],"abstract":[{"text":"GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n            <jats:sup>2+</jats:sup>\r\n            -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals.","lang":"eng"}],"oa":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_updated":"2026-06-14T22:30:24Z","pmid":1,"publication":"Proceedings of the National Academy of Sciences of the United States of America","related_material":{"record":[{"status":"public","relation":"research_data","id":"13173"},{"status":"public","relation":"dissertation_contains","id":"19271"}],"link":[{"description":"News on ISTA Website","url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/","relation":"press_release"}]},"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","acknowledgement":"We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support.","date_created":"2024-03-05T09:23:55Z","citation":{"mla":"Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>.","ista":"Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 121(8), e2301449121.","apa":"Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>","ama":"Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(8). doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>","ieee":"P. Koppensteiner <i>et al.</i>, “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8. National Academy of Sciences, 2024.","chicago":"Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>.","short":"P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the United States of America 121 (2024)."},"OA_type":"hybrid","file_date_updated":"2024-03-12T13:42:42Z","corr_author":"1","status":"public","publication_status":"published","year":"2024","date_published":"2024-02-20T00:00:00Z","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"external_id":{"pmid":["38346189"],"isi":["001208567300006"]},"quality_controlled":"1","author":[{"last_name":"Koppensteiner","first_name":"Peter","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948"},{"full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep","last_name":"Bhandari"},{"first_name":"Hüseyin C","orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal"},{"first_name":"Carolina","full_name":"Borges Merjane, Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X","last_name":"Borges Merjane"},{"full_name":"Le Monnier, Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","first_name":"Elodie","last_name":"Le Monnier"},{"id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2","full_name":"Roy, Utsa","first_name":"Utsa","last_name":"Roy"},{"last_name":"Nakamura","first_name":"Yukihiro","full_name":"Nakamura, Yukihiro"},{"last_name":"Sadakata","first_name":"Tetsushi","full_name":"Sadakata, Tetsushi"},{"full_name":"Sanbo, Makoto","first_name":"Makoto","last_name":"Sanbo"},{"last_name":"Hirabayashi","full_name":"Hirabayashi, Masumi","first_name":"Masumi"},{"first_name":"JeongSeop","full_name":"Rhee, JeongSeop","last_name":"Rhee"},{"last_name":"Brose","first_name":"Nils","full_name":"Brose, Nils"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"last_name":"Shigemoto","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"}],"issue":"8","intvolume":"       121","has_accepted_license":"1"},{"page":"755-771.e9","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"ddc":["570"],"isi":1,"scopus_import":"1","article_processing_charge":"Yes (via OA deal)","month":"03","type":"journal_article","oa_version":"Published Version","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"doi":"10.1016/j.neuron.2023.12.002","day":"06","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"volume":112,"_id":"14843","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692"},{"call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232"},{"name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","grant_number":"25383","_id":"26B66A3E-B435-11E9-9278-68D0E5697425"}],"article_type":"original","PlanS_conform":"1","OA_place":"publisher","file":[{"checksum":"30098b4f0209556ddfb3540a23d07ca5","content_type":"application/pdf","relation":"main_file","file_name":"2024_Neuron_Chen.pdf","file_size":8192355,"creator":"dernst","success":1,"date_created":"2025-04-23T14:02:08Z","file_id":"19614","access_level":"open_access","date_updated":"2025-04-23T14:02:08Z"}],"abstract":[{"lang":"eng","text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission."}],"oa":1,"publisher":"Elsevier","ec_funded":1,"related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","description":"News on ISTA Website"}],"record":[{"status":"public","id":"15101","relation":"dissertation_contains"}]},"publication":"Neuron","title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","date_created":"2024-01-21T23:00:56Z","date_updated":"2026-06-14T22:30:23Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"external_id":{"pmid":["38215739"],"isi":["001202925700001"]},"quality_controlled":"1","corr_author":"1","file_date_updated":"2025-04-23T14:02:08Z","citation":{"mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024.","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9.","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9."},"OA_type":"hybrid","status":"public","publication_status":"published","year":"2024","date_published":"2024-03-06T00:00:00Z","has_accepted_license":"1","author":[{"last_name":"Chen","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, JingJing","first_name":"JingJing"},{"last_name":"Kaufmann","first_name":"Walter","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315"},{"last_name":"Chen","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","first_name":"Chong"},{"last_name":"Arai","full_name":"Arai, Itaru","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","first_name":"Itaru"},{"first_name":"Olena","orcid":"0000-0003-2344-1039","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","last_name":"Kim"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas"}],"issue":"5","intvolume":"       112"},{"degree_awarded":"PhD","supervisor":[{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692"},{"grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"grant_number":"25383","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","_id":"26B66A3E-B435-11E9-9278-68D0E5697425"}],"_id":"15101","publication_identifier":{"issn":["2663-337X"]},"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"doi":"10.15479/at:ista:15101","day":"11","oa_version":"Published Version","month":"03","type":"dissertation","article_processing_charge":"No","ddc":["570"],"page":"84","department":[{"_id":"GradSch"},{"_id":"PeJo"}],"author":[{"last_name":"Chen","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, JingJing","first_name":"JingJing"}],"has_accepted_license":"1","publication_status":"published","status":"public","year":"2024","date_published":"2024-03-11T00:00:00Z","citation":{"chicago":"Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>.","short":"J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024.","mla":"Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>.","apa":"Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>","ieee":"J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024.","ama":"Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>","ista":"Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria."},"file_date_updated":"2024-04-02T22:30:03Z","alternative_title":["ISTA Thesis"],"corr_author":"1","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_updated":"2026-04-07T13:24:22Z","date_created":"2024-03-11T10:09:54Z","related_material":{"record":[{"status":"public","id":"14843","relation":"part_of_dissertation"}]},"title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse","ec_funded":1,"publisher":"Institute of Science and Technology Austria","oa":1,"abstract":[{"text":"The coupling between presynaptic Ca2+ channels and release sensors is a key factor that\r\ndetermines speed and efficacy of synapse transmission. At some excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development, and tightening is often\r\nassociated with a switch in the reliance on different Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains unknown, and it is unclear how it changes\r\nduring development. To address this question, we analyzed the coupling configuration at the\r\ncerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of BC–PC indicated that release probability decreased, while the\r\nnumber of functional sites increased during development. Although transmitter release\r\npersistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic action potentials became shorter during development, suggesting reduced\r\nefficacy of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas docked vesicles were only clustered at later\r\ndevelopmental stages. The number of functional release sites correlated better with the AZ\r\nnumber early in development, but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling suggested a developmental transformation from a more random to a more\r\nclustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic\r\ntransmission.","lang":"eng"}],"OA_place":"publisher","file":[{"date_created":"2024-03-11T14:10:58Z","file_id":"15104","date_updated":"2024-04-02T22:30:03Z","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","embargo_to":"open_access","checksum":"db4947474ffa271e66c254b6fe876a55","creator":"jchen","file_name":"Thesis_Jingjing CHEN.docx","file_size":11271363},{"checksum":"a5eeae8b5702cd540f5d03469bc33dde","content_type":"application/pdf","relation":"main_file","file_size":16627311,"file_name":"Thesis_Jingjing CHEN_merged.pdf","creator":"jchen","file_id":"15105","date_created":"2024-03-11T14:11:06Z","date_updated":"2024-04-02T22:30:03Z","access_level":"open_access","embargo":"2024-04-01"}]},{"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"day":"11","doi":"10.15479/at:ista:18531","publication_identifier":{"issn":["2663-337X"]},"supervisor":[{"last_name":"Vicoso","first_name":"Beatriz","orcid":"0000-0002-4579-8306","full_name":"Vicoso, Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87"}],"_id":"18531","degree_awarded":"PhD","page":"181","department":[{"_id":"GradSch"},{"_id":"BeVi"}],"ddc":["576"],"article_processing_charge":"No","month":"11","type":"dissertation","oa_version":"Published Version","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"CampIT"}],"language":[{"iso":"eng"}],"file_date_updated":"2025-05-11T22:30:04Z","citation":{"mla":"Mrnjavac, Andrea. <i>Early Stages of Sex Chromosome Evolution</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18531\">10.15479/at:ista:18531</a>.","ista":"Mrnjavac A. 2024. Early stages of sex chromosome evolution. Institute of Science and Technology Austria.","ama":"Mrnjavac A. Early stages of sex chromosome evolution. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18531\">10.15479/at:ista:18531</a>","ieee":"A. Mrnjavac, “Early stages of sex chromosome evolution,” Institute of Science and Technology Austria, 2024.","apa":"Mrnjavac, A. (2024). <i>Early stages of sex chromosome evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18531\">https://doi.org/10.15479/at:ista:18531</a>","chicago":"Mrnjavac, Andrea. “Early Stages of Sex Chromosome Evolution.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18531\">https://doi.org/10.15479/at:ista:18531</a>.","short":"A. Mrnjavac, Early Stages of Sex Chromosome Evolution, Institute of Science and Technology Austria, 2024."},"alternative_title":["ISTA Thesis"],"corr_author":"1","status":"public","publication_status":"published","date_published":"2024-11-11T00:00:00Z","year":"2024","has_accepted_license":"1","author":[{"last_name":"Mrnjavac","first_name":"Andrea","id":"353FAC84-AE61-11E9-8BFC-00D3E5697425","full_name":"Mrnjavac, Andrea"}],"OA_embargo":"6","abstract":[{"text":"Sex chromosomes and autosomes exhibit very different evolutionary dynamics.\r\nThe Y chromosome usually degenerates, leaving many X-linked loci hemizygous in\r\nmales. Since recessive X-linked mutations are always exposed to selection in males,\r\nselection is more efficient on the X chromosome than on autosomes on recessive\r\nmutations, leading to faster adaptation on the X chromosome than other genomic\r\nregions, if beneficial mutations are on average recessive (known as the Faster-X\r\neffect). In the presence of the functional, but non-recombining gametolog on the Y (as\r\nis often the case in young non-recombining regions), recessive mutations are\r\nsheltered from selection on the X chromosome. We model this scenario and show that\r\nthe efficiency of selection is reduced on diploid X loci due to sheltering by the Y\r\nchromosome. Reduced efficiency of selection leads to slower adaptation and\r\nincreased accumulation of deleterious mutations (Slower-X effect). We extended this\r\nmodel to explore the effect of sex-specific selection on degeneration of sex\r\nchromosomes, showing theoretically that male-limited genes degenerate on the X\r\nchromosome and female-biased genes degenerate on the Y chromosome. This\r\nprediction depends on the effective population size and the mutation rate, explaining\r\nthe variety of sex chromosome degeneration patterns observed in nature.\r\nTo test for direct evidence of a Slower-X (or Slower-Z) effect, we analyzed the\r\nZW sex chromosomes of the flatworm Schistosoma japonicum, which have a very\r\nyoung non-recombining region with non-degenerated W. Diploid Z-linked genes have\r\nhigher ratios of non-synonymous to synonymous polymorphisms than autosomal\r\ngenes, supporting reduced efficiency of selection on the diploid Z region. These results\r\nprovide evidence of sheltering by the W chromosome, a mechanism that could\r\ncontribute to Z (X) chromosome degeneration, and illustrate contrasting evolutionary\r\npatterns in old and young sex chromosome regions. In addition, genes with sexspecific patterns of expression show opposite patterns of selection in the young\r\n(diploid) and old (hemizygous) Z, showing the complex manner in which sex-specific selection shapes the evolutionary patterns of sex chromosomes. ","lang":"eng"}],"file":[{"checksum":"3e48b163c22114ef5d5371f758668289","embargo_to":"open_access","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":26870629,"file_name":"AMrnjavac_thesis_library.docx","creator":"amrnjava","file_id":"18551","date_created":"2024-11-13T12:15:28Z","title":"Early stages of sex chromosome evolution","access_level":"closed","date_updated":"2025-05-11T22:30:04Z"},{"checksum":"3ead60c1b678e7dcf018043aef3b5db2","relation":"main_file","content_type":"application/pdf","file_size":4228766,"file_name":"AMrnjavac_thesis_library.pdf","creator":"amrnjava","date_created":"2024-11-13T12:15:54Z","file_id":"18552","title":"Early stages of sex chromosome evolution","access_level":"open_access","date_updated":"2025-05-11T22:30:04Z","embargo":"2025-05-11"}],"OA_place":"publisher","oa":1,"publisher":"Institute of Science and Technology Austria","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"12521"},{"relation":"part_of_dissertation","id":"18549","status":"public"}]},"keyword":["Sex chromosomes","evolution","selection","sheltering"],"title":"Early stages of sex chromosome evolution","date_created":"2024-11-11T08:40:45Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_updated":"2026-04-07T13:22:45Z"},{"degree_awarded":"PhD","_id":"18661","supervisor":[{"orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","first_name":"Anđela","last_name":"Šarić"}],"publication_identifier":{"isbn":["978-3-99078-046-6"],"issn":["2663-337X"]},"day":"17","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","image":"/images/cc_by_sa.png","name":"Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0)","short":"CC BY-SA (4.0)"},"doi":"10.15479/at:ista:18661","oa_version":"Published Version","type":"dissertation","month":"12","article_processing_charge":"No","ddc":["572","530"],"department":[{"_id":"GradSch"},{"_id":"AnSa"}],"page":"57","license":"https://creativecommons.org/licenses/by-sa/4.0/","author":[{"last_name":"Santana de Freitas Amaral","first_name":"Miguel","id":"4f2d02dd-47a9-11ec-ad10-82820ed3f501","full_name":"Santana de Freitas Amaral, Miguel"}],"has_accepted_license":"1","year":"2024","date_published":"2024-12-17T00:00:00Z","publication_status":"published","status":"public","citation":{"short":"M. Santana de Freitas Amaral, Archaeal Membranes : In Silico Modelling and Design, Institute of Science and Technology Austria, 2024.","chicago":"Santana de Freitas Amaral, Miguel. “Archaeal Membranes : In Silico Modelling and Design.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18661\">https://doi.org/10.15479/at:ista:18661</a>.","apa":"Santana de Freitas Amaral, M. (2024). <i>Archaeal membranes : In silico modelling and design</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18661\">https://doi.org/10.15479/at:ista:18661</a>","ieee":"M. Santana de Freitas Amaral, “Archaeal membranes : In silico modelling and design,” Institute of Science and Technology Austria, 2024.","ama":"Santana de Freitas Amaral M. Archaeal membranes : In silico modelling and design. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18661\">10.15479/at:ista:18661</a>","ista":"Santana de Freitas Amaral M. 2024. Archaeal membranes : In silico modelling and design. Institute of Science and Technology Austria.","mla":"Santana de Freitas Amaral, Miguel. <i>Archaeal Membranes : In Silico Modelling and Design</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18661\">10.15479/at:ista:18661</a>."},"corr_author":"1","alternative_title":["ISTA Thesis"],"file_date_updated":"2025-06-18T22:30:03Z","language":[{"iso":"eng"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_updated":"2026-04-07T13:22:29Z","date_created":"2024-12-16T10:53:39Z","title":"Archaeal membranes : In silico modelling and design","related_material":{"record":[{"relation":"part_of_dissertation","id":"18670","status":"public"}]},"publisher":"Institute of Science and Technology Austria","oa":1,"file":[{"file_id":"18671","date_created":"2024-12-18T12:27:01Z","date_updated":"2025-06-18T22:30:03Z","access_level":"closed","checksum":"eca06497a29078558395455c890a32d9","embargo_to":"open_access","content_type":"application/zip","relation":"source_file","file_size":19161387,"file_name":"2024_msfa_thesis.zip","creator":"mamaral"},{"file_size":16530084,"file_name":"2024_msfa_thesis.pdf","creator":"mamaral","checksum":"2dc30ea46c5daf48d07e4cccb3c3de00","relation":"main_file","content_type":"application/pdf","access_level":"open_access","date_updated":"2025-06-18T22:30:03Z","embargo":"2025-06-18","file_id":"18672","date_created":"2024-12-18T12:26:30Z"}],"abstract":[{"text":"Across the tree of life, distinct designs of cellular membranes have evolved that are both stable\r\nand flexible. In bacteria and eukaryotes this trade-off is accomplished by single-headed lipids\r\nthat self-assemble into flexible bilayer membranes. By contrast, archaea in many cases possess\r\nboth bilayer and double-headed, monolayer spanning bolalipids. This composition is believed\r\nto enable extremophile archaea to survive harsh environments. Here, through the creation of a\r\nminimal computational model for bolalipid membranes, we discover trade-offs when forming\r\nmembranes using lipids of a single type. Similar to living archaea, we can tune the stiffness of\r\nbolalipid molecules. We find that membranes made out of flexible bolalipid molecules resemble\r\nbilayer membranes as they can adopt U-shaped conformations to enable higher curvatures.\r\nConversely, rigid bolalipid molecules, like those found in archaea at higher temperatures,\r\npreferentially take on a straight conformation to self-assemble into liquid membranes that are\r\nstable, stiff, prone to pore formation, and which tear during membrane reshaping. Strikingly,\r\nhowever, our analysis reveals that it is possible to achieve the best of both worlds – membranes\r\nthat are fluid, stable at high temperatures and flexible enough to be reshaped without leaking –\r\nthrough the inclusion of a small fraction of bilayer lipids into a bolalipid membrane. Additionally,\r\nthe curvature-dependent softening of bolalipid membranes made of lipids with tension-sensitive\r\nconformation can also enable high rigidity at low curvatures while softening at high curvatures,\r\nmaking the membrane effectively a plastic material. Taken together, our study compares the\r\ndifferent membrane designs across the tree of life and indicates how combining lipids can be\r\nused to resolve trade-offs when generating membranes for (bio)technological applications.\r\n","lang":"eng"}],"OA_place":"publisher"},{"project":[{"call_identifier":"H2020","_id":"eba2549b-77a9-11ec-83b8-a81e493eae4e","grant_number":"802960","name":"Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines"}],"_id":"18670","date_published":"2024-11-27T00:00:00Z","year":"2024","status":"public","publication_status":"draft","citation":{"mla":"Santana de Freitas Amaral, Miguel, et al. “Stability vs Flexibility: Reshaping Archaeal Membranes in Silico.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.10.18.619072\">10.1101/2024.10.18.619072</a>.","ista":"Santana de Freitas Amaral M, Frey FF, Jiang X, Baum B, Šarić A. Stability vs flexibility: Reshaping archaeal membranes in silico. bioRxiv, <a href=\"https://doi.org/10.1101/2024.10.18.619072\">10.1101/2024.10.18.619072</a>.","ieee":"M. Santana de Freitas Amaral, F. F. Frey, X. Jiang, B. Baum, and A. Šarić, “Stability vs flexibility: Reshaping archaeal membranes in silico,” <i>bioRxiv</i>. .","ama":"Santana de Freitas Amaral M, Frey FF, Jiang X, Baum B, Šarić A. Stability vs flexibility: Reshaping archaeal membranes in silico. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.10.18.619072\">10.1101/2024.10.18.619072</a>","apa":"Santana de Freitas Amaral, M., Frey, F. F., Jiang, X., Baum, B., &#38; Šarić, A. (n.d.). Stability vs flexibility: Reshaping archaeal membranes in silico. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.10.18.619072\">https://doi.org/10.1101/2024.10.18.619072</a>","chicago":"Santana de Freitas Amaral, Miguel, Felix F Frey, Xiuyun Jiang, Buzz Baum, and Anđela Šarić. “Stability vs Flexibility: Reshaping Archaeal Membranes in Silico.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.10.18.619072\">https://doi.org/10.1101/2024.10.18.619072</a>.","short":"M. Santana de Freitas Amaral, F.F. Frey, X. Jiang, B. Baum, A. Šarić, BioRxiv (n.d.)."},"corr_author":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"day":"27","doi":"10.1101/2024.10.18.619072","language":[{"iso":"eng"}],"author":[{"id":"4f2d02dd-47a9-11ec-ad10-82820ed3f501","full_name":"Santana de Freitas Amaral, Miguel","first_name":"Miguel","last_name":"Santana de Freitas Amaral"},{"last_name":"Frey","id":"a0270b37-8f1a-11ec-95c7-8e710c59a4f3","full_name":"Frey, Felix F","orcid":"0000-0001-8501-6017","first_name":"Felix F"},{"last_name":"Jiang","full_name":"Jiang, Xiuyun","first_name":"Xiuyun"},{"last_name":"Baum","first_name":"Buzz","full_name":"Baum, Buzz"},{"id":"bf63d406-f056-11eb-b41d-f263a6566d8b","full_name":"Šarić, Anđela","orcid":"0000-0002-7854-2139","first_name":"Anđela","last_name":"Šarić"}],"ec_funded":1,"article_processing_charge":"No","oa":1,"OA_place":"repository","abstract":[{"lang":"eng","text":"Across the tree of life, distinct designs of cellular membranes have evolved. In bacteria and eukaryotes single-headed lipids self-assemble into flexible bilayer membranes. By contrast, archaea often possess double-headed, monolayer spanning bolalipids, mixed with bilayer lipids, enabling them to survive in harsh environments. Here, using a minimal computational model for bolalipid membranes, we discover trade-offs when forming membranes. We find that membranes made out of flexible bolalipids resemble bilayer membranes as bolalipids exhibit conformational switch into U-shaped conformations to enable higher curvatures. Conversely, stiffer bolalipids, resembling those in extremophile archaea, take on straight conformations and form liquid membranes that are stiff, and prone to pore formation during membrane reshaping. Strikingly, we show how to achieve fluid bolalipid membranes that are both stable and flexible – by including small amounts of bilayer lipids, as archaea do. Our study explains how different organisms resolve trade-offs when generating membranes of desired material properties."}],"department":[{"_id":"AnSa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2026-06-14T22:30:26Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2024.10.18.619072"}],"date_created":"2024-12-18T10:07:45Z","oa_version":"Preprint","acknowledgement":"MA, BB, and AŠ acknowledge funding by the\r\nVolkswagen Foundation Grant Az 96727. FF\r\nacknowledges fnancial support by the NOMIS\r\nfoundation. AŠ acknowledges funding by ERC\r\nStarting Grant “NEPA” 802960. We thank\r\nClaudia Flandoli for help with illustrations.","title":"Stability vs flexibility: Reshaping archaeal membranes in silico","type":"preprint","month":"11","related_material":{"record":[{"id":"18661","relation":"dissertation_contains","status":"public"}]},"publication":"bioRxiv"},{"day":"04","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"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"},"doi":"10.1101/2024.07.02.601697","language":[{"iso":"eng"}],"citation":{"short":"A. Mrnjavac, B. Vicoso, BioRxiv (n.d.).","chicago":"Mrnjavac, Andrea, and Beatriz Vicoso. “Evidence of a Slower-Z Effect in Schistosoma Japonicum.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.07.02.601697\">https://doi.org/10.1101/2024.07.02.601697</a>.","ista":"Mrnjavac A, Vicoso B. Evidence of a Slower-Z effect in Schistosoma japonicum. bioRxiv, <a href=\"https://doi.org/10.1101/2024.07.02.601697\">10.1101/2024.07.02.601697</a>.","ama":"Mrnjavac A, Vicoso B. Evidence of a Slower-Z effect in Schistosoma japonicum. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.07.02.601697\">10.1101/2024.07.02.601697</a>","ieee":"A. Mrnjavac and B. Vicoso, “Evidence of a Slower-Z effect in Schistosoma japonicum,” <i>bioRxiv</i>. .","apa":"Mrnjavac, A., &#38; Vicoso, B. (n.d.). Evidence of a Slower-Z effect in Schistosoma japonicum. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.07.02.601697\">https://doi.org/10.1101/2024.07.02.601697</a>","mla":"Mrnjavac, Andrea, and Beatriz Vicoso. “Evidence of a Slower-Z Effect in Schistosoma Japonicum.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.07.02.601697\">10.1101/2024.07.02.601697</a>."},"corr_author":"1","_id":"18549","date_published":"2024-07-04T00:00:00Z","year":"2024","status":"public","publication_status":"draft","author":[{"last_name":"Mrnjavac","id":"353FAC84-AE61-11E9-8BFC-00D3E5697425","full_name":"Mrnjavac, Andrea","first_name":"Andrea"},{"last_name":"Vicoso","first_name":"Beatriz","orcid":"0000-0002-4579-8306","full_name":"Vicoso, Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"BeVi"}],"abstract":[{"lang":"eng","text":"Sex-linked and autosomal loci experience different selective pressures and\r\nevolutionary dynamics. X (or Z) chromosomes are often hemizygous, as Y (or W)\r\nchromosomes often degenerate. Such hemizygous regions can be under greater\r\nefficacy of selection, as recessive mutations are immediately exposed to selection in\r\nthe heterogametic sex (the so-called Faster-X or Faster-Z effect). However, in young\r\nnon-recombining regions, Y/W chromosomes often have many functional genes, and\r\nmany X/Z-linked loci are therefore diploid. The sheltering of recessive mutations on\r\nthe X/Z by the Y/W homolog is expected to drive a Slower-X (Slower-Z) effect for\r\ndiploid X/Z loci, i.e. a reduction in the efficacy of selection. While the Faster-X effect\r\nhas been studied extensively, much less is known empirically about the evolutionary\r\ndynamics of diploid X or Z chromosomes. Here, we took advantage of published\r\npopulation genomic data in the female-heterogametic human parasite Schistosoma\r\njaponicum to characterize the gene content and diversity levels of the diploid and\r\nhemizygous regions of the Z chromosome. We used different metrics of selective\r\npressures acting on genes to test for differences in the efficacy of selection in\r\nhemizygous and diploid Z regions, relative to autosomes. We found consistent\r\npatterns suggesting reduced Ne, and reduced efficacy of purifying selection, on both\r\nhemizygous and diploid Z regions. Moreover, relaxed selection was particularly\r\npronounced for female-biased genes on the diploid Z, as predicted by Slower-Z\r\ntheory.\r\n"}],"OA_place":"repository","oa":1,"article_processing_charge":"No","title":"Evidence of a Slower-Z effect in Schistosoma japonicum","type":"preprint","publication":"bioRxiv","month":"07","related_material":{"record":[{"status":"public","id":"19370","relation":"later_version"},{"status":"public","relation":"dissertation_contains","id":"18531"}]},"date_created":"2024-11-13T09:12:08Z","oa_version":"Preprint","date_updated":"2026-06-14T22:30:25Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","main_file_link":[{"url":"https://doi.org/10.1101/2024.07.02.601697","open_access":"1"}]}]