@article{14980,
abstract = {Precision sensing and manipulation of milligram-scale mechanical oscillators has attracted growing interest in the fields of table-top explorations of gravity and tests of quantum mechanics at macroscopic scales. Torsional oscillators present an opportunity in this regard due to their remarked isolation from environmental noise. For torsional motion, an effective employment of optical cavities to enhance optomechanical interactions—as already established for linear oscillators—so far faced certain challenges. Here, we propose a concept for sensing and manipulating torsional motion, where exclusively the torsional rotations of a pendulum are mapped onto the path length of a single two-mirror optical cavity. The concept inherently alleviates many limitations of previous approaches. A proof-of-principle experiment is conducted with a rigidly controlled pendulum to explore the sensing aspects of the concept and to identify practical limitations in a potential state-of-the art setup. Based on this study, we anticipate development of precision torque sensors utilizing torsional pendulums that can support sensitivities below 10−19Nm/√Hz, while the motion of the pendulums are dominated by quantum radiation pressure noise at sub-microwatts of incoming laser power. These developments will provide horizons for experiments at the interface of quantum mechanics and gravity.},
author = {Agafonova, Sofya and Mishra, Umang and Diorico, Fritz R and Hosten, Onur},
issn = {2643-1564},
journal = {Physical Review Research},
number = {1},
publisher = {American Physical Society},
title = {{Zigzag optical cavity for sensing and controlling torsional motion}},
doi = {10.1103/physrevresearch.6.013141},
volume = {6},
year = {2024},
}
@article{14802,
abstract = {Frequency-stable lasers form the back bone of precision measurements in science and technology. Such lasers typically attain their stability through frequency locking to reference cavities. State-of-the-art locking performances to date had been achieved using frequency modulation based methods, complemented with active drift cancellation systems. We demonstrate an all passive, modulation-free laser-cavity locking technique (squash locking) that utilizes changes in spatial beam ellipticity for error signal generation, and a coherent polarization post-selection for noise resilience. By comparing two identically built proof-of-principle systems, we show a frequency locking instability of 5×10−7 relative to the cavity linewidth at 10 s averaging. The results surpass the demonstrated performances of methods engineered over the last five decades, potentially enabling an advancement in the precision control of lasers, while creating avenues for bridging the performance gaps between industrial grade lasers with scientific ones due to the afforded simplicity and scalability.},
author = {Diorico, Fritz R and Zhutov, Artem and Hosten, Onur},
issn = {2334-2536},
journal = {Optica},
keywords = {Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials},
number = {1},
pages = {26--31},
publisher = {Optica Publishing Group},
title = {{Laser-cavity locking utilizing beam ellipticity: accessing the 10−7 instability scale relative to cavity linewidth}},
doi = {10.1364/optica.507451},
volume = {11},
year = {2024},
}
@phdthesis{17225,
abstract = {This thesis describes the development of an atom interferometer designed to exploit the
advantages of utilizing quantum entanglement for enhanced precision measurements beyond
the standard quantum limit. While the project remains ongoing, significant progress has been
made.
A key contribution of this work is the development of Quantrol, an experimental control
system leveraging the ARTIQ framework. This software enables precise timing and control
without requiring prior knowledge of ARTIQ’s implementation details or coding experience.
The interface offers user friendly visual comprehension of the experimental sequence and
extended capabilities, allowing researchers to scan variables with a simple click of a mouse.
The main proposed project is to implement atom interferometric sequence with squeezed input
states inside of a dipole trap generated by a high finesse cavity. The presence of the dipole
trap allows one dimensional atomic cloud split while maintaining relatively strong confinement
in other directions.
We are currently able to trap and cool 87Rb atoms to few micro kelvin temperatures, load
them into the dipole trap and state prepare them to be used for squeezing and interferometric
sequence.},
author = {Li, Vyacheslav},
issn = {2663-337X},
pages = {79},
publisher = {Institute of Science and Technology Austria},
title = {{Towards a quantum entanglement enhanced atom interferomter}},
doi = {10.15479/at:ista:17225},
year = {2024},
}
@unpublished{19550,
abstract = {We introduce a multi-band BCS free energy functional and prove that for a
multi-band superconductor the effect of inter-band coupling can only increase
the critical temperature, irrespective of its attractive or repulsive nature
and its strength. Further, for weak coupling and weaker inter-band coupling, we
prove that the dependence of the increase in critical temperature on the
inter-band coupling is (1) linear, if there are two or more equally strongly
superconducting bands, or (2) quadratic, if there is only one dominating band.},
author = {Henheik, Sven Joscha and Langmann, Edwin and Lauritsen, Asbjørn Bækgaard},
booktitle = {arXiv},
title = {{Multi-band superconductors have enhanced critical temperatures}},
doi = {10.48550/arXiv.2409.17297},
year = {2024},
}
@article{15169,
abstract = {Interpretation of extracellular recordings can be challenging due to the long range of electric field. This challenge can be mitigated by estimating the current source density (CSD). Here we introduce kCSD-python, an open Python package implementing Kernel Current Source Density (kCSD) method and related tools to facilitate CSD analysis of experimental data and the interpretation of results. We show how to counter the limitations imposed by noise and assumptions in the method itself. kCSD-python allows CSD estimation for an arbitrary distribution of electrodes in 1D, 2D, and 3D, assuming distributions of sources in tissue, a slice, or in a single cell, and includes a range of diagnostic aids. We demonstrate its features in a Jupyter Notebook tutorial which illustrates a typical analytical workflow and main functionalities useful in validating analysis results.},
author = {Chintaluri, Chaitanya and Bejtka, Marta and Sredniawa, Wladyslaw and Czerwinski, Michal and Dzik, Jakub M. and Jedrzejewska-Szmek, Joanna and Wojciki, Daniel K.},
issn = {1553-7358},
journal = {PLoS Computational Biology},
number = {3},
publisher = {Public Library of Science},
title = {{kCSD-python, reliable current source density estimation with quality control}},
doi = {10.1371/journal.pcbi.1011941},
volume = {20},
year = {2024},
}
@inproceedings{17147,
abstract = {Efficient utilization of large-scale biobank data is crucial for inferring the genetic basis of disease and predicting health outcomes from the DNA. Yet we lack efficient, accurate methods that scale to data where electronic health records are linked to whole genome sequence information. To address this issue, our paper develops a new algorithmic paradigm based on Approximate Message Passing (AMP), which is specifically tailored for genomic prediction and association testing. Our method yields comparable out-of-sample prediction accuracy to the state of the art on UK Biobank traits, whilst dramatically improving computational complexity, with a 8x-speed up in the run time. In addition, AMP theory provides a joint association testing framework, which outperforms the currently used REGENIE method, in roughly a third of the compute time. This first, truly large-scale application of the AMP framework lays the foundations for a far wider range of statistical analyses for hundreds of millions of variables measured on millions of people.},
author = {Depope, Al and Mondelli, Marco and Robinson, Matthew Richard},
booktitle = {2024 IEEE International Conference on Acoustics, Speech, and Signal Processing},
isbn = {9798350344851},
issn = {1520-6149},
location = {Seoul, Korea},
pages = {13151--13155},
publisher = {IEEE},
title = {{Inference of genetic effects via approximate message passing}},
doi = {10.1109/ICASSP48485.2024.10447198},
year = {2024},
}
@article{15182,
abstract = {Thermoelectric materials convert heat into electricity, with a broad range of applications near room temperature (RT). However, the library of RT high-performance materials is limited. Traditional high-temperature synthetic methods constrain the range of materials achievable, hindering the ability to surpass crystal structure limitations and engineer defects. Here, a solution-based synthetic approach is introduced, enabling RT synthesis of powders and exploration of densification at lower temperatures to influence the material's microstructure. The approach is exemplified by Ag2Se, an n-type alternative to bismuth telluride. It is demonstrated that the concentration of Ag interstitials, grain boundaries, and dislocations are directly correlated to the sintering temperature, and achieve a figure of merit of 1.1 from RT to 100 °C after optimization. Moreover, insights into and resolve Ag2Se's challenges are provided, including stoichiometry issues leading to irreproducible performances. This work highlights the potential of RT solution synthesis in expanding the repertoire of high-performance thermoelectric materials for practical applications.},
author = {Kleinhanns, Tobias and Milillo, Francesco and Calcabrini, Mariano and Fiedler, Christine and Horta, Sharona and Balazs, Daniel and Strumolo, Marissa J. and Hasler, Roger and Llorca, Jordi and Tkadletz, Michael and Brutchey, Richard L. and Ibáñez, Maria},
issn = {1614-6840},
journal = {Advanced Energy Materials},
number = {22},
publisher = {Wiley},
title = {{A route to high thermoelectric performance: Solution‐based control of microstructure and composition in Ag2Se}},
doi = {10.1002/aenm.202400408},
volume = {14},
year = {2024},
}
@inproceedings{18557,
abstract = {Broadcast and Consensus are most fundamental tasks in distributed computing. These tasks are particularly challenging in dynamic networks where communication across the network links may be unreliable, e.g., due to mobility or failures. Over the last years, researchers have derived several impossibility results and high time complexity lower bounds for these tasks. Specifically for the setting where in each round of communication the adversary is allowed to choose one rooted tree along which the information is disseminated, there is a lower as well as an upper bound that is linear in the number n of nodes for Broadcast and for n ≥ 3 the adversary can guarantee that Consensus never happens. This setting is called the oblivious message adversary for rooted trees. Also note that if the adversary is allowed to choose a graph that does not contain a rooted tree, then it can guarantee that Broadcast and Consensus will never happen. However, such deterministic adversarial models may be overly pessimistic, as many processes in real-world settings are stochastic in nature rather than worst-case. This paper studies Broadcast on stochastic dynamic networks and shows that the situation is very different to the deterministic case. In particular, we show that if information dissemination occurs along random rooted trees and directed Erdős–Rényi graphs, Broadcast completes in O(log n) rounds of communication with high probability. The fundamental insight in our analysis is that key variables are mutually independent. We then study two adversarial models, (a) one with Byzantine nodes and (b) one where an adversary controls the edges. (a) Our techniques without Byzantine nodes are general enough so that they can be extended to Byzantine nodes. (b) In the spirit of smoothed analysis, we introduce the notion of randomized oblivious message adversary, where in each round, an adversary picks k ≤ 2n/3 edges to appear in the communication network, and then a graph (e.g. rooted tree or directed Erdős–Rényi graph) is chosen uniformly at random among the set of all such graphs that include these edges. We show that Broadcast completes in a finite number of rounds, which is, e.g., O(k+log n) rounds in rooted trees. We then extend these results to All-to-All Broadcast, and Consensus, and give lower bounds that show that most of our upper bounds are tight.},
author = {El-Hayek, Antoine and Henzinger, Monika H and Schmid, Stefan},
booktitle = {38th International Symposium on Distributed Computing},
isbn = {9783959773522},
issn = {1868-8969},
location = {Madrid, Spain},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Broadcast and Consensus in stochastic dynamic networks with Byzantine nodes and adversarial edges}},
doi = {10.4230/LIPIcs.DISC.2024.21},
volume = {319},
year = {2024},
}
@phdthesis{17119,
abstract = {Genomes are shaped by natural selection at the level of the organism, as genomic variants that
have a beneficial effect on the viability or fecundity of their carriers are on average expected
to be passed on to more offspring than less beneficial alleles. However, selection also favors
genomic variants that drive their own transmission to the next generation above the mendelian
expectation of 50 percent in heterozygotes, even if these self-promoting variants are less
beneficial to the organism than other variants at the same locus. Such variants, called meiotic
drivers, are found in diverse taxa, and often impose fitness costs on their host organisms. As
meiotic drivers often require multiple genes and sequences for transmission ratio distortion,
they are often found in regions of low recombination, such as inversions, which prevent their
recombination with the non-driving homologous regions. Reduced recombination rates are
expected to lead to the accumulation of deleterious mutations, which may affect hundreds
of genes trapped in the inversions of meiotic drivers. Although the observed fitness costs of
self-promoting haplotypes are thought to possibly reflect sequence degeneration, no study has
systematically investigated the level of degeneration on a meiotic driver. Further, the low
rates of recombination between driving and non-driving haplotypes have limited the power of
traditional genetic studies in uncovering the gene content of meiotic drivers, and made the
the identification of the genes causing transmission ratio distortion difficult.
After an introduction to meiotic drivers in Chapter 1, this thesis presents three studies that
make use of next generation sequencing data to characterize the sequence and expression
evolution of genes on the t-haplotype, a large and ancient meiotic driver in house mice that is
transmitted to up to 100% of the offspring in males heterozygous for it. Chapter 2 presents
a comprehensive assessment of the t-haplotype’s sequence evolution, which shows signs of
sequence degeneration counteracted by occasional recombination with the non-driving homolog
over large parts of the meiotic driver, proposing an explanation for its long-term survival.
Chapter 3 investigates the sequence and expression evolution of genes on the t-haplotype,
and finds widespread expression and copy number changes and signs of less efficient purifying
selection compared to the genes on the non-driving homolog. Further, this chapter finds
candidates for involvment in drive: two positively selected genes on the t-haplotype, and
the discovery of a t-specific gene duplicate, which was gained from another chromosome,
and which acquired novel sequence and testis-specific expression on the t-haplotype. Finally,
Chapter 4 provides unprecedented insights into the gene expression landscape in testes of
t-carrier mice, using single nucleus sequencing. Cell-resolved RNA-sequencing allows the
comparison of expression in spermatids carrying or not carrying the t-haplotype as well as the
timing of t-haplotype-induced expression changes along spermatogenesis. This study shows
the timing of previously found drive-associated genes, and uncovers novel candidate genes and
biological processes that may underlie the complex biology of transmission ratio distortion of
the t-haplotype. Chapter 5 synthesizes the findings of the three studies, and discusses them in
the context of the current state of meiotic drive research.},
author = {Kelemen, Réka K},
isbn = {978-3-99078-039-8},
issn = {2663-337X},
keywords = {meiotic driver, neofunctionalization, single nucleus sequencing},
pages = {105},
publisher = {Institute of Science and Technology Austria},
title = {{Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver}},
doi = {10.15479/at:ista:17119},
year = {2024},
}
@phdthesis{18477,
abstract = {ADAR1 is broadly expressed across various tissues and is vital in regulating pathways
associated with innate immune responses. ADAR1 marks double-stranded RNA as "self"
through its A-to-I editing activity, effectively repressing autoimmunity and maintaining
immune tolerance. This editing process has been detected at millions of sites across the
human genome. However, the mechanism underlying ADAR1's substrate selectivity
properties remains largely unclear, with much of the current knowledge derived from
comparisons to its more extensively studied homolog, ADAR2. By studying ADAR1 in complex
with its RNA substrates and applying a combination of biochemical techniques and structural
studies using CryoEM, we aim to gain a more comprehensive understanding of the substrate
selectivity characteristics of ADAR1.
In this thesis, the purification protocol for ADAR1 was successfully optimized, resulting in the
first report in the literature to achieve high protein purity and activity. This advancement
enabled the investigation of complex formation between ADAR1 and various RNA substrates,
leading to the identification of optimal conditions for preparing the cryoEM sample. However,
despite comprehensive optimization of the cryo-EM conditions, the resulting data lacked the
desired quality, highlighting the need for similar rigorous optimization of the RNA substrates
to facilitate structural studies of the ADAR1-RNA complex. The study was complemented by
AlphaFold predictions, which provided some insights into this mechanism.
Moreover, during this project I established a collaboration with a research group focused on
studying ADAR homologs. Notably ADAR homologs were identified in bivalve species, and it
was further demonstrated that ADAR and its A-to-I editing activity are upregulated in Pacific
oysters during infections with Ostreid herpesvirus-1—a highly infectious virus that leads to
significant losses in oyster populations globally. I successfully purified oyster ADAR and
prepared in vitro edited RNA for nanopore sequencing—a direct sequencing technology
capable of detecting modified nucleotides without the need for reverse transcription. The
collaborators initiated optimization of this nanopore-based approach. However, current
technological limitations still constrain the reliable detection of modified nucleotides.
The project also examined the impact of RNA editing on RNA binding and filament formation
by MDA5, a key cytosolic dsRNA sensor that triggers an interferon response. A primary target
of ADAR1's editing activity is RNA derived from repetitive elements present in the genome,
particularly Alu elements forming double-stranded RNA. When unedited, these RNA
sequences are recognized by MDA5. However, the mechanisms by which MDA5 interacts with
Alu RNAs, as well as the role of A-to-I editing in influencing this binding, are still not well
understood.
The interaction between MDA5 and Alu elements, was successfully established. This was
achieved through the testing of different RNA variants and the evaluation of filament
formation using binding techniques and electron microscopy imaging. This groundwork has
set the conditions for further evaluation using CryoEM. Furthermore, the effects of A-to-I
editing on the binding properties of MDA5 with Alu RNA were investigated. Given the recent
research that has provided new insights into MDA5's interaction with dsRNA, it is essential to
revise the experimental setup to integrate these findings before moving forward with the
CryoEM sample analysis.},
author = {Kaczmarek, Beata M},
isbn = {978-3-99078-045-9},
issn = {2663-337X},
pages = {124},
publisher = {Institute of Science and Technology Austria},
title = {{Biochemical and structural insights into ADAR1 RNA editing}},
doi = {10.15479/at:ista:18477},
year = {2024},
}
@phdthesis{15352,
abstract = {Epilepsy affects about 50 to 65 million people globally. It summarizes a spectrum of neurological
disorders that have in common a hyperactivity of the neuronal network resulting in seizures. A common
assumption is that an imbalance between neuronal excitation and inhibition is a key mechanism in
seizure generation and epileptogeneisis. In at least one-third of the patients, current therapies have
proven unsuccessful in treating seizure progression. One potential reason could be that the therapies
only focus on neurons. Recent studies suggest that neuronal hyperactivity causes a microglial
response, which reinstates brain homeostasis. Additionally, interactions between microglia and neurons
have been shown to inhibit neuronal firing and dampen seizure activity. However, the exact relationship
between microglia and seizure progression in epilepsy is yet to be elucidated. A main bottleneck is that
several studies investigate microglia dynamics in ex vivo slice models, which can severely affect the
microglia dynamics due to their rapid response to environmental changes. On the other hand, in vivo
studies focus mostly on behavior characterization of the epileptic seizure phenotype and their long-term
consequences on microglia activity leaving out the direct consequences of acute seizure activity on
microglia dynamics.
Here, we perform a pilot study to combine electroencephalography (EEG) and in vivo live imaging to
directly monitor and correlate the onset of seizure activity with microglia response. To induce seizures,
we take advantage of the kainic acid (KA) model, which represents similar neuropathological and
electroencephalographic features seen in human patients with temporal lobe epilepsy (TLE). After
confirmation of induction of the seizure and microglia activity in the hippocampus as a focal point, we
investigated whether these changes also reached the primary visual cortex (V1) as a secondary
generalized seizure activity. Indeed, we found that microglia changed their morphology at high doses
of KA in the V1. Next, we optimized each of the two methodological components: for the EEG recording,
our initial attempts under the microscope suffered from extensive electrical noise, which overlaid the
actual signal. Thus, we built a customized Faraday-cage and confirmed that the signal-to-noise ratio
was sufficiently reduced to be able to record brain oscillatory activity. For the in vivo live imaging of
microglia, we had to optimize the imaging parameters, so that we would be able to detect microglial
processes in a sufficient resolution to track their process changes. Finally, we combined both
methodologies with the KA model. We confirmed that KA induced seizure activity and found first
indication that those correlate with microglia volume changes.
Overall, we have developed a first methodological approach, which allows the analysis of the acute
effects of seizure onset on microglia. Future studies will have to continue to optimize the drift during
imaging recording and the post-image analysis. },
author = {Murmann, Julie Stefanie},
issn = {2791-4585},
pages = {54},
publisher = {Institute of Science and Technology Austria},
title = {{Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording}},
doi = {10.15479/at:ista:15352},
year = {2024},
}
@article{14843,
abstract = {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.},
author = {Chen, JingJing and Kaufmann, Walter and Chen, Chong and Arai, Itaru and Kim, Olena and Shigemoto, Ryuichi and Jonas, Peter M},
issn = {1097-4199},
journal = {Neuron},
number = {5},
pages = {755--771.e9},
publisher = {Elsevier},
title = {{Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse}},
doi = {10.1016/j.neuron.2023.12.002},
volume = {112},
year = {2024},
}
@phdthesis{14821,
abstract = {The hippocampus is central to memory formation, storage and retrieval over many
timescales. Neurons in this brain area are highly selective to spatial position as well as to many
other variables of the environment. It is believed that the selectivity patterns of hippocampal
neurons reflect the structure of tasks an animal performs. However, especially at timescales
longer than a few minutes or hours it is not fully known how these representations evolve, nor
how they map to behaviour in the process. In this thesis, I monitored the evolution of
hippocampal representations in a novel spatial-associative memory task for rats. Reward
locations were associated with global sensory cues (i.e. context); animals had to remember the
associations and dig for food in those locations only. I used in vivo electrophysiology to record
the activity of the hippocampus dorsal CA1 neurons during the learning period of a few days.
I report here a novel and simple method to classify behaviour performance to account
for individual variability in learning speed and spurious performance unrelated to true task rule
learning. Using this classification I was then able to investigate neural responses on different
stages of learning matched across animals. On the first day of learning, I observed a fast
formation of single-cell selectivity to task variables which remained stable over days. I also
observed that reward tuning was not a single process but dependent on task-related cognitive
load. At the population level, a linear decoding approach revealed a hierarchy in the
representation of task variables that changed with learning. In the high-dimensional space of
population activity, the representation of contexts was specific to each position in the maze, and
could thus be better decoded if the position was known. The decoding of position did not improve
with knowledge of other variables. As learning progressed, the hippocampal code underwent a
reorganisation of high-variance directions in population activity, identified by principal
component analysis. I found that dominant dimensions started carrying increasing amounts of
information about task context specifically at those positions where it mattered for task
performance. When I contrasted this with variables less relevant to task performance (e.g.
movement direction), I did not observe differences in decoding quality over positions nor a
reduction of dimensionality with learning.
Overall, the largest changes in CA1 neural response with task learning happened in a
matter of a few trials; over days, changes undetectable in single-cell statistics were responsible
for re-structuring the hierarchy of neural representations at the population level; these changes
were task-specific and reflected different stages of learning. This indicates that complex task
learning may involve different magnitudes of response modulation in CA1, which happen at
specific time scales linked to behaviour.},
author = {Chiossi, Heloisa},
issn = {2663-337X},
pages = {89},
publisher = {Institute of Science and Technology Austria},
title = {{Adaptive hierarchical representations in the hippocampus}},
doi = {10.15479/at:ista:14821},
year = {2024},
}
@phdthesis{15101,
abstract = {The coupling between presynaptic Ca2+ channels and release sensors is a key factor that
determines speed and efficacy of synapse transmission. At some excitatory synapses,
channel–sensor coupling becomes tighter during development, and tightening is often
associated with a switch in the reliance on different Ca2+ channel subtypes. However, the
coupling topography at many synapses remains unknown, and it is unclear how it changes
during development. To address this question, we analyzed the coupling configuration at the
cerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,
combining biophysical analysis, structural analysis, and modeling.
Quantal analysis of BC–PC indicated that release probability decreased, while the
number of functional sites increased during development. Although transmitter release
persistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects
of the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased
during development, indicative of tightening of source-sensor coupling. Furthermore,
presynaptic action potentials became shorter during development, suggesting reduced
efficacy of Ca2+ channel activation.
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. The number of functional release sites correlated better with the AZ
number early in development, but match better with the Ca2+ channel cluster number at later
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.},
author = {Chen, JingJing},
issn = {2663-337X},
pages = {84},
publisher = {Institute of Science and Technology Austria},
title = {{Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse}},
doi = {10.15479/at:ista:15101},
year = {2024},
}
@phdthesis{18471,
abstract = {Spatial omics technologies are enriching our understanding of complex biological samples, by
allowing us to study their molecular composition while preserving the spatial relationships
between molecules in their native context. As the field continues to advance, there are
technical challenges that need to be addressed in order to take full advantage of the spatial
capabilities of these methods. In this work, I present two technical developments that I
established for multiplexed error robust FISH (MERFISH) throughout my PhD: (1) pushing the
spatial resolution limits to the nanoscale, and (2) adding rich tissue context to the mouse brain
transcriptome. To achieve nanoscale resolution with MERFISH in cultured cells, I combined it
with stimulated emission depletion (STED) and expansion microscopy (ExM) to achieve a
spatial resolution as low as ~20 nm, and explored the compatibility of MERFISH with singlemolecule localization microscopy (SMLM) techniques. To visualize targeted mRNAs in mouse
brain tissue, I applied the comprehensive analysis of tissues across scales (CATS) toolbox, which
provides an unbiased morphological readout by labeling the extracellular domain. I
successfully established this method, which we call CATS-MERFISH-ExM, to work with thick
mouse brain slices, being able to extract transcriptomics information with 3D tissue context.
CATS-MERFISH-ExM enabled us to identify cell types and further visualize the subcellular
distribution of transcripts in mouse brain tissue, shedding light on the neuropil-specific
transcriptome. This method provides integrated information on cellular structure and
transcriptomes in situ, and could potentially be applied with other modalities, opening new
avenues for scientific discovery. },
author = {Agudelo Duenas, Nathalie},
isbn = {978-3-99078-044-2},
issn = {2663-337X},
pages = {97},
publisher = {Institute of Science and Technology Austria},
title = {{Visualizing the neuronal transcriptional landscape with tissue context}},
doi = {10.15479/at:ista:18471},
year = {2024},
}
@phdthesis{18574,
abstract = {Biological vision is unlike a camera; rather than transmitting light information faithfully, early
visual circuits process the visual scene to convey only the relevant information in an efficient
manner. Consequentially, the nature of this visual processing then depends on what is the
relevant information in a scene and on the notion of efficiency. In this work, I study how visual
processing is modulated by two different variations in the visual scene. First, I discovered that
in the mouse (Mus musculus) retina, Retinal Ganglion Cells in the upper and lower visual
field have differences in the center surround structure of their receptive fields. Comparison
with models of efficient coding show that this adaptation likely evolved to cope with the
brightness gradient from the sky to the ground that is pervasive in natural scenes. In the
second project, I study how the downstream neurons in the Superior Colliculus dynamically
change their temporal selectivity depending on the ambient luminance and behavioral state.
As the scene gets darker or when the animal is is less aroused, the neuronal responses get
laggier, while still maintaining their relative timing with respect to the population. Overall, this
work emphasises the need to understand visual processing in the context of specific demands
of the animal in its the environment. The adaptive changes in the visual system, from the
retinal ganglion cells to the superior colliculus, highlight the intricate ways in which biological
vision optimizes the processing of visual information.
},
author = {Gupta, Divyansh},
isbn = {978-3-99078-050-3},
issn = {2663-337X},
pages = {86},
publisher = {Institute of Science and Technology Austria},
title = {{Visual adaptations to natural statistics}},
doi = {10.15479/at:ista:18574},
year = {2024},
}
@article{15323,
abstract = {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.},
author = {Vercellino, Irene and Sazanov, Leonid A},
issn = {1545-9985},
journal = {Nature Structural and Molecular Biology},
pages = {1061--1071},
publisher = {Springer Nature},
title = {{SCAF1 drives the compositional diversity of mammalian respirasomes}},
doi = {10.1038/s41594-024-01255-0},
volume = {31},
year = {2024},
}
@phdthesis{18531,
abstract = {Sex chromosomes and autosomes exhibit very different evolutionary dynamics.
The Y chromosome usually degenerates, leaving many X-linked loci hemizygous in
males. Since recessive X-linked mutations are always exposed to selection in males,
selection is more efficient on the X chromosome than on autosomes on recessive
mutations, leading to faster adaptation on the X chromosome than other genomic
regions, if beneficial mutations are on average recessive (known as the Faster-X
effect). In the presence of the functional, but non-recombining gametolog on the Y (as
is often the case in young non-recombining regions), recessive mutations are
sheltered from selection on the X chromosome. We model this scenario and show that
the efficiency of selection is reduced on diploid X loci due to sheltering by the Y
chromosome. Reduced efficiency of selection leads to slower adaptation and
increased accumulation of deleterious mutations (Slower-X effect). We extended this
model to explore the effect of sex-specific selection on degeneration of sex
chromosomes, showing theoretically that male-limited genes degenerate on the X
chromosome and female-biased genes degenerate on the Y chromosome. This
prediction depends on the effective population size and the mutation rate, explaining
the variety of sex chromosome degeneration patterns observed in nature.
To test for direct evidence of a Slower-X (or Slower-Z) effect, we analyzed the
ZW sex chromosomes of the flatworm Schistosoma japonicum, which have a very
young non-recombining region with non-degenerated W. Diploid Z-linked genes have
higher ratios of non-synonymous to synonymous polymorphisms than autosomal
genes, supporting reduced efficiency of selection on the diploid Z region. These results
provide evidence of sheltering by the W chromosome, a mechanism that could
contribute to Z (X) chromosome degeneration, and illustrate contrasting evolutionary
patterns in old and young sex chromosome regions. In addition, genes with sexspecific patterns of expression show opposite patterns of selection in the young
(diploid) and old (hemizygous) Z, showing the complex manner in which sex-specific selection shapes the evolutionary patterns of sex chromosomes. },
author = {Mrnjavac, Andrea},
issn = {2663-337X},
keywords = {Sex chromosomes, evolution, selection, sheltering},
pages = {181},
publisher = {Institute of Science and Technology Austria},
title = {{Early stages of sex chromosome evolution}},
doi = {10.15479/at:ista:18531},
year = {2024},
}
@unpublished{18549,
abstract = {Sex-linked and autosomal loci experience different selective pressures and
evolutionary dynamics. X (or Z) chromosomes are often hemizygous, as Y (or W)
chromosomes often degenerate. Such hemizygous regions can be under greater
efficacy of selection, as recessive mutations are immediately exposed to selection in
the heterogametic sex (the so-called Faster-X or Faster-Z effect). However, in young
non-recombining regions, Y/W chromosomes often have many functional genes, and
many X/Z-linked loci are therefore diploid. The sheltering of recessive mutations on
the X/Z by the Y/W homolog is expected to drive a Slower-X (Slower-Z) effect for
diploid X/Z loci, i.e. a reduction in the efficacy of selection. While the Faster-X effect
has been studied extensively, much less is known empirically about the evolutionary
dynamics of diploid X or Z chromosomes. Here, we took advantage of published
population genomic data in the female-heterogametic human parasite Schistosoma
japonicum to characterize the gene content and diversity levels of the diploid and
hemizygous regions of the Z chromosome. We used different metrics of selective
pressures acting on genes to test for differences in the efficacy of selection in
hemizygous and diploid Z regions, relative to autosomes. We found consistent
patterns suggesting reduced Ne, and reduced efficacy of purifying selection, on both
hemizygous and diploid Z regions. Moreover, relaxed selection was particularly
pronounced for female-biased genes on the diploid Z, as predicted by Slower-Z
theory.
},
author = {Mrnjavac, Andrea and Vicoso, Beatriz},
booktitle = {bioRxiv},
title = {{Evidence of a Slower-Z effect in Schistosoma japonicum}},
doi = {10.1101/2024.07.02.601697},
year = {2024},
}
@phdthesis{18642,
abstract = {This thesis consists of two pieces of work in the broader feld of computational biology,
both of which are methods for the analysis of large scale biological data, implemented in
efcient software.
Chapter 2 introduces a statistical software for causal discovery and inference from observed
genetic marker and phenotypic trait data. We explore in simulation how well the method
can fne-map genetic efects, fnd the correct causal structure among tens of traits and
millions of genetic markers, and infer the causal efect size for the discovered causal
relations. We then apply the method to 8 million markers and 17 traits from the UK
Biobank and show that many relationships found with other methods are likely due to
the efects of hidden confounders.
Chapter 3 describes how this method can be applied to longitudinal data. I show how one
can incorporate the background knowledge present in the known order of measurements to
improve the accuracy of the causal discovery process, and explore the method’s ability to
identify age specifc genetic efects, and how the error rates of this recovery are infuenced
by missing data due to diferent censoring mechanisms.
Chapter 4 introduces a statistical software for the comparison of chromatin contact maps
based on the structural similarity index. We explore the robustness of the method to
noise and size diferences of the compared maps, show how it can measure evolutionary
conservation of topological features by providing a similarity ranking of syntenic regions,
and fnally how it can detect alterations in 3D genome structure due to genetic mutations
in samples of medical relevance.
},
author = {Machnik, Nick N},
issn = {2663-337X},
pages = {138},
publisher = {Institute of Science and Technology Austria},
title = {{Algorithms for causal learning and comparative analysis for genomic data}},
doi = {10.15479/at:ista:18642},
year = {2024},
}