@inproceedings{22831, abstract = {Neural models learn representations of high-dimensional data on low-dimensional manifolds. Multiple factors, including stochasticities in the training process, model architectures, and additional inductive biases, may induce different representations, even when learning the same task on the same data. However, it has recently been shown that when a latent structure is shared between distinct latent spaces, relative distances between representations can be preserved, up to distortions. Building on this idea, we demonstrate that exploiting the differential-geometric structure of latent spaces of neural models, it is possible to capture precisely the transformations between representational spaces trained on similar data distributions. Specifically, we assume that distinct neural models parametrize approximately the same underlying manifold, and introduce a representation based on the pullback metric that captures the intrinsic structure of the latent space, while scaling efficiently to large models. We validate experimentally our method on model stitching and retrieval tasks, covering autoencoders and vision foundation discriminative models, across diverse architectures, datasets, pretraining schemes and modalities. Code is available at https://github.com/marc0git/RelativeGeodesics.}, author = {Yu, Hanlin and Inal, Berfin and Arvanitidis, Georgios and Hauberg, Søren and Locatello, Francesco and Fumero, Marco}, booktitle = {39th Conference on Neural Information Processing Systems}, isbn = {9798331338275}, issn = {1049-5258}, location = {San Diego, CA, United States}, pages = {125316--125360}, publisher = {Neural Information Processing Systems Foundation}, title = {{Connecting neural models latent geometries with relative geodesic representations}}, doi = {10.52202/085713-3769}, volume = {38}, year = {2025}, } @article{22929, abstract = {The circle method has been successfully used over the last century to study rational points on hypersurfaces. More recently, a version of the method over function fields, combined with spreading out techniques, has led to a range of results about moduli spaces of rational curves on hypersurfaces. In this paper a version of the circle method is implemented in the setting of the Grothendieck ring of varieties. This allows us to approximate the classes of these moduli spaces directly, without relying on point counting, and leads to a deeper understanding of their geometry.}, author = {Bilu, Margaret and Browning, Timothy D}, issn = {1873-2151}, journal = {Annales Scientifiques de l’École Normale Supérieure}, keywords = {Circle method, moduli spaces of curves, hypersurfaces, Grothendieck ring of varieties, motivic integration}, number = {5}, pages = {1179--1242}, publisher = {Société Mathématique de France}, title = {{A motivic circle method}}, doi = {10.24033/asens.2628}, volume = {58}, year = {2025}, } @article{18449, abstract = {Research involving human subjects or identifiable human material and data must be assessed by an ethics committee. The Karl Landsteiner University of Health Sciences has established a Commission on Ethics and Scientific Integrity to evaluate medical research conducted by its faculty and students and at its affiliated hospitals. All projects submitted to the Commission on Ethics and Scientific Integrity between 2018 and 2023 were analyzed regarding their major characteristics, the duration of the evaluation process, and votes issued. A total of 520 applications were electronically submitted during the observation period. Most of the studies were retrospective data analyses in the field of oncology, psychology and surgery. Most studies included less than 100 volunteers. Of the applications 50% received a final vote within 5 months, during which several revision rounds took place. Overall, about 77% of votes issued during the observation period were positive and 2% were rejections. In 11% files were closed due to withdrawal. In 11% final votes were pending at the end of the observation period due to requests for revisions. Our results emphasize the importance of institutional ethics committees using the example of the Commission on Ethics and Scientific Integrity at the Karl Landsteiner University. Such committees fill a gap in evaluating research not covered by Austrian legal regulations. Continuous development of standards, operating procedures, and national and international collaborations are required to assess and minimize risks to trial subjects and to provide a safe and productive environment for research in human medicine and related fields.}, author = {Schober, Sophie and Klee, Sascha and Trautinger, Franz}, issn = {1613-7671}, journal = {Wiener Klinische Wochenschrift}, pages = {432--437}, publisher = {Springer Nature}, title = {{The role of institutional ethics committees in Austria: Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018–2023}}, doi = {10.1007/s00508-024-02462-x}, volume = {137}, year = {2025}, } @article{17240, abstract = {We prove an upper bound on the energy density of the dilute spin-\(\frac {1}{2}\) Fermi gas capturing the leading correction to the kinetic energy\(8\pi a\rho _\uparrow\rho _\downarrow\) with an error of size smaller than\(a\rho^{2}(a^ 3\rho)^{1/3-\varepsilon}\) for any\(\varepsilon> 0\), where a denotes the scattering length of the interaction. The result is valid for a large class of interactions including interactions with a hard core. A central ingredient in the proof is a rigorous version of a fermionic cluster expansion adapted from the formal expansion of Gaudin et al. (Nucl Phys A 176(2):237–260, 1971. https://doi.org/10.1016/0375-9474(71)90267-3).}, author = {Lauritsen, Asbjørn Bækgaard}, issn = {1424-0637}, journal = {Annales Henri Poincare}, pages = {203--243}, publisher = {Springer Nature}, title = {{Almost optimal upper bound for the ground state energy of a dilute Fermi gas via cluster expansion}}, doi = {10.1007/s00023-024-01450-1}, volume = {26}, year = {2025}, } @article{18074, abstract = {The Aharonov–Casher theorem is a result on the number of the so-called zero modes of a system described by the magnetic Pauli operator in R2. In this paper we address the same question for the Dirac operator on a flat two-dimensional manifold with boundary and Atiyah–Patodi–Singer boundary condition. More concretely we are interested in the plane and a disc with a finite number of circular holes cut out. We consider a smooth compactly supported magnetic field on the manifold and an arbitrary magnetic field inside the holes.}, author = {Fialova, Marie}, issn = {1424-0637}, journal = {Annales Henri Poincare}, pages = {2859--2900}, publisher = {Springer Nature}, title = {{Aharonov–Casher theorems for Dirac operators on manifolds with boundary and APS boundary condition}}, doi = {10.1007/s00023-024-01482-7}, volume = {26}, year = {2025}, } @article{17293, abstract = {Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of CaV2.1 channels in the hippocampus in association with GABAB receptors. Histoblotting experiments showed that the density of CaV2.1 channel was significantly reduced in the hippocampus of APP/PS1 mice in a laminar-dependent manner. CaV2.1 channel was enriched in the active zone of the axon terminals and was present at a very low density over the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the density of CaV2.1 channel in the active zone was significantly reduced in the strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum oriens. The decline in Cav2.1 channel density was found to be associated with a corresponding impairment in the GABAergic synaptic function, as evidenced by electrophysiological experiments carried out in the hippocampus of APP/PS1 mice. Remarkably, double SDS-FRL showed a co-clustering of CaV2.1 channel and GABAB1 receptor in nanodomains (~40–50 nm) in wild type mice, while in APP/PS1 mice this nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced reduction in CaV2.1 channel density and CaV2.1-GABAB1 de-clustering may play a role in the synaptic transmission alterations shown in the AD hippocampus. Therefore, uncovering these layer-dependent changes in P/Q calcium currents associated with AD pathology can benefit the development of future strategies for AD management.}, author = {Martín‐Belmonte, Alejandro and Aguado, Carolina and Alfaro‐Ruiz, Rocío and Kulik, Akos and de la Ossa, Luis and Moreno‐Martínez, Ana Esther and Alberquilla, Samuel and García‐Carracedo, Lucía and Fernández, Miriam and Fajardo‐Serrano, Ana and Aso, Ester and Shigemoto, Ryuichi and Martín, Eduardo D. and Fukazawa, Yugo and Ciruela, Francisco and Luján, Rafael}, issn = {1750-3639}, journal = {Brain Pathology}, number = {2}, publisher = {Wiley}, title = {{Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology}}, doi = {10.1111/bpa.13279}, volume = {35}, year = {2025}, } @inproceedings{20292, abstract = {In automated decision-making, it is desirable that outputs of decision-makers be robust to slight perturbations in their inputs, a property that may be called input-output robustness. Input-output robustness appears in various different forms in the literature, such as robustness of AI models to adversarial or semantic perturbations and individual fairness of AI models that make decisions about humans. We propose runtime monitoring of input-output robustness of deployed, black-box AI models, where the goal is to design monitors that would observe one long execution sequence of the model, and would raise an alarm whenever it is detected that two similar inputs from the past led to dissimilar outputs. This way, monitoring will complement existing offline ''robustification'' approaches to increase the trustworthiness of AI decision-makers. We show that the monitoring problem can be cast as the fixed-radius nearest neighbor (FRNN) search problem, which, despite being well-studied, lacks suitable online solutions. We present our tool Clemont, which offers a number of lightweight monitors, some of which use upgraded online variants of existing FRNN algorithms, and one uses a novel algorithm based on binary decision diagrams--a data-structure commonly used in software and hardware verification. We have also developed an efficient parallelization technique that can substantially cut down the computation time of monitors for which the distance between input-output pairs is measured using the L∞norm. Using standard benchmarks from the literature of adversarial and semantic robustness and individual fairness, we perform a comparative study of different monitors in Clemont, and demonstrate their effectiveness in correctly detecting robustness violations at runtime.}, author = {Gupta, Ashutosh and Henzinger, Thomas A and Kueffner, Konstantin and Mallik, Kaushik and Pape, David}, booktitle = {Proceedings of the 31st ACM SIGKDD Conference on Knowledge Discovery and Data Mining}, isbn = {9798400714542}, issn = {2154-817X}, location = {Toronto, Canada}, pages = {790--801}, publisher = {Association for Computing Machinery}, title = {{Monitoring robustness and individual fairness}}, doi = {10.1145/3711896.3737054}, volume = {2}, year = {2025}, } @inproceedings{21090, abstract = {Fairness in AI is traditionally studied as a static property evaluated once, over a fixed dataset. However, real-world AI systems operate sequentially, with outcomes and environments evolving over time. This paper proposes a framework for analysing fairness as a runtime property. Using a minimal yet expressive model based on sequences of coin tosses with possibly evolving biases, we study the problems of monitoring and enforcing fairness expressed in either toss outcomes or coin biases. Since there is no one-size-fits-all solution for either problem, we provide a summary of monitoring and enforcement strategies, parametrised by environment dynamics, prediction horizon, and confidence thresholds. For both problems, we present general results under simple or minimal assumptions. We survey existing solutions for the monitoring problem for Markovian and additive dynamics, and existing solutions for the enforcement problem in static settings with known dynamics.}, author = {Cano Cordoba, Filip and Henzinger, Thomas A and Kueffner, Konstantin}, booktitle = {25th International Conference on Runtime Verification}, issn = {1611-3349}, location = {Graz, Austria}, pages = {1--21}, publisher = {Springer Nature}, title = {{Algorithmic fairness: A runtime perspective}}, doi = {10.1007/978-3-032-05435-7_1}, volume = {16087}, year = {2025}, } @phdthesis{20357, author = {Ruzickova, Natalia}, isbn = {978-3-99078-066-4}, issn = {2663-337X}, keywords = {gene regulation, networks, omnigenic model, pancreas, collective behaviour}, pages = {156}, publisher = {Institute of Science and Technology Austria}, title = {{Effect propagation in biological networks}}, doi = {10.15479/AT-ISTA-20357}, year = {2025}, } @unpublished{21427, abstract = {While tumor malignancy has been extensively studied under the prism of genetic and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal interactions with the microenvironment. This raises the hitherto untested possibility that heterogeneity of the untransformed tumor stroma can actively fuel malignant progression. As biological heterogeneity is inherently difficult to control, we adopted a reductionist approach and let tumor cells invade micro-engineered environments harboring obstacles with precision-controlled geometry. We find that not only the presence of obstacles, but more surprisingly their spatial disorder, causes a drastic shift from a collective to a single-cell mode of invasion – comparable in strength to cadherin loss. Combining live-imaging and perturbation experiments with minimal biophysical modeling, we demonstrate that cell detachments result both from local geometrical constraints and a global integration of spatial disorder over time. We show that different types of microenvironments map onto different universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with quenched disorder (KPZq). Our findings highlight generic physical principles for how the mode of cancer cell invasion depends on environmental heterogeneity, with potential implications to understand tumor evolution in vivo.}, author = {Dunajova, Zuzana and Tasciyan, Saren and Majek, Juraj and Merrin, Jack and Sahai, Erik and Sixt, Michael K and Hannezo, Edouard B}, booktitle = {bioRxiv}, title = {{Substrate heterogeneity promotes cancer cell dissemination through interface roughening}}, doi = {10.1101/2025.05.20.655037}, year = {2025}, } @phdthesis{20117, author = {Wang, Yiqun}, issn = {2663-337X}, pages = {108}, publisher = {Institute of Science and Technology Austria}, title = {{The role of dynamin related protein 2A in cytokinin regulated plant growth and development}}, doi = {10.15479/AT-ISTA-20117}, year = {2025}, } @phdthesis{20212, author = {Miranda, Osvaldo}, isbn = {978-3-99078-063-3}, issn = {2663-337X}, keywords = {Pten, mtor, cortical development, MADM, Mapk}, pages = {119}, publisher = {Institute of Science and Technology Austria}, title = {{Unraveling the role of Pten in cortical stem cell lineage progression using MADM}}, doi = {10.15479/AT-ISTA-20212}, year = {2025}, } @phdthesis{19386, abstract = {Crustaceans are a large group of arthropods with a great diversity of species and different types of sex determination systems and reproductive modes (Subramoniam, 2017). This makes them a great model for exploring the evolution of sex chromosomes and sexual dimorphism and investigating the evolutionary mechanisms driving and maintaining the diversity of reproductive systems. Within this taxon, Brine shrimp of the genus Artemia, a branchiopod crustacean, are well suited for such explorations, as they have both highly dimorphic traits and closely related sexual and asexual species. Although brine shrimp are known to have ZW sex chromosomes (Bowen, 1963; Parraguez et al., 2009), the sex chromosomes are still not well characterized at the genomic level, the sex-determination gene is unknown, and it is still unclear whether the same sex chromosomes as shared by the different species. The first part of this thesis was to characterize the Z and W chromosomes in Artemia using an array of methods, from generating multiple chromosome and contig level genome assemblies to identifying W-linked scaffolds and transcripts in multiple species using k-mer based approaches. The second part tackles the conservation of the cell type specific regulatory pathways in the female reproductive system between Artemia and Drosophila, and the expression of the Z-specific region throughout meiosis using single-nucleus RNA-seq data. Our results show that germline cells lack dosage compensation, with a subset of cells showing evidence of extreme repression of the Z chromosome. With multiple sexual species and several asexual lineages of parthenogenetic females that produce rare males at low frequencies, Brine shrimp present the perfect opportunity to explore the transition to asexuality and shed light on the prerequisites and repercussions of the form of modified meiosis maintaining the asexual lineages. The last chapter is an investigation of the molecular pathways involved in asexual reproduction in Artemia using newly generated single nucleus RNAseq and WGS data and previously published data. }, author = {Elkrewi, Marwan N}, isbn = {9783990780534}, issn = {2663-337X}, pages = {170}, publisher = {Institute of Science and Technology Austria}, title = {{Evolution of sex chromosomes, sex determination and asexuality in Artemia brine shrimp}}, doi = {10.15479/AT-ISTA-19386}, year = {2025}, } @phdthesis{20798, abstract = {Atom interferometers measure the relative phase shifts between coherent matter-wave paths that arise from interactions with external fields or inertial forces. Due to their exceptional phase sensitivity, atom interferometers became an essential tool for precision measurements and fundamental physics experiments, finding applications in geodesy, gravimetry, and inertial navigation. However, their measurement precision is limited by quantum projection noise, which arises from the Heisenberg uncertainty principle, preventing the measurement of atomic states with absolute precision. The generation of entanglement between the atoms offers a path to surpass this so-called standard quantum limit, thereby enhancing the interferometer’s phase sensitivity beyond classical measurement bounds. This thesis reports on the development of an atom interferometer experiment designed to realize cavity-mediated, squeezed Mach-Zehnder-type interferometry with ultra-cold 87Rb atoms. The experiment combines cavity-aided spin-squeezing with cavity-mediated Mach-Zehnder interferometry to demonstrate entanglement-enhanced phase sensitivity. The experiment is centered on a triangular optical cavity that mediates all relevant atom-light interactions. The cavity provides optical trapping, spin-squeezing, and Raman beam-splitter operations, enabling to perform interferometry on a continuously trapped atomic ensemble. The thesis elaborates on the fundamental theoretical framework, the cavity design, and the full optical setup, including the detailed configuration of the developed laser stabilization methods. Experimentally, continuous loading methods were explored, resulting in an accumulation of up to 4 × 106 atoms in the dipole trap within a cycle time of 500 ms. The AC Stark shift compensation method developed for continuous loading was further applied for in-trap cooling to 10 µK, and optical pumping for efficient atomic state preparation. Coherent state control was verified via observation of microwave-driven Rabi oscillations, and used to characterize atom-cavity coupling. These presented results establish the experimental groundwork for the future development of cavity-mediated, entanglement-enhanced Mach-Zehnder-type atom interferometry.}, author = {Wald, Sebastian}, isbn = {978-3-99078-075-6}, issn = {2663-337X}, keywords = {entanglement-enhanced atom interferometry, cavity QED, spin-squeezing, dipole trap, quantum optics}, pages = {152}, publisher = {Institute of Science and Technology Austria}, title = {{Atoms in a propagating-wave cavity for squeezed Mach-Zehnder atom interferometry}}, doi = {10.15479/AT-ISTA-20798}, year = {2025}, } @article{19498, abstract = {A dynamic interplay between fast synaptic signals and slower neuromodulatory signals controls the excitatory/inhibitory (E/I) balance within neuronal circuits. The mechanisms by which neuropeptide signaling is regulated to maintain E/I balance remain uncertain. We designed a genetic screen to isolate genes involved in the peptidergic maintenance of the E/I balance in the C. elegans motor circuit. This screen identified the C. elegans orthologs of the presynaptic phosphoprotein synapsin (snn-1) and the protein phosphatase 1 (PP1) regulatory subunit PHACTR1 (phac-1). We demonstrate that both phac-1 and snn-1 alter the motor behavior of C. elegans, and genetic interactions suggest that SNN-1 contributes to PP1-PHAC-1 holoenzyme signaling. De novo variants of human PHACTR1, associated with early-onset epilepsies [developmental and epileptic encephalopathy 70 (DEE70)], when expressed in C. elegans resulted in constitutive PP1-PHAC-1 holoenzyme activity. Unregulated PP1-PHAC-1 signaling alters the synapsin and actin cytoskeleton and increases neuropeptide release by cholinergic motor neurons, which secondarily affects the presynaptic vesicle cycle. Together, these results clarify the dominant mechanisms of action of the DEE70 alleles and suggest that altered neuropeptide release may alter E/I balance in DEE70.}, author = {Stratigi, Aikaterini and Soler-García, Miguel and Krout, Mia and Shukla, Shikha and De Bono, Mario and Richmond, Janet E. and Laurent, Patrick}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {13}, publisher = {Society for Neuroscience}, title = {{Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans}}, doi = {10.1523/JNEUROSCI.1767-23.2024}, volume = {45}, year = {2025}, } @phdthesis{18871, abstract = {"Can we do this with a new type of computer - a quantum computer?". This famous quotation of the brilliant Richard Feynman within a conference talk on "Simulating physics with computers.” is often reverently praised as the origin of the field of quantum computing. The idea was to use quantum mechanical systems itself to simulate "Nature", which is inherently quantum mechanical. Now, 43 years later, the theoretical framework of how such a computer can operate has been developed. Two main important concepts for a potential quantum supremacy, superposition and entanglement, have been exploited to design quantum algorithms to significantly speed up certain tasks. Yet, the specific hardware implementation is still far from being certain, in fact the race between the most promising platforms such as superconducting qubits, bosonic codes, cold atoms, trapped ions, optical computing as well as spin qubits has recently intensified. If one also includes the most mature applications of quantum communication technologies, secure quantum key distribution and quantum random number generators, as part of a quantum information technology ecosystem, we are confronted with a plethora of different materials, concepts, and also operation frequencies. While superconducting qubits, bosonic codes and spin qubits work in the regime of approximately 5 GHz and are controlled by electrical fields, trapped ions, cold atoms, and optical quantum computing operate with light in the infrared or visible range. Consequently, a quantum frequency converter or microwave-optic transducer is required to interface the different frequency domains or establish a long-range network connection with suitable telecom fibers. In fact, the combination of different frequency regimes is also an essential part in our classical modern communication network, where computations are performed in electrical circuits and the information exchange over longer distances happens via optical fibers. However, the specific challenges specific to building a quantum computer, also apply to the development of such a quantum frequency transducer: 1) As we deal with single excitations as the carrier of information, i.e. the smallest possible quantity, the signal can easily be corrupted by other noise sources which needs to be avoided by all means. This is also the reason why microwave quantum computers operate at temperature environments close to zero temperature (< 0.1 Kelvin) to avoid corruption by thermal noise. 2) The frequency interface generally needs to preserve the phase of the signal as an essential part of the quantum state. And 3) Quantum signals cannot be copied which would be a typical strategy to account for errors in classical computers. And finally, there is a challenge specific to microwave-optic transducers: While quantum computers are operating in one specific frequency domain, microwave-optic transducers combine microwave and optical fields in one device. This results in the particular challenge that high-energy optical radiation, which is usually well-shielded from superconducting microwave quantum processors, are now an essential part of the device. The concomitant optical radiation in the operating transducer will inevitably have a detrimental effect on the superconducting microwave components. Together with the requirement of minimal background noise for quantum-limited operation as described above, v heating from the absorption of optical photons within the same device where single microwave excitations are processed forms a formidable challenge. This thesis aims to address this challenge by developing microwave-optic transducers where the impact of optical absorption on superconducting circuits in general and superconducting qubits specifically can be mitigated. In our first approach, we developed a compact device with optimized interaction strengths between the different frequency domains. This minimizes the optical powers used for transducer operation and thus the optical absorption heating. This work was - to the best of our knowledge - the first comprehensive noise study, in an integrated microwave-optic transducer. Unfortunately, we saw that the optical absorption heating added noise way above a single excitation. Consequently, a potential quantum signal would have been buried in the noise, added by the transduction. Building on this insight, we utilized a three-dimensional microwave-optic transducer instead of an integrated device. The larger heat capacity of the macroscopic device with a size of a few millimeters can absorb a larger fraction of the optical heating before it increases the temperature of the device. This allowed us to interface the transducer directly with a superconducting qubit to readout the qubit state in a novel all-optical manner. We showed that the microwave-optic transducer can be operated in a regime in which optical fields don’t harm the sensitive qubit. This is an important prerequisite for the operation of microwave-optic transducers in conjunction with microwave quantum processors and brings the integration and seamless orchestration of different frequency components in a quantum network a step closer. }, author = {Arnold, Georg M}, issn = {2663-337X}, pages = {135}, publisher = {Institute of Science and Technology Austria}, title = {{Microwave-optic interconnects for superconducting circuits}}, doi = {10.15479/at:ista:18871}, year = {2025}, } @phdthesis{19745, abstract = {Cell migration is a crucial process in animal development and maintenance. It is incredibly heterogeneous, with different cell types utilizing fundamentally distinct migration strategies. The strategies also depend on the cellular microenvironment, where cells can switch between migration modes as they encounter new environmental cues. In this thesis, we investigated how dendritic cells adapt their migration strategy when encountering geometrically, mechanically and chemically distinct environments. When dendritic cells are embedded in a homogeneous fibrous network, they migrate in a fast and directional amoeboid manner. In this migration strategy, extracellular proteolysis and integrin-mediated adhesions are dispensable. Instead, the cells use topography of the environment to propel their cell body forward. To migrate efficiently in the maze of different pore sizes, they position the nucleus ahead of the microtubule organizing center (MTOC) and use it to gauge the pores to identify the path of least resistance. Our aim was to identify whether dendritic cells adapt their migration strategy when encountering asymmetrical transitions into much denser environments with limited choice of large pores. In such invasive transitions it is unclear if the cells can cross tight pores without the use of adhesions and extracellular proteolysis and whether they maintain the nucleus in the cell front. Using various cell migration assays such as fibrous 3D collagen gels, geometrically defined microchannels with constrictions and simplistic under agarose migration assay, we provide a comprehensive characterization of invasive migration of dendritic cells. We show that during invasion the cells stall and stretch, reflecting the difficulty to translocate the bulky cell body into the dense environment. In collagen gels, we show that dendritic cells can invade without proteolysis and adhesions. Instead, they utilize contractility, which can lead to largescale collagen compressions. During invasion, the nucleus stalls at tight constrictions, leading to a transient organelle reorientation. To resolve the stalling, upregulated rear contractility is required. This contractile force is simultaneously necessary for reverting the nucleus back to the cell front after invasion and maintaining this positioning during permissive migration. A functional role of the reorientation was uncovered in the first collaboration project. A prominent central actin pool was identified around the MTOC, especially pronounced in dense and compressive environments. The actin pool was shown to generate pushing forces to dilate the space for cell translocation. These forces are only necessary in non-permissive environments, where the nucleus reorients to the cell rear, allowing the actin pool to generate space. In permissive environments where space generation is dispensable, the MTOC is located behind the nucleus and the actin cloud has reduced intensity, allowing more actin to be incorporated into the lamellipodium, speeding up migration. In the second collaboration project, we investigated the effects of distinct chemical environments on dendritic cell migration. The strikingly persistent migration of these cells was explained by their ability to modulate and even self-generate chemokine gradients. This allows the cells to migrate faster and more persistent in uniform chemokine fields compared to imposed chemokine gradients. The chemokine receptor CCR7 was identified as a crucial player in this process, both sensing the signal and internalizing the chemokine to create a sink.}, author = {Canigova, Nikola}, isbn = {978-3-99078-058-9}, issn = {2663-337X}, pages = {133}, publisher = {Institute of Science and Technology Austria}, title = {{Adaptive strategies of dendritic cell migration in response to environmental cues}}, doi = {10.15479/AT-ISTA-19745}, year = {2025}, } @phdthesis{19271, abstract = {The medial habenula (MHb) is implicated in regulating emotional responses to aversive events. Studies in zebrafish have identified a remarkable morphological left-right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian MHb)-to-interpeduncular nucleus (IPN) pathway and its left-side specific role in modulating fear responses. However, there is little evidence for structural or functional lateralization in the mammalian MHb-IPN pathway. Here, I investigated the synaptic properties of the left and right MHb afferents to the IPN in mice and addressed whether these synaptic connections selectively influence the expression of conditioned fear in mice. My findings reveal that each individual IPN neuron receives inputs from both left and right MHb. Electrophysiological recordings from the same postsynaptic IPN neurons demonstrate that the left MHb-originating synapses exhibit lower release probability and higher 𝛾-aminobutyric acid type B receptor (GABABR)-mediated potentiation compared to the right MHb-originating synapses. Interestingly, chemogenetic inhibition of cholinergic neurons in the left but not the right MHb significantly attenuated cue-dependent fear recall. Furthermore, conditional deletion of GABABR in the left MHb interfered with the recall of cued fear memory, whereas that in the right MHb neurons spared fear memory expression. Collectively, I demonstrate a functional asymmetry of the MHb in mice, revealing a predominant role for GABABR-mediated signaling in the left MHb-IPN pathway in the modulation of fear memories. These findings suggest that lateralized pathways could represent a fundamental principle in the neural regulation of emotion across species.}, author = {Önal, Hüseyin C}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula}}, doi = {10.15479/AT-ISTA-19271}, year = {2025}, } @phdthesis{19431, abstract = {Gene expression is crucial for cell differentiation, development and survival of organisms. It consists of several steps, starting with transcription that is mediated by RNA polymerases. These are protein machineries transcribing and producing different types of RNAs. Although, the individual steps of transcription by RNA polymerase II (Pol II) as well as the structure of Pol II has been extensively studied, surprisingly, there is still little known about its regulation and assembly in cytoplasm. Among the proteins that are important in biogenesis of Pol II are RNA polymerase II associating proteins (RPAP) and small GPN-loop GTPases (GPN). Both of these protein groups were shown to take essential part in assembly of Pol II. The aim of this project was to deepen our knowledge in regulation of Pol II in the cytoplasm as well as the proteins involved in this process. Techniques of structural biology, biochemistry and cell biology were employed to study and characterize cytoplasmic Pol II and its interacting partners. This study shows for the first time the structure of cytoplasmic Pol II at high resolution. The structure also reveals proteins interacting with Pol II in cytoplasm, namely GDOWN1, RPAP2. Comparing the structure of cytoplasmic Pol II with transcribing Pol II revealed striking difference in clamp region that is not in closed state. Furthermore, GDOWN1 and RPAP2 make steric clashes with various transcription factors bound to Pol II during different stages of transcription. Even though GPN1 and GPN3 proteins were not resolved in the cytoplasmic Pol II structure, they are part of the complex and their interaction with Pol II was confirmed in vitro. RPAP2 stabilizes these proteins on Pol II and several experiments suggest that they interact with the clamp region. In addition, GDOWN1, RPAP2 and GPNs might keep clamp in open or partially open state. Based on these results I propose a novel model of regulation of Pol II in cytoplasm. GDOWN1, RPAP2, GPN1 and GPN3 bind to Pol II in cytoplasm and doing so they can prevent pre-mature binding of DNA or RNA and different transcription factors to Pol II in cytoplasm or before engaging in transcription nucleus. This research contributes to the current knowledge of molecular mechanisms of Pol II regulation in cytoplasm.}, author = {Hlavata, Annamaria}, isbn = {978-3-99078-055-8}, issn = {2663-337X}, pages = {83}, publisher = {Institute of Science and Technology Austria}, title = {{Regulation of Cytoplasmic RNA Polymerase II}}, doi = {10.15479/10.15479/AT-ISTA-19431}, year = {2025}, } @phdthesis{19302, abstract = {Social interaction networks of insect colonies facilitate efficient information exchange and demonstrate adaptive changes to mitigate disease transmission. While circadian rhythms influence individual behaviour, their role in shaping colony-level defences against pathogens remains unexplored. Here, we investigate whether social networks of the black garden ant, Lasius niger, exhibit circadian rhythms and how these rhythms influence disease vulnerability when colonies are exposed to a pathogen during the day or the night. We first establish baseline daily variations in activity and network dynamics in pathogen-free colonies, revealing constitutive daily fluctuations in disease susceptibility. Subsequently, we examine pathogen-induced changes in sanitary care and network dynamics by exposing foragers to a natural pathogen (Metarhizium brunneum) during either the day or the night. Individual pathogen loads were measured after a nine-hour post-exposure period to evaluate transmission outcomes. Our results demonstrate that diurnal ant colonies maintain robust circadian patterns in network properties while flexibly adapting to pathogen exposure. Ants upregulate sanitary care irrespective of exposure timing, prioritising the protection of the valuable colony centre consisting of nurses and the queen. These findings underscore the robustness and adaptability of ant colonies in balancing circadian rhythms with effective social immune responses.}, author = {Sartoris, Linda}, issn = {2663-337X}, pages = {85}, publisher = {Institute of Science and Technology Austria}, title = {{The effect of circadian rhythm on organisational immunity of ant colonies}}, doi = {10.15479/AT-ISTA-19302}, year = {2025}, }