---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '17885'
abstract:
- lang: eng
  text: 'The formation of new ribosomes is tightly coordinated with cell growth and
    proliferation. In eukaryotes, the correct assembly of all ribosomal proteins and
    RNAs follows an intricate scheme of maturation and rearrangement steps across
    three cellular compartments: the nucleolus, nucleoplasm, and cytoplasm. We demonstrate
    that usnic acid, a lichen secondary metabolite, inhibits the maturation of the
    large ribosomal subunit in yeast. We combine biochemical characterization of pre-ribosomal
    particles with a quantitative single-particle cryo-EM approach to monitor changes
    in nucleolar particle populations upon drug treatment. Usnic acid rapidly blocks
    the transition from nucleolar state B to C of Nsa1-associated pre-ribosomes, depleting
    key maturation factors such as Dbp10 and hindering pre-rRNA processing. This primary
    nucleolar block rapidly rebounds on earlier stages of the pathway which highlights
    the regulatory linkages between different steps. In summary, we provide an in-depth
    characterization of the effect of usnic acid on ribosome biogenesis, which may
    have implications for its reported anti-cancer activities.'
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: We thank Michael A. McAlear, Micheline Fromont-Racin, Philipp Milkereit,
  Arlen W. Johnson, Sabine Rospert, Ed Hurt, C. Yam, Günter Daum, Wolfgang Zachariae,
  Katrin Karbstein, Juan P. G. Ballesta, Mercedes Dosil, Miguel Remacha und Jesus
  de la Cruz for sharing strains or providing antibodies. We thank the members of
  the Bergler lab and the Haselbach lab for their helpful discussion. We thank Ellen
  Zhong for helpful discussions about the quantitative cryoDRGN analysis. This research
  was supported by the Scientific Service Units of IST Austria through resources provided
  by the Electron Microscopy Facility. This research was funded in whole, or in part,
  by the Austrian Science Foundation grants [https://doi.org/10.55776/P32977], [https://doi.org/10.55776/P29451]
  and [https://doi.org/10.55776/P32536] (to H.B.). Research at the IMP is generously
  supported by Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter
  grant FFG-852936). For the purpose of open access, the author has applied a CC BY
  public copyright licence to any Author Accepted Manuscript version arising from
  this submission.
article_number: '7511'
article_processing_charge: Yes
article_type: original
author:
- first_name: Lisa
  full_name: Kofler, Lisa
  last_name: Kofler
- first_name: Lorenz
  full_name: Grundmann, Lorenz
  last_name: Grundmann
- first_name: Magdalena
  full_name: Gerhalter, Magdalena
  last_name: Gerhalter
- first_name: Michael
  full_name: Prattes, Michael
  last_name: Prattes
- first_name: Juliane
  full_name: Merl-Pham, Juliane
  last_name: Merl-Pham
- first_name: Gertrude
  full_name: Zisser, Gertrude
  last_name: Zisser
- first_name: Irina
  full_name: Grishkovskaya, Irina
  last_name: Grishkovskaya
- first_name: Victor-Valentin
  full_name: Hodirnau, Victor-Valentin
  id: 3661B498-F248-11E8-B48F-1D18A9856A87
  last_name: Hodirnau
  orcid: 0000-0003-3904-947X
- first_name: Martin
  full_name: Vareka, Martin
  last_name: Vareka
- first_name: Rolf
  full_name: Breinbauer, Rolf
  last_name: Breinbauer
- first_name: Stefanie M.
  full_name: Hauck, Stefanie M.
  last_name: Hauck
- first_name: David
  full_name: Haselbach, David
  last_name: Haselbach
- first_name: Helmut
  full_name: Bergler, Helmut
  last_name: Bergler
citation:
  ama: Kofler L, Grundmann L, Gerhalter M, et al. The novel ribosome biogenesis inhibitor
    usnic acid blocks nucleolar pre-60S maturation. <i>Nature Communications</i>.
    2024;15. doi:<a href="https://doi.org/10.1038/s41467-024-51754-3">10.1038/s41467-024-51754-3</a>
  apa: Kofler, L., Grundmann, L., Gerhalter, M., Prattes, M., Merl-Pham, J., Zisser,
    G., … Bergler, H. (2024). The novel ribosome biogenesis inhibitor usnic acid blocks
    nucleolar pre-60S maturation. <i>Nature Communications</i>. Springer Nature. <a
    href="https://doi.org/10.1038/s41467-024-51754-3">https://doi.org/10.1038/s41467-024-51754-3</a>
  chicago: Kofler, Lisa, Lorenz Grundmann, Magdalena Gerhalter, Michael Prattes, Juliane
    Merl-Pham, Gertrude Zisser, Irina Grishkovskaya, et al. “The Novel Ribosome Biogenesis
    Inhibitor Usnic Acid Blocks Nucleolar Pre-60S Maturation.” <i>Nature Communications</i>.
    Springer Nature, 2024. <a href="https://doi.org/10.1038/s41467-024-51754-3">https://doi.org/10.1038/s41467-024-51754-3</a>.
  ieee: L. Kofler <i>et al.</i>, “The novel ribosome biogenesis inhibitor usnic acid
    blocks nucleolar pre-60S maturation,” <i>Nature Communications</i>, vol. 15. Springer
    Nature, 2024.
  ista: Kofler L, Grundmann L, Gerhalter M, Prattes M, Merl-Pham J, Zisser G, Grishkovskaya
    I, Hodirnau V-V, Vareka M, Breinbauer R, Hauck SM, Haselbach D, Bergler H. 2024.
    The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation.
    Nature Communications. 15, 7511.
  mla: Kofler, Lisa, et al. “The Novel Ribosome Biogenesis Inhibitor Usnic Acid Blocks
    Nucleolar Pre-60S Maturation.” <i>Nature Communications</i>, vol. 15, 7511, Springer
    Nature, 2024, doi:<a href="https://doi.org/10.1038/s41467-024-51754-3">10.1038/s41467-024-51754-3</a>.
  short: L. Kofler, L. Grundmann, M. Gerhalter, M. Prattes, J. Merl-Pham, G. Zisser,
    I. Grishkovskaya, V.-V. Hodirnau, M. Vareka, R. Breinbauer, S.M. Hauck, D. Haselbach,
    H. Bergler, Nature Communications 15 (2024).
das_tickbox: '1'
dataavailabilitystatement: Strains generated in this study are available from the
  corresponding authors upon request. For cryo-EM model building, published pre-60S
  models PDB-6EM3, PDB-6EM4, PDB-6C0F, PDB-6EM1 and PDB-8V87 were used. Motion-corrected
  micrographs with annotated particle locations were deposited in EMPIAR with the
  accession number EMPIAR-12237. The cryo-EM maps of clusters 1 to 4 with the combined
  datasets were deposited in the EMDB with the accession numbers EMD-51122, EMD-51126,
  EMD-51128, and EMD-51129. The reconstructions for the treated dataset were deposited
  with the accession numbers EMD-51175, EMD-51176, EMD-51177, and EMD-51178, while
  the untreated reconstructions of reported clusters can be found via EMD-51164, EMD-51165,
  EMD-51166, EMD-51167. The mass spectrometry proteomics data have been deposited
  to the ProteomeXchange Consortium via the PRIDE101 partner repository with the dataset
  identifier PXD046691. Source data are provided with this paper.
date_created: 2024-09-08T22:01:10Z
date_published: 2024-08-29T00:00:00Z
date_updated: 2026-10-01T11:05:46Z
day: '29'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.1038/s41467-024-51754-3
external_id:
  isi:
  - '001457895200001'
  pmid:
  - '39209816'
file:
- access_level: open_access
  checksum: 7c044538a47182c826d1b526c52958a2
  content_type: application/pdf
  creator: dernst
  date_created: 2024-09-09T08:56:12Z
  date_updated: 2024-09-09T08:56:12Z
  file_id: '17946'
  file_name: 2024_NatureComm_Kofler.pdf
  file_size: 3735024
  relation: main_file
  success: 1
file_date_updated: 2024-09-09T08:56:12Z
fulldoi: https://doi.org/10.1038/s41467-024-51754-3
has_accepted_license: '1'
intvolume: '        15'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S
  maturation
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 15
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '23023'
abstract:
- lang: eng
  text: "In this repository, you will find the R-scripts used to generate the figures,
    along with the data necessary to make the plots. You will also find the Python-scripts
    used to compute the pair-wise distance between embryos, to estimate the surface,
    the volume, the α-parameter, to identify the closest rigid packing and to generate
    the morphomap. Additionally, you have access to the base model used with Plantseg
    to predict and label the cells at the 8-cell stage. Note that a more accurate
    and more specific model was generated for each embryo based on the curation of
    at least 5 timepoints.\r\n\r\nFigures\r\nThe plots in Figure 1-7 and Figure S1-S7
    can be generated with the respective files. The code is written in R and requires
    RStudio to work out-of-the-box. The R scripts are located in figures/. Figures
    and supplemental figures are generated with the same file (e.g., Figure 1.R generates
    all the computed panels of Figure 1 and Figure S1). Data required to generate
    the plots are located in figures/data/. Note that the code to work with the morphomap
    and the tracking data is located in local packages figures/fabreges.morphomap
    and figures/fabreges.tracking. An additional package figures/fabreges.generic
    contains utility functions.\r\n\r\nPython packages\r\nFor the needs of this study,
    we developed a series of package for Python located in python-packages/. The packages
    can be directly imported within your scripts. Along with the packages, you will
    find 6 scripts used to compute, extract or estimate the data from the source.
    The folder is organised as follow:\r\n\r\npackage interfaces is located in python-packages/interfaces/
    and can be tested by running the scripts to extract the angles an estimate the
    surface of contact (compute-angles.py and estimate-contacts.py respectively) in
    folder python-packages,\r\npackage morphomap is located in python-packages/morphomap/
    and can be tested by running the script to compute the geometrical distances between
    embryos, project the data in 2D and compute the volume of the cells (compute-distances.py,
    process-distances.py and compute-volumes.py respectively) in folder python-packages,\r\npackage
    splinefit is included in morphomap in python-packages/morphomap/splinefit/, but
    can function independently,\r\npackage rbb is located in python-packages/rbb/
    and can be tested by running the script to identify the closest rigid packing
    of an embryo at the 8-cell stage (identify-packing.py) in folder python-packages.\r\nWe
    provide example of segmented data in python-packages/samples/.\r\n\r\nCNN\r\nWe
    provide a convolutional neural network (CNN) used in our study, located in cnn.
    Please note that we optimised the CNN further for each dataset by doing manual
    curation of at least 5 time points and by retraining the network with those ground
    truth. The CNN were trained using pytorch-3dunet. The CNN can be used with Plantseg.
    Currently (plantseg v.1.6.0 and pytorch-3dunet v.1.6.0), the output model from
    pytorch-3dunet must currently be modified to work with plantseg:\r\n\r\n# python\r\nimport
    torch\r\nfor model in ('best_checkpoint.pytorch', 'last_checkpoint.pytorch'):\r\n
    \   state = torch.load(model, map_location='cpu')\r\n    state = state['model_state_dict']\r\n
    \   torch.save(state, model)\r\n\r\nRequierements\r\nFigures\r\nThe figures were
    generated with R (v. 4.4.0) and RStudio (v. 2024.04.1+748). The following packages
    must be installed prior to execution:\r\n\r\nalphashape3d (v. 1.3.2)\r\ndevtools
    (v. 2.4.5)\r\nggplot2 (v. 3.5.1)\r\nggrepel (v. 0.9.5)\r\nrstudioapi (v. 0.16.0)\r\nTo
    install all these packages, run the following command in the RStudio console:\r\n\r\n#
    R\r\ninstall.packages(c(\"alphashape3d@1.3.2\", \"devtools@2.4.5\", \"ggplot2@3.5.1\",
    \"ggrepel@0.9.5\", \"rstudioapi@0.16\"))\r\n\r\nMore recent version of R, RStudio
    and the packages may also work (not tested).\r\n\r\nPython packages\r\nPython
    3.12.3 was used to analyse the data. The scripts may work with more recent version
    of Python and with Python 3.8 or earlier (not tested). To run the code, you must
    first install the following packages:\r\n\r\nnumpy (v. 1.26.4)\r\nimageio (v.
    2.34.1)\r\nscipy (v. 1.13.1)\r\nscikit-image (v. 0.23.2)\r\nscikit-learn (v. 1.5.0)\r\nAlternatively,
    you can create a conda environment:\r\n\r\n# Shell script\r\nconda create -y --name
    fabreges2024 python=3.12.3\r\nconda activate fabreges2024\r\npython -m pip install
    numpy==1.26.4 imageio==2.34.1 scipy==1.13.1 scikit-image==0.23.2 scikit-learn==1.5.0\r\n\r\nMore
    recent version of the dependencies may work (not tested).\r\n\r\nUsage\r\nFigures\r\nOpen
    one of the figure script in RStudio and run the entire code. You may have to create
    a folder output in figures/ if it does not exist.\r\n\r\nThe code has local dependencies
    that will be installed on your computer when encountering them for the first time.
    They start with fabreges.* and are necessary to generate the figures.\r\n\r\nPython
    packages (example)\r\nCompute angles\r\n# Shell script\r\n# Compute a summary
    (mean, median, s.d.) of the angles in embryo C1 at time 40\r\npython compute-angles.py
    -s -r 15 -R 20 samples/C1_t040.tif.gz output/C1_t040_angles.csv\r\n# Compute a
    detailed list of angle values\r\npython compute-angles.py -r 15 -R 20 samples/C1_t041.tif.gz
    output/C1_t041_angles.csv\r\n\r\nCompute distances\r\n# Shell script\r\n# Compute
    the distance between two embryos\r\npython compute-distances.py -c 5 -s 5 samples/C1_t040.tif.gz
    samples/C1_t041.tif.gz output/distances.csv\r\n# Append another distance measurement\r\npython
    compute-distances.py -a -c 5 -s 5 samples/C1_t040.tif.gz samples/C1_t042.tif.gz
    output/distances.csv\r\n\r\nCompute volumes\r\n# Shell script\r\n# Compute the
    volume in isotropic data\r\npython compute-volumes.py -r 0.416 0.416 0.416 samples/C1_t040.tif.gz
    output/volumes.csv\r\n\r\nEstimate contacts\r\n# Shell script\r\n# Estimate the
    contacts and the free surface area\r\npython estimate-contacts.py -r 0.416 0.416
    0.416 samples/C1_t040.tif.gz output/contacts.csv\r\n\r\nIdentify the closest rigid
    packing\r\n# Shell script\r\n# Assuming the file `output/contacts.csv` exists
    and contains the output\r\n# from command `estimate-contacts.py`.\r\n# Identify
    the closest rigid packings\r\npython identify-packing.py output/contacts.csv output/backbones.csv\r\n\r\nGenerate
    the seeds for Surface Evolver\r\n# Shell script\r\n# Assuming the file `output/contacts.csv`
    exists and contains the output\r\n# from command `estimate-contacts.py`, and the
    file `output/volumes.csv`\r\n# exists and contains the output from command `compute-volumes.py`\r\n#
    Generate the seeds for Surface Evolver using automatic thresholding\r\n# Automatic
    threshold will determine the highest cell-cell contact threshold\r\n# that preserves
    rigidity of the embryo (or 0 if not rigid)\r\npython generate-seed.py output/contacts.csv
    output/volumes.csv output/seed.fe\r\n# Generate the seeds for Surface Evolver
    with custom threshold\r\npython generate-seed.py --threshold 0.1 output/contacts.csv
    output/volumes.csv output/seed.fe\r\n\r\nProject in 2D and generate a distance
    matrix\r\n# Shell script\r\n# Assuming the folder `foo` only contains one or more
    CSV\r\n# from command `compute-distances.py`.\r\n\r\n# Compute the tSNE 2D projection\r\npython
    process-distances.py -D2 -t output/tsne_2d.csv foo/\r\n\r\n# Compute the tSNE
    3D projection\r\npython process-distances.py -D3 -t output/tsne_2d.csv foo/\r\n\r\n#
    Generate the distance matrix\r\npython process-distances.py -m output/dismat.csv
    foo/"
article_processing_charge: No
author:
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  last_name: Corominas-Murtra
- first_name: Prachiti
  full_name: '  Moghe, Prachiti'
  last_name: '  Moghe'
- first_name: Alison
  full_name: Kickuth, Alison
  last_name: Kickuth
- first_name: Takafumi
  full_name: Ichikawa, Takafumi
  last_name: Ichikawa
- first_name: Chizuru
  full_name: Iwatani, Chizuru
  last_name: Iwatani
- first_name: Tomoyuki
  full_name: Tsukiyama, Tomoyuki
  last_name: Tsukiyama
- first_name: Nathalie
  full_name: Daniel, Nathalie
  last_name: Daniel
- first_name: Julie
  full_name: Gering, Julie
  last_name: Gering
- first_name: Anniek
  full_name: Stokkermans, Anniek
  last_name: Stokkermans
- first_name: Adrian
  full_name: Wolny, Adrian
  last_name: Wolny
- first_name: Anna
  full_name: Kreshuk, Anna
  last_name: Kreshuk
- first_name: Véronique
  full_name: Duranthon, Véronique
  last_name: Duranthon
- first_name: Virginie
  full_name: Uhlmann, Virginie
  last_name: Uhlmann
- first_name: Edouard
  full_name: Hannezo, Edouard
  last_name: Hannezo
- first_name: Takashi
  full_name: Hiiragi, Takashi
  last_name: Hiiragi
citation:
  ama: 'Corominas-Murtra B,   Moghe P, Kickuth A, et al. Data and software from: Temporal
    variability and cell mechanics control robustness in mammalian embryogenesis.
    2024. doi:<a href="https://doi.org/10.5281/zenodo.12819780">10.5281/zenodo.12819780</a>'
  apa: 'Corominas-Murtra, B.,   Moghe, P., Kickuth, A., Ichikawa, T., Iwatani, C.,
    Tsukiyama, T., … Hiiragi, T. (2024). Data and software from: Temporal variability
    and cell mechanics control robustness in mammalian embryogenesis. Institute of
    Science and Technology Austria. <a href="https://doi.org/10.5281/zenodo.12819780">https://doi.org/10.5281/zenodo.12819780</a>'
  chicago: 'Corominas-Murtra, Bernat, Prachiti   Moghe, Alison Kickuth, Takafumi Ichikawa,
    Chizuru Iwatani, Tomoyuki Tsukiyama, Nathalie Daniel, et al. “Data and Software
    from: Temporal Variability and Cell Mechanics Control Robustness in Mammalian
    Embryogenesis.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.5281/zenodo.12819780">https://doi.org/10.5281/zenodo.12819780</a>.'
  ieee: 'B. Corominas-Murtra <i>et al.</i>, “Data and software from: Temporal variability
    and cell mechanics control robustness in mammalian embryogenesis.” Institute of
    Science and Technology Austria, 2024.'
  ista: 'Corominas-Murtra B,   Moghe P, Kickuth A, Ichikawa T, Iwatani C, Tsukiyama
    T, Daniel N, Gering J, Stokkermans A, Wolny A, Kreshuk A, Duranthon V, Uhlmann
    V, Hannezo E, Hiiragi T. 2024. Data and software from: Temporal variability and
    cell mechanics control robustness in mammalian embryogenesis, Institute of Science
    and Technology Austria, <a href="https://doi.org/10.5281/zenodo.12819780">10.5281/zenodo.12819780</a>.'
  mla: 'Corominas-Murtra, Bernat, et al. <i>Data and Software from: Temporal Variability
    and Cell Mechanics Control Robustness in Mammalian Embryogenesis</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.5281/zenodo.12819780">10.5281/zenodo.12819780</a>.'
  short: B. Corominas-Murtra, P.   Moghe, A. Kickuth, T. Ichikawa, C. Iwatani, T.
    Tsukiyama, N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon,
    V. Uhlmann, E. Hannezo, T. Hiiragi, (2024).
contributor:
- contributor_type: contact_person
  first_name: Dimitri
  last_name: Fabrèges
date_created: 2026-10-01T10:54:27Z
date_published: 2024-07-25T00:00:00Z
date_updated: 2026-10-01T10:54:33Z
day: '25'
department:
- _id: EdHa
doi: 10.5281/zenodo.12819780
fulldoi: https://doi.org/10.5281/zenodo.12819780
main_file_link:
- open_access: '1'
  url: https://doi.org/10.5281/zenodo.12819780
month: '07'
oa: 1
oa_version: None
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '18446'
    relation: used_in_publication
    status: public
status: public
title: 'Data and software from: Temporal variability and cell mechanics control robustness
  in mammalian embryogenesis'
type: research_data_reference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18913'
abstract:
- lang: eng
  text: "With the proliferation of blockchain technology in high-value sectors, consensus
    protocols are becoming critical infrastructures. The rapid innovation cycle in
    Byzantine fault tolerant (BFT) consensus protocols has culminated in HotStuff,
    which provides linear message complexity in the partially synchronous setting.
    To achieve this, HotStuff leverages a leader that collects, aggregates, and broadcasts
    the messages of other validators. This paper analyzes the security implications
    of such approaches in practice, from the perspective of liveness and availability.\r\nBy
    implementing attacks in a globally-distributed testbed, we show that state-of-the-art
    leader-based protocols are vulnerable to denial-of-service (DoS) attacks on the
    leader. Our attacks, demonstrated on committees of up to 64 validators, manage
    to disrupt liveness within seconds, using only a few tens of Mbps of attack bandwidth
    per validator. Crucially, the cost and effectiveness of the attacks are independent
    of the committee size. Based on the outcome of these experiments, we then propose
    and test effective mitigations. Our findings show that advancements in both protocol
    design and network-layer defenses can greatly improve the practical resilience
    of BFT consensus protocols."
acknowledgement: This work was mostly realized while Alberto Sonnino and Lefteris
  Kokoris-Kogias were employed at Meta. We gratefully acknowledge support for this
  project from ETH Zurich and Mysten Labs.
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Giacomo
  full_name: Giuliari, Giacomo
  last_name: Giuliari
- first_name: Alberto
  full_name: Sonnino, Alberto
  last_name: Sonnino
- first_name: Marc
  full_name: Frei, Marc
  last_name: Frei
- first_name: Fabio
  full_name: Streun, Fabio
  last_name: Streun
- first_name: Eleftherios
  full_name: Kokoris Kogias, Eleftherios
  id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
  last_name: Kokoris Kogias
  orcid: 0000-0002-8827-3382
- first_name: Adrian
  full_name: Perrig, Adrian
  last_name: Perrig
citation:
  ama: 'Giuliari G, Sonnino A, Frei M, Streun F, Kokoris Kogias E, Perrig A. An empirical
    study of consensus protocols’ DoS resilience. In: <i>Proceedings of the 19th ACM
    Asia Conference on Computer and Communications Security</i>. ACM; 2024:1345-1360.
    doi:<a href="https://doi.org/10.1145/3634737.3656997">10.1145/3634737.3656997</a>'
  apa: 'Giuliari, G., Sonnino, A., Frei, M., Streun, F., Kokoris Kogias, E., &#38;
    Perrig, A. (2024). An empirical study of consensus protocols’ DoS resilience.
    In <i>Proceedings of the 19th ACM Asia Conference on Computer and Communications
    Security</i> (pp. 1345–1360). Singapore, Singapore: ACM. <a href="https://doi.org/10.1145/3634737.3656997">https://doi.org/10.1145/3634737.3656997</a>'
  chicago: Giuliari, Giacomo, Alberto Sonnino, Marc Frei, Fabio Streun, Eleftherios
    Kokoris Kogias, and Adrian Perrig. “An Empirical Study of Consensus Protocols’
    DoS Resilience.” In <i>Proceedings of the 19th ACM Asia Conference on Computer
    and Communications Security</i>, 1345–60. ACM, 2024. <a href="https://doi.org/10.1145/3634737.3656997">https://doi.org/10.1145/3634737.3656997</a>.
  ieee: G. Giuliari, A. Sonnino, M. Frei, F. Streun, E. Kokoris Kogias, and A. Perrig,
    “An empirical study of consensus protocols’ DoS resilience,” in <i>Proceedings
    of the 19th ACM Asia Conference on Computer and Communications Security</i>, Singapore,
    Singapore, 2024, pp. 1345–1360.
  ista: 'Giuliari G, Sonnino A, Frei M, Streun F, Kokoris Kogias E, Perrig A. 2024.
    An empirical study of consensus protocols’ DoS resilience. Proceedings of the
    19th ACM Asia Conference on Computer and Communications Security. ASIACCS: Asia
    Conference on Computer and Communications Security, 1345–1360.'
  mla: Giuliari, Giacomo, et al. “An Empirical Study of Consensus Protocols’ DoS Resilience.”
    <i>Proceedings of the 19th ACM Asia Conference on Computer and Communications
    Security</i>, ACM, 2024, pp. 1345–60, doi:<a href="https://doi.org/10.1145/3634737.3656997">10.1145/3634737.3656997</a>.
  short: G. Giuliari, A. Sonnino, M. Frei, F. Streun, E. Kokoris Kogias, A. Perrig,
    in:, Proceedings of the 19th ACM Asia Conference on Computer and Communications
    Security, ACM, 2024, pp. 1345–1360.
conference:
  end_date: 2024-07-05
  location: Singapore, Singapore
  name: 'ASIACCS: Asia Conference on Computer and Communications Security'
  start_date: 2024-07-01
das_tickbox: '0'
date_created: 2025-01-27T13:57:00Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-10-01T11:04:34Z
day: '01'
ddc:
- '000'
department:
- _id: ElKo
doi: 10.1145/3634737.3656997
external_id:
  isi:
  - '001283918100095'
file:
- access_level: open_access
  checksum: 1e743ddf49d35390eb56e11eb0759150
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  creator: dernst
  date_created: 2025-01-27T14:04:12Z
  date_updated: 2025-01-27T14:04:12Z
  file_id: '18914'
  file_name: 2024_ACMAsiaCCS_Giuliari.pdf
  file_size: 951940
  relation: main_file
  success: 1
file_date_updated: 2025-01-27T14:04:12Z
fulldoi: https://doi.org/10.1145/3634737.3656997
has_accepted_license: '1'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1345-1360
publication: Proceedings of the 19th ACM Asia Conference on Computer and Communications
  Security
publication_identifier:
  isbn:
  - '9798400704826'
publication_status: published
publisher: ACM
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: An empirical study of consensus protocols’ DoS resilience
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: repository
OA_type: hybrid
_id: '18957'
abstract:
- lang: eng
  text: Sui Lutris is the first smart-contract platform to sustainably achieve sub-second
    finality. It achieves this significant decrease by employing consensusless agreement
    not only for simple payments but for a large variety of transactions. Unlike prior
    work, Sui Lutris neither compromises expressiveness nor throughput and can run
    perpetually without restarts. Sui Lutris achieves this by safely integrating consensuless
    agreement with a high-throughput consensus protocol that is invoked out of the
    critical finality path but ensures that when a transaction is at risk of inconsistent
    concurrent accesses, its settlement is delayed until the total ordering is resolved.
    Building such a hybrid architecture is especially delicate during reconfiguration
    events, where the system needs to preserve the safety of the consensusless path
    without compromising the long-term liveness of potentially misconfigured clients.
    We thus develop a novel reconfiguration protocol, the first to provably show the
    safe and efficient reconfiguration of a consensusless blockchain. Sui Lutris is
    currently running in production and underpins the Sui smart-contract platform.
    Combined with the use of Objects instead of accounts it enables the safe execution
    of smart contracts that expose objects as a first-class resource. In our experiments
    Sui Lutris achieves latency lower than 0.5 seconds for throughput up to 5,000
    certificates per second (150k ops/s with transaction blocks), compared to the
    state-of-the-art real-world consensus latencies of 3 seconds. Furthermore, it
    gracefully handles validators crash-recovery and does not suffer visible performance
    degradation during reconfiguration.
acknowledgement: 'This work is funded by MystenLabs. We thank the Mysten Labs Engineering
  teams for valuable feedback broadly, and specifically Dmitry Perelman and Todd Fiala
  for managing the implementation effort. A number of folks contributed to specific
  aspects of the implementation of Sui Lutris (amongst many other contributions to
  the overall blockchain): Francois Garillot, Laura Makdah, Mingwei Tian, Andrew Schran,
  Sadhan Sood and William Smith implemented and optimized aspects of both Sui Lutris
  and Narwhal / Bullshark consensus; Alonso de Gortari oversaw the cryptoeconomics
  of the blockchain, and Emma Zhong, Ade Adepoju, Tim Zakia and Dario Russi designed
  and implemented staking and gas mechanisms. Adam Welc designed several Move tools
  and provided great feedback on the manuscript. We also extend our thanks to Patrick
  Kuo, Ge Gao, Chris Li, and Arun Koshy for their work on the Sui Lutris SDK, clients,
  and RPC layer; Kostas Chalkias, Jonas Lindstrøm, and Joy Wang built cryptographic
  components.'
article_processing_charge: No
arxiv: 1
author:
- first_name: Sam
  full_name: Blackshear, Sam
  last_name: Blackshear
- first_name: Andrey
  full_name: Chursin, Andrey
  last_name: Chursin
- first_name: George
  full_name: Danezis, George
  last_name: Danezis
- first_name: Anastasios
  full_name: Kichidis, Anastasios
  last_name: Kichidis
- first_name: Eleftherios
  full_name: Kokoris Kogias, Eleftherios
  id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
  last_name: Kokoris Kogias
  orcid: 0000-0002-8827-3382
- first_name: Xun
  full_name: Li, Xun
  last_name: Li
- first_name: Mark
  full_name: Logan, Mark
  last_name: Logan
- first_name: Ashok
  full_name: Menon, Ashok
  last_name: Menon
- first_name: Todd
  full_name: Nowacki, Todd
  last_name: Nowacki
- first_name: Alberto
  full_name: Sonnino, Alberto
  last_name: Sonnino
- first_name: Brandon
  full_name: Williams, Brandon
  last_name: Williams
- first_name: Lu
  full_name: Zhang, Lu
  last_name: Zhang
citation:
  ama: 'Blackshear S, Chursin A, Danezis G, et al. Sui Lutris: A blockchain combining
    broadcast and consensus. In: <i>Proceedings of the 2024 on ACM SIGSAC Conference
    on Computer and Communications Security</i>. ACM; 2024:2606-2620. doi:<a href="https://doi.org/10.1145/3658644.3670286">10.1145/3658644.3670286</a>'
  apa: 'Blackshear, S., Chursin, A., Danezis, G., Kichidis, A., Kokoris Kogias, E.,
    Li, X., … Zhang, L. (2024). Sui Lutris: A blockchain combining broadcast and consensus.
    In <i>Proceedings of the 2024 on ACM SIGSAC Conference on Computer and Communications
    Security</i> (pp. 2606–2620). Salt Lake City, UT, United States: ACM. <a href="https://doi.org/10.1145/3658644.3670286">https://doi.org/10.1145/3658644.3670286</a>'
  chicago: 'Blackshear, Sam, Andrey Chursin, George Danezis, Anastasios Kichidis,
    Eleftherios Kokoris Kogias, Xun Li, Mark Logan, et al. “Sui Lutris: A Blockchain
    Combining Broadcast and Consensus.” In <i>Proceedings of the 2024 on ACM SIGSAC
    Conference on Computer and Communications Security</i>, 2606–20. ACM, 2024. <a
    href="https://doi.org/10.1145/3658644.3670286">https://doi.org/10.1145/3658644.3670286</a>.'
  ieee: 'S. Blackshear <i>et al.</i>, “Sui Lutris: A blockchain combining broadcast
    and consensus,” in <i>Proceedings of the 2024 on ACM SIGSAC Conference on Computer
    and Communications Security</i>, Salt Lake City, UT, United States, 2024, pp.
    2606–2620.'
  ista: 'Blackshear S, Chursin A, Danezis G, Kichidis A, Kokoris Kogias E, Li X, Logan
    M, Menon A, Nowacki T, Sonnino A, Williams B, Zhang L. 2024. Sui Lutris: A blockchain
    combining broadcast and consensus. Proceedings of the 2024 on ACM SIGSAC Conference
    on Computer and Communications Security. CCS: Conference on Computer and Communications
    Security, 2606–2620.'
  mla: 'Blackshear, Sam, et al. “Sui Lutris: A Blockchain Combining Broadcast and
    Consensus.” <i>Proceedings of the 2024 on ACM SIGSAC Conference on Computer and
    Communications Security</i>, ACM, 2024, pp. 2606–20, doi:<a href="https://doi.org/10.1145/3658644.3670286">10.1145/3658644.3670286</a>.'
  short: S. Blackshear, A. Chursin, G. Danezis, A. Kichidis, E. Kokoris Kogias, X.
    Li, M. Logan, A. Menon, T. Nowacki, A. Sonnino, B. Williams, L. Zhang, in:, Proceedings
    of the 2024 on ACM SIGSAC Conference on Computer and Communications Security,
    ACM, 2024, pp. 2606–2620.
conference:
  end_date: 2024-10-18
  location: Salt Lake City, UT, United States
  name: 'CCS: Conference on Computer and Communications Security'
  start_date: 2024-10-14
das_tickbox: '0'
date_created: 2025-01-29T12:42:21Z
date_published: 2024-12-09T00:00:00Z
date_updated: 2026-10-01T11:04:52Z
day: '09'
department:
- _id: ElKo
doi: 10.1145/3658644.3670286
external_id:
  arxiv:
  - '2310.18042'
  isi:
  - '001436367300178'
fulldoi: https://doi.org/10.1145/3658644.3670286
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2310.18042
month: '12'
oa: 1
oa_version: Preprint
page: 2606-2620
publication: Proceedings of the 2024 on ACM SIGSAC Conference on Computer and Communications
  Security
publication_identifier:
  isbn:
  - '9798400706363'
publication_status: published
publisher: ACM
quality_controlled: '1'
researchdata_availability: no
status: public
supplementarymaterial: no
title: 'Sui Lutris: A blockchain combining broadcast and consensus'
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '17269'
abstract:
- lang: eng
  text: The directed migration of epithelial cell collectives through coordinated
    movements plays a crucial role in various physiological processes and is increasingly
    understood at the level of large confluent monolayers. However, numerous processes
    rely on the migration of small groups of polarized epithelial clusters in complex
    environments, and their responses to external geometries remain poorly understood.
    To address this, we cultivate primary epithelial keratocyte tissues on adhesive
    microstripes to create autonomous epithelial clusters with well-defined geometries.
    We show that their migration efficiency is strongly influenced by the contact
    geometry and the orientation of cell–cell contacts with respect to the direction
    of migration. A combination of velocity and polarity alignment with contact regulation
    of locomotion in an active matter model captures quantitatively the experimental
    data. Furthermore, we predict that this combination of rules enables efficient
    navigation in complex geometries, which we confirm experimentally. Altogether,
    our findings provide a conceptual framework for extracting the interaction rules
    of active systems from their interaction with physical boundaries, as well as
    design principles for collective navigation in complex microenvironments.
acknowledgement: M.L., E.V. and S.G. acknowledge funding from the European Regional
  Development Fund (ERDF) Prostem Research Project (No. 1510614, Wallonia DG06), the
  Epiforce Project of the National Fund for Scientific Research, Belgium (FRS-FNRS;
  Project No. T.0092.21), the Cellsqueezer Project of FRS-FNRS (Project No. J.0061.23),
  the Optopattern Project of FRS-FNRS (Project no. U.NO26.22) and the Interreg MAT(T)ISSE
  project, which is financially supported by Interreg France-Wallonie-Vlaanderen,
  ERDF). A.R. and M.L. are financially supported by FRS-FNRS as a research fellow
  (Aspirant FNRS) and Postdoctoral Researcher (Chargée de Recherches FNRS), respectively.
  E.V. and Y.K. are financially supported by FRS-FNRS through grants from the Fund
  for Research Training in Industry and Agriculture (FRIA). This project was supported
  by the European Research Council under the European Union’s Horizon 2020 Research
  and Innovation Programme (Grant Agreement No. 851288 to E.H.) and Marie Skłodowska-Curie
  Actions (Grant Agreement No. 797621 to M.G.-G.). D.B.B. was supported by the NOMIS
  foundation as a NOMIS fellow and by the European Molecular Biology Organization
  (Postdoctoral Fellowship ALTF 343-2022) and performed this work in part at the Aspen
  Center for Physics, which is supported by the National Science Foundation (Grant
  No. PHY-1607611). X.T. and M.G.-G. acknowledge support from the Government of Catalonia
  (Grant No. AGAUR SGR-2017-01602 and a CERCA Programme), the Spanish Ministry for
  Science and Innovation and ERDF (Grant No. PGC2018-099645-B-I00), the European Research
  Council (Grant No. Adv-883739), Fundació la Marató de TV3 (201903-30-31-32), the
  European Commission (Grant No. H2020-FETPROACT-01-2016-731957), La Caixa Foundation
  and the Biomedical Research Center Consortium in Red (Grant No. CB15/00153) at the
  Carlos III Health Institute, Ministry of Science and Innovation. IBEC is recipient
  of a Severo Ochoa Award of Excellence from the Spanish Ministry of Economy, Trade
  and Business.
article_processing_charge: No
article_type: original
author:
- first_name: Eléonore
  full_name: Vercruysse, Eléonore
  last_name: Vercruysse
- first_name: David
  full_name: Brückner, David
  id: e1e86031-6537-11eb-953a-f7ab92be508d
  last_name: Brückner
  orcid: 0000-0001-7205-2975
- first_name: Manuel
  full_name: Gómez-González, Manuel
  last_name: Gómez-González
- first_name: Alexandre
  full_name: Remson, Alexandre
  last_name: Remson
- first_name: Marine
  full_name: Luciano, Marine
  last_name: Luciano
- first_name: Yohalie
  full_name: Kalukula, Yohalie
  last_name: Kalukula
- first_name: Leone
  full_name: Rossetti, Leone
  last_name: Rossetti
- first_name: Xavier
  full_name: Trepat, Xavier
  last_name: Trepat
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Sylvain
  full_name: Gabriele, Sylvain
  last_name: Gabriele
citation:
  ama: Vercruysse E, Brückner D, Gómez-González M, et al. Geometry-driven migration
    efficiency of autonomous epithelial cell clusters. <i>Nature Physics</i>. 2024;20:1492-1500.
    doi:<a href="https://doi.org/10.1038/s41567-024-02532-x">10.1038/s41567-024-02532-x</a>
  apa: Vercruysse, E., Brückner, D., Gómez-González, M., Remson, A., Luciano, M.,
    Kalukula, Y., … Gabriele, S. (2024). Geometry-driven migration efficiency of autonomous
    epithelial cell clusters. <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-024-02532-x">https://doi.org/10.1038/s41567-024-02532-x</a>
  chicago: Vercruysse, Eléonore, David Brückner, Manuel Gómez-González, Alexandre
    Remson, Marine Luciano, Yohalie Kalukula, Leone Rossetti, Xavier Trepat, Edouard
    B Hannezo, and Sylvain Gabriele. “Geometry-Driven Migration Efficiency of Autonomous
    Epithelial Cell Clusters.” <i>Nature Physics</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41567-024-02532-x">https://doi.org/10.1038/s41567-024-02532-x</a>.
  ieee: E. Vercruysse <i>et al.</i>, “Geometry-driven migration efficiency of autonomous
    epithelial cell clusters,” <i>Nature Physics</i>, vol. 20. Springer Nature, pp.
    1492–1500, 2024.
  ista: Vercruysse E, Brückner D, Gómez-González M, Remson A, Luciano M, Kalukula
    Y, Rossetti L, Trepat X, Hannezo EB, Gabriele S. 2024. Geometry-driven migration
    efficiency of autonomous epithelial cell clusters. Nature Physics. 20, 1492–1500.
  mla: Vercruysse, Eléonore, et al. “Geometry-Driven Migration Efficiency of Autonomous
    Epithelial Cell Clusters.” <i>Nature Physics</i>, vol. 20, Springer Nature, 2024,
    pp. 1492–500, doi:<a href="https://doi.org/10.1038/s41567-024-02532-x">10.1038/s41567-024-02532-x</a>.
  short: E. Vercruysse, D. Brückner, M. Gómez-González, A. Remson, M. Luciano, Y.
    Kalukula, L. Rossetti, X. Trepat, E.B. Hannezo, S. Gabriele, Nature Physics 20
    (2024) 1492–1500.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: All data are available from the corresponding authors upon
  request. Source data are provided with this paper.
date_created: 2024-07-16T12:32:17Z
date_published: 2024-09-01T00:00:00Z
date_updated: 2026-10-01T11:02:43Z
day: '01'
department:
- _id: EdHa
doi: 10.1038/s41567-024-02532-x
ec_funded: 1
external_id:
  isi:
  - '001250246200004'
fulldoi: https://doi.org/10.1038/s41567-024-02532-x
intvolume: '        20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.07.17.500364
month: '09'
oa: 1
oa_version: Preprint
page: 1492-1500
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b
  grant_number: ALTF 343-2022
  name: A mechano-chemical theory for stem cell fate decisions in organoid development
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/a-railroad-of-cells/
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Geometry-driven migration efficiency of autonomous epithelial cell clusters
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 20
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '18446'
abstract:
- lang: eng
  text: How living systems achieve precision in form and function despite their intrinsic
    stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps
    of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these
    morphomaps revealed that although blastomere divisions desynchronized passively,
    8-cell embryos converged toward robust three-dimensional shapes. Using topological
    analysis and genetic perturbations, we found that embryos progressively changed
    their cellular connectivity to a preferred topology, which could be predicted
    by a physical model in which actomyosin contractility and noise facilitate topological
    transitions, lowering surface energy. This mechanism favored regular embryo packing
    and promoted a higher number of inner cells in the 16-cell embryo. Synchronized
    division reduced embryo packing and generated substantially more misallocated
    cells and fewer inner-cell–mass cells. These findings suggest that stochasticity
    in division timing contributes to robust patterning.
acknowledgement: "We are grateful to the members of the Hiiragi laboratory for discussions
  and comments on the manuscript: R. Bloehs, S. Friese, S. Hozeifi, L. Pérez, and
  W. Schwarzer for their technical support; V. Janssen for establishing the PAB protocol;
  members of the Tsukiyama group for the animal care with monkeys, in particular H.
  Tsuchiya and M. Nakaya; Unité Commune d’Expérimentation Animale (UCEA, Jouy-en-Josas,
  France) for the animal care with rabbits; the EMBL electronic and mechanical workshops
  and the EMBL animal facility for their support; We thank Luxendo for the close collaboration
  in developing the light-sheet microscopy for mammalian embryos.\r\nFunding: This
  work was funded by the following: EMBL Interdisciplinary Postdoc Program (EIPOD)
  under Marie Sklodowska Curie Actions COFUND III RTD (to D.F.); JSPS Overseas Research
  Fellowship (to T.I.); Field of excellence “Complexity of life in basic research
  and innovation” of the University of Graz (to B.C.M.); European Research Council,
  ERC Advanced Grant “SelforganisingEmbryo”, grant agreement 742732; ERC Advanced
  Grant “COORDINATION” grant agreement 101055287 (to T.H.); Stichting LSH-TKI, grant
  LSHM21020 (to T.H.) JSPS KAKENHI grants JP21H05038 and JP22H05166 (to T.H.)"
article_number: eadh1145
article_processing_charge: No
article_type: original
author:
- first_name: Dimitri
  full_name: Fabrèges, Dimitri
  last_name: Fabrèges
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Prachiti
  full_name: Moghe, Prachiti
  last_name: Moghe
- first_name: Alison
  full_name: Kickuth, Alison
  last_name: Kickuth
- first_name: Takafumi
  full_name: Ichikawa, Takafumi
  last_name: Ichikawa
- first_name: Chizuru
  full_name: Iwatani, Chizuru
  last_name: Iwatani
- first_name: Tomoyuki
  full_name: Tsukiyama, Tomoyuki
  last_name: Tsukiyama
- first_name: Nathalie
  full_name: Daniel, Nathalie
  last_name: Daniel
- first_name: Julie
  full_name: Gering, Julie
  last_name: Gering
- first_name: Anniek
  full_name: Stokkermans, Anniek
  last_name: Stokkermans
- first_name: Adrian
  full_name: Wolny, Adrian
  last_name: Wolny
- first_name: Anna
  full_name: Kreshuk, Anna
  last_name: Kreshuk
- first_name: Véronique
  full_name: Duranthon, Véronique
  last_name: Duranthon
- first_name: Virginie
  full_name: Uhlman, Virginie
  last_name: Uhlman
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Takashi
  full_name: Hiiragi, Takashi
  last_name: Hiiragi
citation:
  ama: Fabrèges D, Corominas-Murtra B, Moghe P, et al. Temporal variability and cell
    mechanics control robustness in mammalian embryogenesis. <i>Science</i>. 2024;386(6718).
    doi:<a href="https://doi.org/10.1126/science.adh1145">10.1126/science.adh1145</a>
  apa: Fabrèges, D., Corominas-Murtra, B., Moghe, P., Kickuth, A., Ichikawa, T., Iwatani,
    C., … Hiiragi, T. (2024). Temporal variability and cell mechanics control robustness
    in mammalian embryogenesis. <i>Science</i>. AAAS. <a href="https://doi.org/10.1126/science.adh1145">https://doi.org/10.1126/science.adh1145</a>
  chicago: Fabrèges, Dimitri, Bernat Corominas-Murtra, Prachiti Moghe, Alison Kickuth,
    Takafumi Ichikawa, Chizuru Iwatani, Tomoyuki Tsukiyama, et al. “Temporal Variability
    and Cell Mechanics Control Robustness in Mammalian Embryogenesis.” <i>Science</i>.
    AAAS, 2024. <a href="https://doi.org/10.1126/science.adh1145">https://doi.org/10.1126/science.adh1145</a>.
  ieee: D. Fabrèges <i>et al.</i>, “Temporal variability and cell mechanics control
    robustness in mammalian embryogenesis,” <i>Science</i>, vol. 386, no. 6718. AAAS,
    2024.
  ista: Fabrèges D, Corominas-Murtra B, Moghe P, Kickuth A, Ichikawa T, Iwatani C,
    Tsukiyama T, Daniel N, Gering J, Stokkermans A, Wolny A, Kreshuk A, Duranthon
    V, Uhlman V, Hannezo EB, Hiiragi T. 2024. Temporal variability and cell mechanics
    control robustness in mammalian embryogenesis. Science. 386(6718), eadh1145.
  mla: Fabrèges, Dimitri, et al. “Temporal Variability and Cell Mechanics Control
    Robustness in Mammalian Embryogenesis.” <i>Science</i>, vol. 386, no. 6718, eadh1145,
    AAAS, 2024, doi:<a href="https://doi.org/10.1126/science.adh1145">10.1126/science.adh1145</a>.
  short: D. Fabrèges, B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani,
    T. Tsukiyama, N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon,
    V. Uhlman, E.B. Hannezo, T. Hiiragi, Science 386 (2024).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "All original code and data reported in this paper is publicly
  available as of the date of publication on Zenodo (124).\r\n124\r\nD. Fabrèges,
  B. Corominas-Murtra, P. Moghe, A. Kickuth, T. Ichikawa, C. Iwatani, T. Tsukiyama,
  N. Daniel, J. Gering, A. Stokkermans, A. Wolny, A. Kreshuk, V. Duranthon, V. Uhlmann,
  E. Hannezo, T. Hiiragi, Temporal variability and cell mechanics control robustness
  in mammalian embryogenesis, version 1.0, Zenodo (2024); https://doi.org/10.5281/ZENODO.12819781."
date_created: 2024-10-20T22:02:06Z
date_published: 2024-10-11T00:00:00Z
date_updated: 2026-10-01T10:54:32Z
day: '11'
department:
- _id: EdHa
doi: 10.1126/science.adh1145
external_id:
  isi:
  - '001422132300018'
  pmid:
  - '39388574'
fulldoi: https://doi.org/10.1126/science.adh1145
intvolume: '       386'
isi: 1
issue: '6718'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://hal.inrae.fr/hal-04447081v1/file/2023.01.24.525420.full.pdf
month: '10'
oa: 1
oa_version: Submitted Version
pmid: 1
publication: Science
publication_identifier:
  eissn:
  - 1095-9203
publication_status: published
publisher: AAAS
quality_controlled: '1'
related_material:
  record:
  - id: '23023'
    relation: research_data
    status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Temporal variability and cell mechanics control robustness in mammalian embryogenesis
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 386
year: '2024'
...
---
_id: '18071'
abstract:
- lang: eng
  text: Recent advancements on DAG-based consensus protocols allow for blockchains
    with improved metrics and properties, such as throughput and censorship-resistance.
    Variants of the Bullshark [18] consensus protocol are adopted for practical use
    by the Sui blockchain, for improved latency. However, the protocol is leader-based,
    and is strongly affected by crashed leaders that can lead to various performance
    issues, for example, decreased transaction throughput. In this paper, we propose
    HammerHead, a DAG-based consensus protocol, that is inspired by Carousel [8] and
    provides Leader-Utilization. Our proposal differs from Carousel, which is built
    for a chained consensus protocol; in HammerHead chain quality is inherited by
    the DAG. HammerHead needs to preserve safety and liveness, despite validators
    committing leader vertices asynchronously. The key idea is to update leader schedules
    dynamically, based on the validators' scores during the previous schedule. We
    implement HammerHead and show a minor improvement in performance for cases without
    faults. The major improvements in comparison to Bullshark appear in faulty settings.
    Specifically, we show a drastic, 2x-latency improvement and up to 40% increased
    throughput when crash faults occur (100 validators, 33 faults).
acknowledgement: This work is supported by Mysten Labs. We thank the Mysten Labs Engineering
  teams for valuable feedback broadly, and specifically to Laura Makdah for helping
  implementing the early reputation score system for validators and Dmitry Perelman
  for managing the overall implementation effort.
article_processing_charge: No
arxiv: 1
author:
- first_name: Giorgos
  full_name: Tsimos, Giorgos
  last_name: Tsimos
- first_name: Anastasios
  full_name: Kichidis, Anastasios
  last_name: Kichidis
- first_name: Alberto
  full_name: Sonnino, Alberto
  last_name: Sonnino
- first_name: Eleftherios
  full_name: Kokoris Kogias, Eleftherios
  id: f5983044-d7ef-11ea-ac6d-fd1430a26d30
  last_name: Kokoris Kogias
  orcid: 0000-0002-8827-3382
citation:
  ama: 'Tsimos G, Kichidis A, Sonnino A, Kokoris Kogias E. HammerHead: Leader reputation
    for dynamic scheduling. In: <i>Proceedings - International Conference on Distributed
    Computing Systems</i>. IEEE; 2024:1377-1387. doi:<a href="https://doi.org/10.1109/ICDCS60910.2024.00129">10.1109/ICDCS60910.2024.00129</a>'
  apa: 'Tsimos, G., Kichidis, A., Sonnino, A., &#38; Kokoris Kogias, E. (2024). HammerHead:
    Leader reputation for dynamic scheduling. In <i>Proceedings - International Conference
    on Distributed Computing Systems</i> (pp. 1377–1387). Jersey City, NJ, United
    States: IEEE. <a href="https://doi.org/10.1109/ICDCS60910.2024.00129">https://doi.org/10.1109/ICDCS60910.2024.00129</a>'
  chicago: 'Tsimos, Giorgos, Anastasios Kichidis, Alberto Sonnino, and Eleftherios
    Kokoris Kogias. “HammerHead: Leader Reputation for Dynamic Scheduling.” In <i>Proceedings
    - International Conference on Distributed Computing Systems</i>, 1377–87. IEEE,
    2024. <a href="https://doi.org/10.1109/ICDCS60910.2024.00129">https://doi.org/10.1109/ICDCS60910.2024.00129</a>.'
  ieee: 'G. Tsimos, A. Kichidis, A. Sonnino, and E. Kokoris Kogias, “HammerHead: Leader
    reputation for dynamic scheduling,” in <i>Proceedings - International Conference
    on Distributed Computing Systems</i>, Jersey City, NJ, United States, 2024, pp.
    1377–1387.'
  ista: 'Tsimos G, Kichidis A, Sonnino A, Kokoris Kogias E. 2024. HammerHead: Leader
    reputation for dynamic scheduling. Proceedings - International Conference on Distributed
    Computing Systems. ICDCS: International Conference on Distributed Computing Systems,
    1377–1387.'
  mla: 'Tsimos, Giorgos, et al. “HammerHead: Leader Reputation for Dynamic Scheduling.”
    <i>Proceedings - International Conference on Distributed Computing Systems</i>,
    IEEE, 2024, pp. 1377–87, doi:<a href="https://doi.org/10.1109/ICDCS60910.2024.00129">10.1109/ICDCS60910.2024.00129</a>.'
  short: G. Tsimos, A. Kichidis, A. Sonnino, E. Kokoris Kogias, in:, Proceedings -
    International Conference on Distributed Computing Systems, IEEE, 2024, pp. 1377–1387.
conference:
  end_date: 2024-07-26
  location: Jersey City, NJ, United States
  name: 'ICDCS: International Conference on Distributed Computing Systems'
  start_date: 2024-07-23
das_tickbox: '0'
date_created: 2024-09-15T22:01:41Z
date_published: 2024-07-26T00:00:00Z
date_updated: 2026-10-01T11:04:17Z
day: '26'
department:
- _id: ElKo
doi: 10.1109/ICDCS60910.2024.00129
external_id:
  arxiv:
  - '2309.12713'
  isi:
  - '001304430200120'
fulldoi: https://doi.org/10.1109/ICDCS60910.2024.00129
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://arxiv.org/abs/2309.12713
month: '07'
oa: 1
oa_version: Preprint
page: 1377-1387
publication: Proceedings - International Conference on Distributed Computing Systems
publication_identifier:
  eissn:
  - 2575-8411
  isbn:
  - '9798350386059'
  issn:
  - 1063-6927
publication_status: published
publisher: IEEE
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: 'HammerHead: Leader reputation for dynamic scheduling'
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '17284'
abstract:
- lang: eng
  text: Platelet homeostasis is essential for vascular integrity and immune defence1,2.
    Although the process of platelet formation by fragmenting megakaryocytes (MKs;
    thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms
    required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis)
    remains unclear3,4. Here we use intravital imaging to track the cellular dynamics
    of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs)
    as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver
    IFNα to the MK niche triggering local on-demand proliferation and maturation of
    MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet
    homeostasis at steady state and under stress. pDCs are best known for their ability
    to function as vigilant detectors of viral infection5. We show that virus-induced
    activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis.
    Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis.
    Together, we identify a pDC-dependent homeostatic circuit that involves innate
    immune sensing and demand-adapted release of inflammatory mediators to maintain
    homeostasis of the megakaryocytic lineage.
acknowledgement: 'We thank S. Helmer, N. Blount, E. Raatz and Z. Sisic for technical
  assistance. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German
  Research Foundation) SFB 1123 (S.M. project B06); SFB 914 (S.M. projects B02 and
  Z01, H.I.-A. project Z01, S.S. project A06, K.S. project B02, C. Schulz project
  A10, B.W. project A02, C. Scheiermann project B09); SFB 1054 (T.B. project B03);
  FOR2033 (F.G., R.A.J.O., S.M.); Individual research grant project ID: 514478744
  (F.G.); Heisenberg Programme project ID: 514477451 (F.G.); the DZHK (German Center
  for Cardiovascular Research) (MHA 1.4VD (S.M.), Postdoc Start-up Grant, 81×3600213
  (F.G.)); and LMUexcellence NFF (F.G.). W.F. received funding from China Scholarship
  Council (CSC, no. 201306270012). P.B. is supported by the German Research Foundation
  (DFG, project IDs 322900939, 432698239 and 445703531), European Research Council
  (ERC Consolidator grant no. 101001791) and the Federal Ministry of Education and
  Research (BMBF, STOP-FSGS-01GM2202C and NATON within the framework of the Network
  of University Medicine, no. 01KX2121). S.v.S. is supported by the START-Program
  of the Faculty of Medicine of the RWTH Aachen University (AZ 125/17). A.D. and S.E.
  are supported by the German Research Foundation (SFB TRR 267); S.E. by the BMBF
  in the framework of the Cluster4future program (CNATM—Cluster for Nucleic Acid Therapeutics
  Munich). This project has received funding from the European Research Council (ERC)
  under the European Union’s Horizon 2020 research and innovation programme (grant
  agreement no. 833440 to S.M.). F.G. received funding from the European Union’s Horizon
  2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement
  no. 747687. The project is funded by the European Union (ERC, MEKanics, 101078110).
  Views and opinions expressed are those of the author(s) only and do not necessarily
  reflect those of the European Union or the European Research Council Executive Agency.
  Neither the European Union nor the granting authority can be held responsible for
  them.'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Florian R
  full_name: Gärtner, Florian R
  id: 397A88EE-F248-11E8-B48F-1D18A9856A87
  last_name: Gärtner
  orcid: 0000-0001-6120-3723
- first_name: Hellen
  full_name: Ishikawa-Ankerhold, Hellen
  last_name: Ishikawa-Ankerhold
- first_name: Susanne
  full_name: Stutte, Susanne
  last_name: Stutte
- first_name: Wenwen
  full_name: Fu, Wenwen
  last_name: Fu
- first_name: Jutta
  full_name: Weitz, Jutta
  last_name: Weitz
- first_name: Anne
  full_name: Dueck, Anne
  last_name: Dueck
- first_name: Bhavishya
  full_name: Nelakuditi, Bhavishya
  last_name: Nelakuditi
- first_name: Valeria
  full_name: Fumagalli, Valeria
  last_name: Fumagalli
- first_name: Dominic
  full_name: Van Den Heuvel, Dominic
  last_name: Van Den Heuvel
- first_name: Larissa
  full_name: Belz, Larissa
  last_name: Belz
- first_name: Gulnoza
  full_name: Sobirova, Gulnoza
  last_name: Sobirova
- first_name: Zhe
  full_name: Zhang, Zhe
  last_name: Zhang
- first_name: Anna
  full_name: Titova, Anna
  last_name: Titova
- first_name: Alejandro Martinez
  full_name: Navarro, Alejandro Martinez
  last_name: Navarro
- first_name: Kami
  full_name: Pekayvaz, Kami
  last_name: Pekayvaz
- first_name: Michael
  full_name: Lorenz, Michael
  last_name: Lorenz
- first_name: Louisa
  full_name: Von Baumgarten, Louisa
  last_name: Von Baumgarten
- first_name: Jan
  full_name: Kranich, Jan
  last_name: Kranich
- first_name: Tobias
  full_name: Straub, Tobias
  last_name: Straub
- first_name: Bastian
  full_name: Popper, Bastian
  last_name: Popper
- first_name: Vanessa
  full_name: Zheden, Vanessa
  id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
  last_name: Zheden
  orcid: 0000-0002-9438-4783
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Chenglong
  full_name: Guo, Chenglong
  last_name: Guo
- first_name: Guido
  full_name: Piontek, Guido
  last_name: Piontek
- first_name: Saskia
  full_name: Von Stillfried, Saskia
  last_name: Von Stillfried
- first_name: Peter
  full_name: Boor, Peter
  last_name: Boor
- first_name: Marco
  full_name: Colonna, Marco
  last_name: Colonna
- first_name: Sebastian
  full_name: Clauß, Sebastian
  last_name: Clauß
- first_name: Christian
  full_name: Schulz, Christian
  last_name: Schulz
- first_name: Thomas
  full_name: Brocker, Thomas
  last_name: Brocker
- first_name: Barbara
  full_name: Walzog, Barbara
  last_name: Walzog
- first_name: Christoph
  full_name: Scheiermann, Christoph
  last_name: Scheiermann
- first_name: William C.
  full_name: Aird, William C.
  last_name: Aird
- first_name: Claus
  full_name: Nerlov, Claus
  last_name: Nerlov
- first_name: Konstantin
  full_name: Stark, Konstantin
  last_name: Stark
- first_name: Tobias
  full_name: Petzold, Tobias
  last_name: Petzold
- first_name: Stefan
  full_name: Engelhardt, Stefan
  last_name: Engelhardt
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Martina
  full_name: Rudelius, Martina
  last_name: Rudelius
- first_name: Robert A.J.
  full_name: Oostendorp, Robert A.J.
  last_name: Oostendorp
- first_name: Matteo
  full_name: Iannacone, Matteo
  last_name: Iannacone
- first_name: Matthias
  full_name: Heinig, Matthias
  last_name: Heinig
- first_name: Steffen
  full_name: Massberg, Steffen
  last_name: Massberg
citation:
  ama: Gärtner FR, Ishikawa-Ankerhold H, Stutte S, et al. Plasmacytoid dendritic cells
    control homeostasis of megakaryopoiesis. <i>Nature</i>. 2024;631:645-653. doi:<a
    href="https://doi.org/10.1038/s41586-024-07671-y">10.1038/s41586-024-07671-y</a>
  apa: Gärtner, F. R., Ishikawa-Ankerhold, H., Stutte, S., Fu, W., Weitz, J., Dueck,
    A., … Massberg, S. (2024). Plasmacytoid dendritic cells control homeostasis of
    megakaryopoiesis. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-024-07671-y">https://doi.org/10.1038/s41586-024-07671-y</a>
  chicago: Gärtner, Florian R, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu,
    Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, et al. “Plasmacytoid Dendritic
    Cells Control Homeostasis of Megakaryopoiesis.” <i>Nature</i>. Springer Nature,
    2024. <a href="https://doi.org/10.1038/s41586-024-07671-y">https://doi.org/10.1038/s41586-024-07671-y</a>.
  ieee: F. R. Gärtner <i>et al.</i>, “Plasmacytoid dendritic cells control homeostasis
    of megakaryopoiesis,” <i>Nature</i>, vol. 631. Springer Nature, pp. 645–653, 2024.
  ista: Gärtner FR, Ishikawa-Ankerhold H, Stutte S, Fu W, Weitz J, Dueck A, Nelakuditi
    B, Fumagalli V, Van Den Heuvel D, Belz L, Sobirova G, Zhang Z, Titova A, Navarro
    AM, Pekayvaz K, Lorenz M, Von Baumgarten L, Kranich J, Straub T, Popper B, Zheden
    V, Kaufmann W, Guo C, Piontek G, Von Stillfried S, Boor P, Colonna M, Clauß S,
    Schulz C, Brocker T, Walzog B, Scheiermann C, Aird WC, Nerlov C, Stark K, Petzold
    T, Engelhardt S, Sixt MK, Hauschild R, Rudelius M, Oostendorp RAJ, Iannacone M,
    Heinig M, Massberg S. 2024. Plasmacytoid dendritic cells control homeostasis of
    megakaryopoiesis. Nature. 631, 645–653.
  mla: Gärtner, Florian R., et al. “Plasmacytoid Dendritic Cells Control Homeostasis
    of Megakaryopoiesis.” <i>Nature</i>, vol. 631, Springer Nature, 2024, pp. 645–53,
    doi:<a href="https://doi.org/10.1038/s41586-024-07671-y">10.1038/s41586-024-07671-y</a>.
  short: F.R. Gärtner, H. Ishikawa-Ankerhold, S. Stutte, W. Fu, J. Weitz, A. Dueck,
    B. Nelakuditi, V. Fumagalli, D. Van Den Heuvel, L. Belz, G. Sobirova, Z. Zhang,
    A. Titova, A.M. Navarro, K. Pekayvaz, M. Lorenz, L. Von Baumgarten, J. Kranich,
    T. Straub, B. Popper, V. Zheden, W. Kaufmann, C. Guo, G. Piontek, S. Von Stillfried,
    P. Boor, M. Colonna, S. Clauß, C. Schulz, T. Brocker, B. Walzog, C. Scheiermann,
    W.C. Aird, C. Nerlov, K. Stark, T. Petzold, S. Engelhardt, M.K. Sixt, R. Hauschild,
    M. Rudelius, R.A.J. Oostendorp, M. Iannacone, M. Heinig, S. Massberg, Nature 631
    (2024) 645–653.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Imaging and flow cytometry raw data are available on request.
  scRNA-seq data are accessible at the GEO (GSE261996). Bulk RNA-seq data are accessible
  at the GEO (GSE185488). Source data are provided with this paper.
date_created: 2024-07-21T22:01:02Z
date_published: 2024-07-18T00:00:00Z
date_updated: 2026-10-01T11:17:11Z
day: '18'
ddc:
- '570'
department:
- _id: EM-Fac
- _id: MiSi
- _id: Bio
doi: 10.1038/s41586-024-07671-y
ec_funded: 1
external_id:
  isi:
  - '001281636500020'
  pmid:
  - '38987596'
file:
- access_level: open_access
  checksum: aa004afc72d2489f0fb0fcbc9919fbbd
  content_type: application/pdf
  creator: dernst
  date_created: 2024-07-22T06:16:11Z
  date_updated: 2024-07-22T06:16:11Z
  file_id: '17286'
  file_name: 2024_Nature_Gaertner.pdf
  file_size: 15704819
  relation: main_file
  success: 1
file_date_updated: 2024-07-22T06:16:11Z
fulldoi: https://doi.org/10.1038/s41586-024-07671-y
has_accepted_license: '1'
intvolume: '       631'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 645-653
pmid: 1
project:
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '747687'
  name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/heiniglab/gaertner_megakaryocytes
researchdata_availability: upon request
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 631
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18920'
abstract:
- lang: eng
  text: The globally distributed marine alga Emiliania huxleyi has cooling effect
    on the Earth’s climate. The population density of E. huxleyi is restricted by
    Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite
    the impact of E. huxleyi viruses on the climate, there is limited information
    about their structure and replication. Here, we show that the dsDNA genome inside
    the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane.
    EhV-201 virions infect E. huxleyi by using fivefold vertices to bind to and fuse
    the virus’ inner membrane with the cell plasma membrane. Progeny virions assemble
    in the cytoplasm at the surface of endoplasmic reticulum–derived membrane segments.
    Genome packaging initiates synchronously with the capsid assembly and completes
    through an aperture in the forming capsid. The genome-filled capsids acquire an
    outer membrane by budding into intracellular vesicles. EhV-201 infection induces
    a loss of surface protective layers from E. huxleyi cells, which enables the continuous
    release of virions by exocytosis.
acknowledgement: We acknowledge (i) the Cryo-Electron Microscopy and Tomography Core
  Facility and Proteomics Core Facility of the Central European Institute of Technology
  (CEITEC), Masaryk University, supported by the Ministry of Education, Youth, and
  Sports of the Czech Republic (grant LM2018127); (ii) the Cellular Imaging Core Facility
  supported by the Czech-BioImaging large RI project (LM2018129 funded by MEYS CR);
  and (iii) Plant Sciences Core Facility for support with obtaining scientific data
  presented here. We acknowledge support from the project National Institute of Virology
  and Bacteriology (Program EXCELES, ID project no. LX22NPO5103), funded by the European
  Union - Next Generation EU. This work received funding from the Czech Science Foundation
  grant GX 19-259882X to P.P., from European Regional Development Fund-Project “MSCAfellow2@MUNI”
  (no. CZ.02.2.69/0.0/0.0/18_070/0009846) to C.R.B., and from Brno PhD talent scholarship
  funded by Brno city municipality to M.H.
article_number: 'eadk1954 '
article_processing_charge: Yes
article_type: original
author:
- first_name: Miroslav
  full_name: Homola, Miroslav
  last_name: Homola
- first_name: Renate Carina
  full_name: Büttner, Renate Carina
  id: 3b7984c9-17ff-11ed-b6fe-f943c4a5b626
  last_name: Büttner
- first_name: Tibor
  full_name: Füzik, Tibor
  last_name: Füzik
- first_name: Pavel
  full_name: Křepelka, Pavel
  last_name: Křepelka
- first_name: Radka
  full_name: Holbová, Radka
  last_name: Holbová
- first_name: Jiří
  full_name: Nováček, Jiří
  last_name: Nováček
- first_name: Marten L.
  full_name: Chaillet, Marten L.
  last_name: Chaillet
- first_name: Jakub
  full_name: Žák, Jakub
  last_name: Žák
- first_name: Danyil
  full_name: Grybchuk, Danyil
  last_name: Grybchuk
- first_name: Friedrich
  full_name: Förster, Friedrich
  last_name: Förster
- first_name: William H.
  full_name: Wilson, William H.
  last_name: Wilson
- first_name: Declan C.
  full_name: Schroeder, Declan C.
  last_name: Schroeder
- first_name: Pavel
  full_name: Plevka, Pavel
  last_name: Plevka
citation:
  ama: Homola M, Büttner RC, Füzik T, et al. Structure and replication cycle of a
    virus infecting climate-modulating alga Emiliania huxleyi. <i>Science Advances</i>.
    2024;10(15). doi:<a href="https://doi.org/10.1126/sciadv.adk1954">10.1126/sciadv.adk1954</a>
  apa: Homola, M., Büttner, R. C., Füzik, T., Křepelka, P., Holbová, R., Nováček,
    J., … Plevka, P. (2024). Structure and replication cycle of a virus infecting
    climate-modulating alga Emiliania huxleyi. <i>Science Advances</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.adk1954">https://doi.org/10.1126/sciadv.adk1954</a>
  chicago: Homola, Miroslav, Renate Carina Büttner, Tibor Füzik, Pavel Křepelka, Radka
    Holbová, Jiří Nováček, Marten L. Chaillet, et al. “Structure and Replication Cycle
    of a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” <i>Science Advances</i>.
    American Association for the Advancement of Science, 2024. <a href="https://doi.org/10.1126/sciadv.adk1954">https://doi.org/10.1126/sciadv.adk1954</a>.
  ieee: M. Homola <i>et al.</i>, “Structure and replication cycle of a virus infecting
    climate-modulating alga Emiliania huxleyi,” <i>Science Advances</i>, vol. 10,
    no. 15. American Association for the Advancement of Science, 2024.
  ista: Homola M, Büttner RC, Füzik T, Křepelka P, Holbová R, Nováček J, Chaillet
    ML, Žák J, Grybchuk D, Förster F, Wilson WH, Schroeder DC, Plevka P. 2024. Structure
    and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi.
    Science Advances. 10(15), eadk1954.
  mla: Homola, Miroslav, et al. “Structure and Replication Cycle of a Virus Infecting
    Climate-Modulating Alga Emiliania Huxleyi.” <i>Science Advances</i>, vol. 10,
    no. 15, eadk1954, American Association for the Advancement of Science, 2024, doi:<a
    href="https://doi.org/10.1126/sciadv.adk1954">10.1126/sciadv.adk1954</a>.
  short: M. Homola, R.C. Büttner, T. Füzik, P. Křepelka, R. Holbová, J. Nováček, M.L.
    Chaillet, J. Žák, D. Grybchuk, F. Förster, W.H. Wilson, D.C. Schroeder, P. Plevka,
    Science Advances 10 (2024).
das_tickbox: '1'
dataavailabilitystatement: 'Cryo-EM maps and structure coordinates were deposited
  to the Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB), respectively,
  with the following accession numbers: (i) EhV-201 virion vertex reconstructed using
  a single-particle approach and a mask with the diameter of 50 nm (EMD-17650); (ii)
  EhV-201 virion vertex reconstructed using sub-tomogram averaging and a mask with
  the diameter of 50 nm (EMD-17649); (iii) EhV-201 virion vertex reconstructed using
  sub-tomogram averaging and a mask with the diameter of 50 nm and a mask covering
  only the capsid layer (EMD-19036) and the fitted structure of AlphaFold2 predicted
  EhV-201 major capsid protein and penton protein (PDB 8RBT); (iv) EhV-201 virion
  vertex reconstructed by sub-tomogram averaging and a mask with the diameter of 120
  nm (EMD-17651); and (v) composite map of the EhV201 virion (EMD-19035) and corresponding
  structure of icosahedral asymmetric unit (PDB 8RBS). All custom scripts used during
  tomographic reconstruction have been made available at https://github.com/fuzikt/tomostarpy.
  Additional files have been made available at https://doi.org/10.5061/dryad.p5hqbzkw0:
  (i) cryo-ET tilt series of lamellas of control and EhV-201 infected E. huxleyi cells;
  (ii) segmentations of cryo-tomograms of infected and control cells; (iii) block
  face imaging data series of high-pressure frozen and resin-embedded E. huxleyi infected
  by EhV-201; (iv) scripts used during tomographic reconstruction; (v) fluorescence
  microscopy images of E. huxleyi infected by EhV-201; and (vi) mass spectrometry
  report of EhV-201 virion protein composition. Cryo-ET tilt series used for EhV-201
  virion structure determination were deposited to EMPIAR and linked to the file EMD-17649.
  All other data needed to evaluate the conclusions in the paper are present in the
  paper and/or the Supplementary Materials.'
date_created: 2025-01-27T14:32:34Z
date_published: 2024-04-01T00:00:00Z
date_updated: 2026-10-01T11:15:30Z
day: '01'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.1126/sciadv.adk1954
external_id:
  pmid:
  - '38598627'
file:
- access_level: open_access
  checksum: 291dd7ceccbe6bfd8e0a9157584f88e9
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  creator: dernst
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  date_updated: 2025-01-27T14:40:08Z
  file_id: '18921'
  file_name: 2024_ScienceAdv_Homola.pdf
  file_size: 40623405
  relation: main_file
  success: 1
file_date_updated: 2025-01-27T14:40:08Z
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has_accepted_license: '1'
intvolume: '        10'
issue: '15'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: ' https://github.com/fuzikt/tomostarpy.'
  record:
  - id: '23025'
    relation: research_data
    status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Structure and replication cycle of a virus infecting climate-modulating alga
  Emiliania huxleyi
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 10
year: '2024'
...
---
_id: '18052'
abstract:
- lang: eng
  text: Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL)
    is an electron microscope (EM) sample preparation technique which allows for high-resolution
    visualization of membrane proteins with high sensitivity. However, image acquisition
    of specific replica profiles such as synapses in a large field of EM view needs
    a valid experience and a long time for manual searching. Here, we describe how
    to utilize deep learning for automatizing image acquisition of specific profiles
    of interest in replica samples. This protocol facilitates the labor-intensive
    collection of EM images, in particular for rare profiles. We provide instructions
    for using SerialEM image acquisition software in conjunction with object detection
    by our newly developed deep learning software DarEM, to automatically acquire
    tilt series of all synapses in a selected region. We then show how to perform
    a mostly automated analysis of gold particle labeling in the acquired images by
    utilizing Darea software.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: This research was supported by the European Research Council Advanced
  Grant 694539 to RS and by the Scientific Service Units of IST Austria through resources
  provided by the Electron Microscopy Facility.
alternative_title:
- Neuromethods
article_processing_charge: No
author:
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Tommaso
  full_name: Costanzo, Tommaso
  id: D93824F4-D9BA-11E9-BB12-F207E6697425
  last_name: Costanzo
  orcid: 0000-0001-9732-3815
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: 'Kleindienst D, Costanzo T, Shigemoto R. Automated Imaging and Analysis of
    Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: Lübke JHR,
    Rollenhagen A, eds. <i>New Aspects in Analyzing the Synaptic Organization of the
    Brain</i>. 1st ed. New York: Springer Nature; 2024:123-137. doi:<a href="https://doi.org/10.1007/978-1-0716-4019-7_8">10.1007/978-1-0716-4019-7_8</a>'
  apa: 'Kleindienst, D., Costanzo, T., &#38; Shigemoto, R. (2024). Automated Imaging
    and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning.
    In J. H. R. Lübke &#38; A. Rollenhagen (Eds.), <i>New Aspects in Analyzing the
    Synaptic Organization of the Brain</i> (1st ed., pp. 123–137). New York: Springer
    Nature. <a href="https://doi.org/10.1007/978-1-0716-4019-7_8">https://doi.org/10.1007/978-1-0716-4019-7_8</a>'
  chicago: 'Kleindienst, David, Tommaso Costanzo, and Ryuichi Shigemoto. “Automated
    Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep
    Learning.” In <i>New Aspects in Analyzing the Synaptic Organization of the Brain</i>,
    edited by Joachim H.R.  Lübke and Astrid Rollenhagen, 1st ed., 123–37. New York:
    Springer Nature, 2024. <a href="https://doi.org/10.1007/978-1-0716-4019-7_8">https://doi.org/10.1007/978-1-0716-4019-7_8</a>.'
  ieee: 'D. Kleindienst, T. Costanzo, and R. Shigemoto, “Automated Imaging and Analysis
    of Synapses in Freeze-Fracture Replica Samples with Deep Learning,” in <i>New
    Aspects in Analyzing the Synaptic Organization of the Brain</i>, 1st ed., J. H.
    R. Lübke and A. Rollenhagen, Eds. New York: Springer Nature, 2024, pp. 123–137.'
  ista: 'Kleindienst D, Costanzo T, Shigemoto R. 2024.Automated Imaging and Analysis
    of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: New Aspects
    in Analyzing the Synaptic Organization of the Brain. Neuromethods, , 123–137.'
  mla: Kleindienst, David, et al. “Automated Imaging and Analysis of Synapses in Freeze-Fracture
    Replica Samples with Deep Learning.” <i>New Aspects in Analyzing the Synaptic
    Organization of the Brain</i>, edited by Joachim H.R.  Lübke and Astrid Rollenhagen,
    1st ed., Springer Nature, 2024, pp. 123–37, doi:<a href="https://doi.org/10.1007/978-1-0716-4019-7_8">10.1007/978-1-0716-4019-7_8</a>.
  short: D. Kleindienst, T. Costanzo, R. Shigemoto, in:, J.H.R. Lübke, A. Rollenhagen
    (Eds.), New Aspects in Analyzing the Synaptic Organization of the Brain, 1st ed.,
    Springer Nature, New York, 2024, pp. 123–137.
corr_author: '1'
das_tickbox: '0'
date_created: 2024-09-10T12:32:38Z
date_published: 2024-08-27T00:00:00Z
date_updated: 2026-10-01T11:17:28Z
day: '27'
department:
- _id: EM-Fac
- _id: RySh
doi: 10.1007/978-1-0716-4019-7_8
ec_funded: 1
edition: '1'
editor:
- first_name: 'Joachim H.R. '
  full_name: 'Lübke, Joachim H.R. '
  last_name: Lübke
- first_name: Astrid
  full_name: Rollenhagen, Astrid
  last_name: Rollenhagen
fulldoi: https://doi.org/10.1007/978-1-0716-4019-7_8
language:
- iso: eng
month: '08'
oa_version: None
page: 123-137
place: New York
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
publication: New Aspects in Analyzing the Synaptic Organization of the Brain
publication_identifier:
  eisbn:
  - '9781071640197'
  eissn:
  - 1940-6045
  isbn:
  - '9781071640180'
  issn:
  - 0893-2336
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples
  with Deep Learning
type: book_chapter
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '14842'
abstract:
- lang: eng
  text: Eva Benkova received a PhD in Biophysics at the Institute of Biophysics of
    the Czech Academy of Sciences in 1998. After working as a postdoc at the Max Planck
    Institute in Cologne and the Center for Plant Molecular Biology (ZMBP) in Tübingen,
    she became a group leader at the Plant Systems Biology Department of the Vlaams
    Instituut voor Biotechnologie (VIB) in Gent. In 2012, she transitioned to an Assistant
    Professor position at the Institute of Science and Technology Austria (ISTA) where
    she was later promoted to Professor. Since 2021, she has served as the Dean of
    the ISTA Graduate School. As a plant developmental biologist, she focuses on unraveling
    the molecular mechanisms and principles that underlie hormonal interactions in
    plants. In her current work, she explores the intricate connections between hormones
    and regulatory pathways that mediate the perception of environmental stimuli,
    including abiotic stress and nitrate availability.
article_processing_charge: No
author:
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
citation:
  ama: Benková E. <i>Eva Benkova</i>. Vol 34. Elsevier; 2024:R3-R5. doi:<a href="https://doi.org/10.1016/j.cub.2023.11.039">10.1016/j.cub.2023.11.039</a>
  apa: Benková, E. (2024). <i>Eva Benkova</i>. <i>Current Biology</i> (Vol. 34, pp.
    R3–R5). Elsevier. <a href="https://doi.org/10.1016/j.cub.2023.11.039">https://doi.org/10.1016/j.cub.2023.11.039</a>
  chicago: Benková, Eva. <i>Eva Benkova</i>. <i>Current Biology</i>. Vol. 34. Elsevier,
    2024. <a href="https://doi.org/10.1016/j.cub.2023.11.039">https://doi.org/10.1016/j.cub.2023.11.039</a>.
  ieee: E. Benková, <i>Eva Benkova</i>, vol. 34, no. 1. Elsevier, 2024, pp. R3–R5.
  ista: Benková E. 2024. Eva Benkova, Elsevier,p.
  mla: Benková, Eva. “Eva Benkova.” <i>Current Biology</i>, vol. 34, no. 1, Elsevier,
    2024, pp. R3–5, doi:<a href="https://doi.org/10.1016/j.cub.2023.11.039">10.1016/j.cub.2023.11.039</a>.
  short: E. Benková, Eva Benkova, Elsevier, 2024.
corr_author: '1'
das_tickbox: '0'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-01-08T00:00:00Z
date_updated: 2026-10-01T11:17:58Z
day: '08'
ddc:
- '580'
department:
- _id: EvBe
doi: 10.1016/j.cub.2023.11.039
external_id:
  pmid:
  - '38194926'
fulldoi: https://doi.org/10.1016/j.cub.2023.11.039
intvolume: '        34'
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.cub.2023.11.039
month: '01'
oa: 1
oa_version: Published Version
page: R3-R5
pmid: 1
publication: Current Biology
publication_identifier:
  eissn:
  - 1879-0445
publication_status: published
publisher: Elsevier
quality_controlled: '1'
researchdata_availability: not applicable
status: public
supplementarymaterial: no
title: Eva Benkova
type: other_academic_publication
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 34
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '23025'
abstract:
- lang: eng
  text: The globally distributed marine alga Emiliania huxleyi produces reflective
    calcite disks (coccoliths) that increase the albedo of ocean water and thus reduce
    the heat absorption in the ocean, which cools the Earth’s climate. The population
    density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E.
    huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate,
    there is limited information about their structure and replication. Here we show
    that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane,
    capsid, and outer membrane decorated with numerous transmembrane proteins. The
    virions are prone to deformation, and parts of their capsids deviate from the
    icosahedral arrangement. EhV-201 virions infect E. huxleyi by using their fivefold
    vertex to bind to a host cell and fuse the virus’s inner membrane with the plasma
    membrane. Whereas the replication of EhV-201 probably occurs in the nucleus, virions
    assemble in the cytoplasm at the surface of endoplasmic reticulum-derived membrane
    segments. Genome packaging initiates synchronously with the capsid assembly and
    completes through an aperture in the forming capsid. Upon the completion of genome
    packaging, the capsids change conformation, which enables them to acquire an outer
    membrane by budding into intracellular vesicles. EhV-201 infection induces a loss
    of surface protective layers from E. huxleyi cells, which allows the continuous
    release of virions by exocytosis. Our results provide insight into how EhVs bypass
    the surface protective layers of E. huxleyi and exploit the organelles of an infected
    cell for progeny assembly.
article_processing_charge: No
author:
- first_name: Miroslav
  full_name: Homola, Miroslav
  last_name: Homola
- first_name: Carina
  full_name: Büttner, Carina
  last_name: Büttner
- first_name: Tibor
  full_name: Füzik, Tibor
  last_name: Füzik
- first_name: Pavel
  full_name: Krepelka, Pavel
  last_name: Krepelka
- first_name: Radka
  full_name: Holbová, Radka
  last_name: Holbová
- first_name: Marten
  full_name: Chaillet, Marten
  last_name: Chaillet
- first_name: Jiří
  full_name: Nováček, Jiří
  last_name: Nováček
- first_name: Friedrich
  full_name: Förster, Friedrich
  last_name: Förster
- first_name: William
  full_name: Wilson, William
  last_name: Wilson
- first_name: Declan
  full_name: Schroeder, Declan
  last_name: Schroeder
- first_name: Pavel
  full_name: Plevka, Pavel
  last_name: Plevka
citation:
  ama: 'Homola M, Büttner C, Füzik T, et al. Data: Structure and replication cycle
    of a virus infecting climate-modulating alga Emiliania huxleyi. 2024. doi:<a href="https://doi.org/10.5061/dryad.p5hqbzkw0">10.5061/dryad.p5hqbzkw0</a>'
  apa: 'Homola, M., Büttner, C., Füzik, T., Krepelka, P., Holbová, R., Chaillet, M.,
    … Plevka, P. (2024). Data: Structure and replication cycle of a virus infecting
    climate-modulating alga Emiliania huxleyi. Dryad. <a href="https://doi.org/10.5061/dryad.p5hqbzkw0">https://doi.org/10.5061/dryad.p5hqbzkw0</a>'
  chicago: 'Homola, Miroslav, Carina Büttner, Tibor Füzik, Pavel Krepelka, Radka Holbová,
    Marten Chaillet, Jiří Nováček, et al. “Data: Structure and Replication Cycle of
    a Virus Infecting Climate-Modulating Alga Emiliania Huxleyi.” Dryad, 2024. <a
    href="https://doi.org/10.5061/dryad.p5hqbzkw0">https://doi.org/10.5061/dryad.p5hqbzkw0</a>.'
  ieee: 'M. Homola <i>et al.</i>, “Data: Structure and replication cycle of a virus
    infecting climate-modulating alga Emiliania huxleyi.” Dryad, 2024.'
  ista: 'Homola M, Büttner C, Füzik T, Krepelka P, Holbová R, Chaillet M, Nováček
    J, Förster F, Wilson W, Schroeder D, Plevka P. 2024. Data: Structure and replication
    cycle of a virus infecting climate-modulating alga Emiliania huxleyi, Dryad, <a
    href="https://doi.org/10.5061/dryad.p5hqbzkw0">10.5061/dryad.p5hqbzkw0</a>.'
  mla: 'Homola, Miroslav, et al. <i>Data: Structure and Replication Cycle of a Virus
    Infecting Climate-Modulating Alga Emiliania Huxleyi</i>. Dryad, 2024, doi:<a href="https://doi.org/10.5061/dryad.p5hqbzkw0">10.5061/dryad.p5hqbzkw0</a>.'
  short: M. Homola, C. Büttner, T. Füzik, P. Krepelka, R. Holbová, M. Chaillet, J.
    Nováček, F. Förster, W. Wilson, D. Schroeder, P. Plevka, (2024).
date_created: 2026-10-01T11:13:02Z
date_published: 2024-02-07T00:00:00Z
date_updated: 2026-10-01T11:15:29Z
day: '07'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.5061/dryad.p5hqbzkw0
fulldoi: https://doi.org/10.5061/dryad.p5hqbzkw0
main_file_link:
- open_access: '1'
  url: https://doi.org/10.5061/dryad.p5hqbzkw0
month: '02'
oa: 1
oa_version: None
publisher: Dryad
related_material:
  record:
  - id: '18920'
    relation: used_in_publication
    status: public
status: public
title: 'Data: Structure and replication cycle of a virus infecting climate-modulating
  alga Emiliania huxleyi'
type: research_data_reference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '15146'
abstract:
- lang: eng
  text: The extracellular matrix (ECM) serves as a scaffold for cells and plays an
    essential role in regulating numerous cellular processes, including cell migration
    and proliferation. Due to limitations in specimen preparation for conventional
    room-temperature electron microscopy, we lack structural knowledge on how ECM
    components are secreted, remodeled, and interact with surrounding cells. We have
    developed a 3D-ECM platform compatible with sample thinning by cryo-focused ion
    beam milling, the lift-out extraction procedure, and cryo-electron tomography.
    Our workflow implements cell-derived matrices (CDMs) grown on EM grids, resulting
    in a versatile tool closely mimicking ECM environments. This allows us to visualize
    ECM for the first time in its hydrated, native context. Our data reveal an intricate
    network of extracellular fibers, their positioning relative to matrix-secreting
    cells, and previously unresolved structural entities. Our workflow and results
    add to the structural atlas of the ECM, providing novel insights into its secretion
    and assembly.
acknowledged_ssus:
- _id: LifeSc
- _id: ScienComp
- _id: EM-Fac
- _id: M-Shop
acknowledgement: "Open Access funding provided by IST Austria. We thank Armel Nicolas
  and his team at the ISTA proteomics facility, Alois Schloegl, Stefano Elefante,
  and colleagues at the ISTA Scientific Computing facility, Tommaso Constanzo and
  Ludek Lovicar at the Electron Microsocpy Facility (EMF), and Thomas Menner at the
  Miba Machine shop for their support. We also thank Wanda Kukulski (University of
  Bern) as well as Darío Porley, Andreas Thader, and other members of the Schur group
  for helpful discussions. Matt Swulius and Jessica Heebner provided great support
  in using Dragonfly. We thank Dorotea Fracciolla (Art & Science) for support in figure
  illustration.\r\n\r\nThis research was supported by the Scientific Service Units
  of ISTA through resources provided by Scientific Computing, the Lab Support Facility,
  and the Electron Microscopy Facility. We acknowledge funding support from the following
  sources: Austrian Science Fund (FWF) grant P33367 (to F.K.M. Schur), the Federation
  of European Biochemical Societies (to F.K.M. Schur), Niederösterreich (NÖ) Fonds
  (to B. Zens), FWF grant E435 (to J.M. Hansen), European Research Council under the
  European Union’s Horizon 2020 research (grant agreement No. 724373) (to M. Sixt),
  and Jenny and Antti Wihuri Foundation (to J. Alanko). This publication has been
  made possible in part by CZI grant DAF2021-234754 and grant DOI https://doi.org/10.37921/812628ebpcwg
  from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community
  Foundation (to F.K.M. Schur)."
article_number: e202309125
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Bettina
  full_name: Zens, Bettina
  id: 45FD126C-F248-11E8-B48F-1D18A9856A87
  last_name: Zens
  orcid: 0000-0002-9561-1239
- first_name: Florian
  full_name: Fäßler, Florian
  id: 404F5528-F248-11E8-B48F-1D18A9856A87
  last_name: Fäßler
  orcid: 0000-0001-7149-769X
- first_name: Jesse
  full_name: Hansen, Jesse
  id: 1063c618-6f9b-11ec-9123-f912fccded63
  last_name: Hansen
  orcid: 0000-0001-7967-2085
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Julia
  full_name: Datler, Julia
  id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
  last_name: Datler
  orcid: 0000-0002-3616-8580
- first_name: Victor-Valentin
  full_name: Hodirnau, Victor-Valentin
  id: 3661B498-F248-11E8-B48F-1D18A9856A87
  last_name: Hodirnau
  orcid: 0000-0003-3904-947X
- first_name: Vanessa
  full_name: Zheden, Vanessa
  id: 39C5A68A-F248-11E8-B48F-1D18A9856A87
  last_name: Zheden
  orcid: 0000-0002-9438-4783
- first_name: Jonna H
  full_name: Alanko, Jonna H
  id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
  last_name: Alanko
  orcid: 0000-0002-7698-3061
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
citation:
  ama: Zens B, Fäßler F, Hansen J, et al. Lift-out cryo-FIBSEM and cryo-ET reveal
    the ultrastructural landscape of extracellular matrix. <i>Journal of Cell Biology</i>.
    2024;223(6). doi:<a href="https://doi.org/10.1083/jcb.202309125">10.1083/jcb.202309125</a>
  apa: Zens, B., Fäßler, F., Hansen, J., Hauschild, R., Datler, J., Hodirnau, V.-V.,
    … Schur, F. K. (2024). Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural
    landscape of extracellular matrix. <i>Journal of Cell Biology</i>. Rockefeller
    University Press. <a href="https://doi.org/10.1083/jcb.202309125">https://doi.org/10.1083/jcb.202309125</a>
  chicago: Zens, Bettina, Florian Fäßler, Jesse Hansen, Robert Hauschild, Julia Datler,
    Victor-Valentin Hodirnau, Vanessa Zheden, Jonna H Alanko, Michael K Sixt, and
    Florian KM Schur. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural
    Landscape of Extracellular Matrix.” <i>Journal of Cell Biology</i>. Rockefeller
    University Press, 2024. <a href="https://doi.org/10.1083/jcb.202309125">https://doi.org/10.1083/jcb.202309125</a>.
  ieee: B. Zens <i>et al.</i>, “Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural
    landscape of extracellular matrix,” <i>Journal of Cell Biology</i>, vol. 223,
    no. 6. Rockefeller University Press, 2024.
  ista: Zens B, Fäßler F, Hansen J, Hauschild R, Datler J, Hodirnau V-V, Zheden V,
    Alanko JH, Sixt MK, Schur FK. 2024. Lift-out cryo-FIBSEM and cryo-ET reveal the
    ultrastructural landscape of extracellular matrix. Journal of Cell Biology. 223(6),
    e202309125.
  mla: Zens, Bettina, et al. “Lift-out Cryo-FIBSEM and Cryo-ET Reveal the Ultrastructural
    Landscape of Extracellular Matrix.” <i>Journal of Cell Biology</i>, vol. 223,
    no. 6, e202309125, Rockefeller University Press, 2024, doi:<a href="https://doi.org/10.1083/jcb.202309125">10.1083/jcb.202309125</a>.
  short: B. Zens, F. Fäßler, J. Hansen, R. Hauschild, J. Datler, V.-V. Hodirnau, V.
    Zheden, J.H. Alanko, M.K. Sixt, F.K. Schur, Journal of Cell Biology 223 (2024).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: 'Representative tomograms containing the data shown in
  Fig. 3, and Figs. S5 and S9 have been deposited in the Electron Microscopy Data
  Bank under accession codes: EMD-18490, EMD-18491, EMD-18492, EMD-18493, and EMD-18494.
  All tilt series, including frames, raw tilt series, and reconstructed IsoNet-filtered
  tomograms, were deposited in the Electron Microscopy Public Image Archive database
  under the accession code EMPIAR-11897.'
date_created: 2024-03-21T06:45:51Z
date_published: 2024-03-20T00:00:00Z
date_updated: 2026-10-01T11:24:27Z
day: '20'
ddc:
- '570'
department:
- _id: FlSc
- _id: MiSi
- _id: Bio
- _id: EM-Fac
doi: 10.1083/jcb.202309125
ec_funded: 1
external_id:
  isi:
  - '001264190100001'
  pmid:
  - '38506714'
file:
- access_level: open_access
  checksum: 90d1984a93660735e506c2a304bc3f73
  content_type: application/pdf
  creator: dernst
  date_created: 2024-03-25T12:52:04Z
  date_updated: 2024-03-25T12:52:04Z
  file_id: '15188'
  file_name: 2024_JCB_Zens.pdf
  file_size: 11907016
  relation: main_file
  success: 1
file_date_updated: 2024-03-25T12:52:04Z
fulldoi: https://doi.org/10.1083/jcb.202309125
has_accepted_license: '1'
intvolume: '       223'
isi: 1
issue: '6'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
  grant_number: P33367
  name: Structure and isoform diversity of the Arp2/3 complex
- _id: 7bd318a1-9f16-11ee-852c-cc9217763180
  grant_number: E435
  name: In Situ Actin Structures via Hybrid Cryo-electron Microscopy
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular Navigation Along Spatial Gradients
- _id: 059B463C-7A3F-11EA-A408-12923DDC885E
  name: "NÃ\x96-Fonds Preis fÃ¼r die Jungforscherin des Jahres am IST Austria"
- _id: 2615199A-B435-11E9-9278-68D0E5697425
  grant_number: '21317'
  name: Spatiotemporal regulation of chemokine-induced signalling in leukocyte chemotaxis
- _id: 62909c6f-2b32-11ec-9570-e1476aab5308
  grant_number: CZI01
  name: CryoMinflux-guided in-situ visual proteomics and structure determination
publication: Journal of Cell Biology
publication_identifier:
  eissn:
  - 1540-8140
  issn:
  - 0021-9525
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Lift-out cryo-FIBSEM and cryo-ET reveal the ultrastructural landscape of extracellular
  matrix
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 223
year: '2024'
...
---
_id: '17463'
abstract:
- lang: eng
  text: Allosteric modulation of protein function, wherein the binding of an effector
    to a protein triggers conformational changes at distant functional sites, plays
    a central part in the control of metabolism and cell signalling1,2,3. There has
    been considerable interest in designing allosteric systems, both to gain insight
    into the mechanisms underlying such ‘action at a distance’ modulation and to create
    synthetic proteins whose functions can be regulated by effectors4,5,6,7. However,
    emulating the subtle conformational changes distributed across many residues,
    characteristic of natural allosteric proteins, is a significant challenge8,9.
    Here, inspired by the classic Monod–Wyman–Changeux model of cooperativity10, we
    investigate the de novo design of allostery through rigid-body coupling of peptide-switchable
    hinge modules11 to protein interfaces12 that direct the formation of alternative
    oligomeric states. We find that this approach can be used to generate a wide variety
    of allosterically switchable systems, including cyclic rings that incorporate
    or eject subunits in response to peptide binding and dihedral cages that undergo
    effector-induced disassembly. Size-exclusion chromatography, mass photometry13
    and electron microscopy reveal that these designed allosteric protein assemblies
    closely resemble the design models in both the presence and absence of peptide
    effectors and can have ligand-binding cooperativity comparable to classic natural
    systems such as haemoglobin14. Our results indicate that allostery can arise from
    global coupling of the energetics of protein substructures without optimized side-chain–side-chain
    allosteric communication pathways and provide a roadmap for generating allosterically
    triggerable delivery systems, protein nanomachines and cellular feedback control
    circuitry.
acknowledgement: We thank D. D. Sahtoe, R. D. Kiber, Y. Hsia, N. Bethel and A. Favor
  for helpful discussions and K. VanWormer and L. Goldschmidt for technical support.
  We also thank X. Li and M. Lamb for mass spectrometry support. This work was supported
  by the Washington Research Foundation Postdoctoral Fellowship (grant no. GR027504,
  A. Pillai), a National Science Foundation Graduate Research Fellowship (grant no.
  DGE-2140004, A.I.), a Human Frontier Science Program Long Term Fellowship (grant
  no. LT000880/2019, F.P.), the Audacious Project at the Institute for Protein Design
  (A.B., A. Pillai, A. Philomin, A.I. and D.B.), a National Energy Research Scientific
  Computing Centre award (grant no. BER-ERCAP0022018), the Howard Hughes Medical Institute
  (D.B.), the Open Philanthropy Project Improving Protein Design Fund (P.J.Y.L., C.D.
  and D.B.) a gift from Microsoft (D.B.) and a grant from DARPA supporting the Harnessing
  Enzymatic Activity for Lifesaving Remedies programme (grant no. HR001120S0052, contract
  no. HR0011-21-2-0012, D.B.).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Arvind
  full_name: Pillai, Arvind
  last_name: Pillai
- first_name: Abbas
  full_name: Idris, Abbas
  last_name: Idris
- first_name: Annika
  full_name: Philomin, Annika
  last_name: Philomin
- first_name: Connor
  full_name: Weidle, Connor
  last_name: Weidle
- first_name: Rebecca
  full_name: Skotheim, Rebecca
  last_name: Skotheim
- first_name: Philip J.Y.
  full_name: Leung, Philip J.Y.
  last_name: Leung
- first_name: Adam
  full_name: Broerman, Adam
  last_name: Broerman
- first_name: Cullen
  full_name: Demakis, Cullen
  last_name: Demakis
- first_name: Andrew J.
  full_name: Borst, Andrew J.
  last_name: Borst
- first_name: Florian M
  full_name: Praetorius, Florian M
  id: dfec9381-4341-11ee-8fd8-faa02bba7d62
  last_name: Praetorius
  orcid: 0000-0002-0806-8101
- first_name: David
  full_name: Baker, David
  last_name: Baker
citation:
  ama: Pillai A, Idris A, Philomin A, et al. De novo design of allosterically switchable
    protein assemblies. <i>Nature</i>. 2024;632:911–920. doi:<a href="https://doi.org/10.1038/s41586-024-07813-2">10.1038/s41586-024-07813-2</a>
  apa: Pillai, A., Idris, A., Philomin, A., Weidle, C., Skotheim, R., Leung, P. J.
    Y., … Baker, D. (2024). De novo design of allosterically switchable protein assemblies.
    <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-024-07813-2">https://doi.org/10.1038/s41586-024-07813-2</a>
  chicago: Pillai, Arvind, Abbas Idris, Annika Philomin, Connor Weidle, Rebecca Skotheim,
    Philip J.Y. Leung, Adam Broerman, et al. “De Novo Design of Allosterically Switchable
    Protein Assemblies.” <i>Nature</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41586-024-07813-2">https://doi.org/10.1038/s41586-024-07813-2</a>.
  ieee: A. Pillai <i>et al.</i>, “De novo design of allosterically switchable protein
    assemblies,” <i>Nature</i>, vol. 632. Springer Nature, pp. 911–920, 2024.
  ista: Pillai A, Idris A, Philomin A, Weidle C, Skotheim R, Leung PJY, Broerman A,
    Demakis C, Borst AJ, Praetorius FM, Baker D. 2024. De novo design of allosterically
    switchable protein assemblies. Nature. 632, 911–920.
  mla: Pillai, Arvind, et al. “De Novo Design of Allosterically Switchable Protein
    Assemblies.” <i>Nature</i>, vol. 632, Springer Nature, 2024, pp. 911–920, doi:<a
    href="https://doi.org/10.1038/s41586-024-07813-2">10.1038/s41586-024-07813-2</a>.
  short: A. Pillai, A. Idris, A. Philomin, C. Weidle, R. Skotheim, P.J.Y. Leung, A.
    Broerman, C. Demakis, A.J. Borst, F.M. Praetorius, D. Baker, Nature 632 (2024)
    911–920.
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: All data are available either in the main text or as Supplementary
  Information. PDB models and sequences for designs shown in main text figures are
  available in the attached Supplementary Information, along with source data for
  plots in main text figures. Structures determined by cryo-EM were deposited in the
  PDB as 8UP1, 8URE and 8UTM, and maps were deposited in the EMDB under accession
  numbers EMD-42442, EMD-42491 and EMD-42542.
date_created: 2024-08-25T22:01:08Z
date_published: 2024-08-22T00:00:00Z
date_updated: 2026-10-01T11:19:54Z
day: '22'
ddc:
- '570'
department:
- _id: FlPr
doi: 10.1038/s41586-024-07813-2
external_id:
  isi:
  - '001300534300019'
  pmid:
  - '39143214'
file:
- access_level: open_access
  checksum: 39127601621a360ec0edc538627eb211
  content_type: application/pdf
  creator: dernst
  date_created: 2024-09-09T12:01:14Z
  date_updated: 2024-09-09T12:01:14Z
  file_id: '18005'
  file_name: 2024_Nature_Pillai.pdf
  file_size: 16572040
  relation: main_file
  success: 1
file_date_updated: 2024-09-09T12:01:14Z
fulldoi: https://doi.org/10.1038/s41586-024-07813-2
has_accepted_license: '1'
intvolume: '       632'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '911–920 '
pmid: 1
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes (supplementary data)
scopus_import: '1'
status: public
supplementarymaterial: yes
title: De novo design of allosterically switchable protein assemblies
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 632
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18934'
abstract:
- lang: eng
  text: The assembly of biomolecular condensate in eukaryotic cells and the accumulation
    of amyloid deposits in neurons are processes involving the nucleation and growth
    (NAG) of new protein phases. To therapeutically target protein phase separation,
    drug candidates are tested in in vitro assays that monitor the increase in the
    mass or size of the new phase. Limited mechanistic insight is, however, provided
    if empirical or untestable kinetic models are fitted to these progress curves.
    Here we present the web server NAGPKin that quantifies NAG rates using mass-based
    or size-based progress curves as the input data. A report is generated containing
    the fitted NAG parameters and elucidating the phase separation mechanisms at play.
    The NAG parameters can be used to predict particle size distributions of, for
    example, protein droplets formed by liquid-liquid phase separation (LLPS) or amyloid
    fibrils formed by protein aggregation. Because minimal intervention is required
    from the user, NAGPKin is a good platform for standardized reporting of LLPS and
    protein self-assembly data. NAGPKin is useful for drug discovery as well as for
    fundamental studies on protein phase separation. NAGPKin is freely available (no
    login required) at https://nagpkin.i3s.up.pt .
acknowledgement: We thank Professor José Paulo Leal, Department of Computer Science
  − Faculdade de Ciências da Universidade do Porto, for his invaluable help during
  the Implementation of NAGPKin. This work is part of a project that has received
  funding from the European Union’s Horizon 2020 research and innovation programme
  under grant agreement no. 952334 (PhasAGE). This research was funded by the Portuguese
  Foundation for Science and Technology (FCT) in the framework of project PTDC/QUI-COL/2444/2021.
article_number: mr1
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Zsuzsa
  full_name: Sárkány, Zsuzsa
  last_name: Sárkány
- first_name: Francisco
  full_name: Figueiredo, Francisco
  id: 8125cbe2-9661-11ed-a754-afe96018f37d
  last_name: Figueiredo
- first_name: Sandra
  full_name: Macedo-Ribeiro, Sandra
  last_name: Macedo-Ribeiro
- first_name: Pedro M.
  full_name: Martins, Pedro M.
  last_name: Martins
citation:
  ama: 'Sárkány Z, Figueiredo F, Macedo-Ribeiro S, Martins PM. NAGPKin: Nucleation-and-growth
    parameters from the kinetics of protein phase separation. <i>Molecular Biology
    of the Cell</i>. 2024;35(3). doi:<a href="https://doi.org/10.1091/mbc.e23-07-0289">10.1091/mbc.e23-07-0289</a>'
  apa: 'Sárkány, Z., Figueiredo, F., Macedo-Ribeiro, S., &#38; Martins, P. M. (2024).
    NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation.
    <i>Molecular Biology of the Cell</i>. American Society for Cell Biology. <a href="https://doi.org/10.1091/mbc.e23-07-0289">https://doi.org/10.1091/mbc.e23-07-0289</a>'
  chicago: 'Sárkány, Zsuzsa, Francisco Figueiredo, Sandra Macedo-Ribeiro, and Pedro
    M. Martins. “NAGPKin: Nucleation-and-Growth Parameters from the Kinetics of Protein
    Phase Separation.” <i>Molecular Biology of the Cell</i>. American Society for
    Cell Biology, 2024. <a href="https://doi.org/10.1091/mbc.e23-07-0289">https://doi.org/10.1091/mbc.e23-07-0289</a>.'
  ieee: 'Z. Sárkány, F. Figueiredo, S. Macedo-Ribeiro, and P. M. Martins, “NAGPKin:
    Nucleation-and-growth parameters from the kinetics of protein phase separation,”
    <i>Molecular Biology of the Cell</i>, vol. 35, no. 3. American Society for Cell
    Biology, 2024.'
  ista: 'Sárkány Z, Figueiredo F, Macedo-Ribeiro S, Martins PM. 2024. NAGPKin: Nucleation-and-growth
    parameters from the kinetics of protein phase separation. Molecular Biology of
    the Cell. 35(3), mr1.'
  mla: 'Sárkány, Zsuzsa, et al. “NAGPKin: Nucleation-and-Growth Parameters from the
    Kinetics of Protein Phase Separation.” <i>Molecular Biology of the Cell</i>, vol.
    35, no. 3, mr1, American Society for Cell Biology, 2024, doi:<a href="https://doi.org/10.1091/mbc.e23-07-0289">10.1091/mbc.e23-07-0289</a>.'
  short: Z. Sárkány, F. Figueiredo, S. Macedo-Ribeiro, P.M. Martins, Molecular Biology
    of the Cell 35 (2024).
das_tickbox: '0'
date_created: 2025-01-29T07:58:40Z
date_published: 2024-03-01T00:00:00Z
date_updated: 2026-10-01T11:22:53Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1091/mbc.e23-07-0289
external_id:
  pmid:
  - '38117593'
file:
- access_level: open_access
  checksum: d7deb6390f294da69321cfbe352ed611
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-29T08:12:11Z
  date_updated: 2025-01-29T08:12:11Z
  file_id: '18935'
  file_name: 2024_MolecularBioCell_Sarkany.pdf
  file_size: 1699180
  relation: main_file
  success: 1
file_date_updated: 2025-01-29T08:12:11Z
fulldoi: https://doi.org/10.1091/mbc.e23-07-0289
has_accepted_license: '1'
intvolume: '        35'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Molecular Biology of the Cell
publication_identifier:
  eissn:
  - 1939-4586
  issn:
  - 1059-1524
publication_status: published
publisher: American Society for Cell Biology
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: no
title: 'NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase
  separation'
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 35
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18757'
abstract:
- lang: eng
  text: 'Segmentation is a critical data processing step in many applications of cryo-electron
    tomography. Downstream analyses, such as subtomogram averaging, are often based
    on segmentation results, and are thus critically dependent on the availability
    of open-source software for accurate as well as high-throughput tomogram segmentation.
    There is a need for more user-friendly, flexible, and comprehensive segmentation
    software that offers an insightful overview of all steps involved in preparing
    automated segmentations. Here, we present Ais: a dedicated tomogram segmentation
    package that is geared towards both high performance and accessibility, available
    on GitHub. In this report, we demonstrate two common processing steps that can
    be greatly accelerated with Ais: particle picking for subtomogram averaging, and
    generating many-feature segmentations of cellular architecture based on in situ
    tomography data. Featuring comprehensive annotation, segmentation, and rendering
    functionality, as well as an open repository for trained models at aiscryoet.org,
    we hope that Ais will help accelerate research and dissemination of data involving
    cryoET.'
acknowledgement: 'We thank A Koster and M Barcena for helpful discussions and kindly
  sharing the coronaviral replication organelle datasets. We are also grateful to
  van den Hoek et al., 2022 and Wu et al., 2023, for uploading the data that we used
  for Figure 5 onto EMPIAR and EMDB, as well as to the authors of various other datasets
  uploaded to these databases that are not discussed in this manuscript but that were
  useful for testing the software. We also thank the reviewers, whose comments were
  very helpful in improving the manuscript and the software. Finally, we are grateful
  the early Ais users who provided us with feedback on the software and reported issues.
  This research was supported by the following grants to THS: European Research Council
  H202 Grant 759517; European Union’s Horizon Europe Program IMAGINE grant 101094250,
  and the Netherlands Organization for Scientific Research Grant VI.Vidi.193.014.'
article_number: '98552'
article_processing_charge: Yes
article_type: original
author:
- first_name: Mart G.F.
  full_name: Last, Mart G.F.
  last_name: Last
- first_name: Leoni
  full_name: Abendstein, Leoni
  id: 14f1f051-cd9d-11ef-9c94-8b942a882560
  last_name: Abendstein
  orcid: 0000-0001-7634-5353
- first_name: Lenard M.
  full_name: Voortman, Lenard M.
  last_name: Voortman
- first_name: Thomas H.
  full_name: Sharp, Thomas H.
  last_name: Sharp
citation:
  ama: Last MGF, Abendstein L, Voortman LM, Sharp TH. Streamlining segmentation of
    cryo-electron tomography datasets with Ais. <i>eLife</i>. 2024;13. doi:<a href="https://doi.org/10.7554/eLife.98552">10.7554/eLife.98552</a>
  apa: Last, M. G. F., Abendstein, L., Voortman, L. M., &#38; Sharp, T. H. (2024).
    Streamlining segmentation of cryo-electron tomography datasets with Ais. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.98552">https://doi.org/10.7554/eLife.98552</a>
  chicago: Last, Mart G.F., Leoni Abendstein, Lenard M. Voortman, and Thomas H. Sharp.
    “Streamlining Segmentation of Cryo-Electron Tomography Datasets with Ais.” <i>ELife</i>.
    eLife Sciences Publications, 2024. <a href="https://doi.org/10.7554/eLife.98552">https://doi.org/10.7554/eLife.98552</a>.
  ieee: M. G. F. Last, L. Abendstein, L. M. Voortman, and T. H. Sharp, “Streamlining
    segmentation of cryo-electron tomography datasets with Ais,” <i>eLife</i>, vol.
    13. eLife Sciences Publications, 2024.
  ista: Last MGF, Abendstein L, Voortman LM, Sharp TH. 2024. Streamlining segmentation
    of cryo-electron tomography datasets with Ais. eLife. 13, 98552.
  mla: Last, Mart G. F., et al. “Streamlining Segmentation of Cryo-Electron Tomography
    Datasets with Ais.” <i>ELife</i>, vol. 13, 98552, eLife Sciences Publications,
    2024, doi:<a href="https://doi.org/10.7554/eLife.98552">10.7554/eLife.98552</a>.
  short: M.G.F. Last, L. Abendstein, L.M. Voortman, T.H. Sharp, ELife 13 (2024).
das_tickbox: '1'
dataavailabilitystatement: Source code is available via GitHub, (copy archived at
  Last, 2024), software available on the python package index as 'Ais-cryoET'. Trained
  neural networks have been uploaded to aiscryoet.org.
date_created: 2025-01-05T23:01:57Z
date_published: 2024-12-20T00:00:00Z
date_updated: 2026-10-01T11:22:32Z
day: '20'
ddc:
- '570'
department:
- _id: FlPr
doi: 10.7554/eLife.98552
external_id:
  pmid:
  - '39704648'
file:
- access_level: open_access
  checksum: a4f0f906e4d5c1078208b317e78699d1
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-08T08:51:45Z
  date_updated: 2025-01-08T08:51:45Z
  file_id: '18774'
  file_name: 2024_eLife_Last.pdf
  file_size: 7445664
  relation: main_file
  success: 1
file_date_updated: 2025-01-08T08:51:45Z
fulldoi: https://doi.org/10.7554/eLife.98552
has_accepted_license: '1'
intvolume: '        13'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Streamlining segmentation of cryo-electron tomography datasets with Ais
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 13
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '18445'
abstract:
- lang: eng
  text: Acquisition of specialized cellular features is controlled by the ordered
    expression of transcription factors (TFs) along differentiation trajectories.
    Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic
    neurons that leave their Ascl1+/Onecut1/2+ proliferative domain in the vertebrate
    hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq
    and gain-of-function experiments for gene network reconstruction to show that
    ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived
    dopamine and thyrotropin-releasing hormone (TRH)+ glutamate neurons through neuron
    navigator-2 (NAV2). In vivo, siRNA-mediated knockdown of ONECUT3 in neonatal mice
    reduced NAV2 mRNA, as well as neurite complexity in Onecut3-containing neurons,
    while genetic deletion of Onecut3/ceh-48 in C. elegans impaired neurocircuit wiring,
    and sensory discrimination-based behaviors. Thus, ONECUT3, conserved across neuronal
    subtypes and many species, underpins the polarization and morphological plasticity
    of phenotypically distinct neurons that descend from a common pool of Ascl1+ progenitors
    in the hypothalamus.
acknowledgement: "The authors thank Z. Máté, G. Szabó, and F. Erdélyi for the custom
  generation of transgenic mouse lines, C. Fekete for Trh transgenic tissues (all
  from the Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest,
  Hungary), A. Goudmaeker for IVF recovery of a frozen mouse line (SSS animal facility,
  Université catholique de Louvain), and Y. Yanagawa (Department of Genetic and Behavioral
  Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan) for
  providing GAD67gfp/+ mice. We also thank S. Cloer, D. Preininger, and A. Weissenbacher
  (Tiergarten Schönbrunn, Vienna, Austria) for providing naked mole rats, Seba’s fruit
  bats, and Indian flying foxes, as well as F. Aujard (CNRS, UMR 7179 ‘Adaptive mechanisms
  and evolution’, France) for Microcebus tissues. I. Milenkovic and G.G. Kovács (Clinical
  Institute of Neurology, Medical University of Vienna, Vienna, Austria) are acknowledged
  for providing post-mortem human brain samples. We are indebted to S. Rehman (Medical
  University of Vienna), M. Kalusa (University of Leipzig, Leipzig, Germany), and
  W. Reimann (Paul Flechsig Institute for Brain Research, Leipzig, Germany) for their
  technical assistance. C. elegans strains were provided by the National Bioresource
  Project for the nematode, Japan, and the CGC, with the latter being funded by the
  NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported
  by the Austrian Science Fund (FWF, P 34121-B; to E.K.), the Swedish Research Council
  (2023-03058, T.Ha; 2020-01688, T.Hö.), the Swedish Brain Foundation (Hjärnfonden,
  FO2022-0300, to T.Ha.), the Novo Nordisk Foundation (NNF23OC0084476, to T.Ha.),
  the European Research Council (FOODFORLIFE, ERC-2020-AdG-101021016; to T.Ha.), the
  Université Catholique de Louvain (‘Fonds spéciaux de recherche’-FSR, to F.C.), and
  Fonds de la Recherche Scientifique F.R.S.-FNRS (‘Project de recherche (PDR)’ #T.0039.21,
  to F.C.). S.J.E. is supported by the Simons Foundation #543069. I.L. is supported
  by a post-doctoral fellowship from the Human Frontiers Science Program (LT000335/2020-L).
  E.R. holds a PhD grant from the FRIA (F.R.S.-FNRS, Belgium). F.C. is a Research
  Director of the F.R.S.-FNRS (Belgium).\r\nOpen access funding provided by Karolinska
  Institute."
article_number: '8631'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Maja
  full_name: Zupančič, Maja
  last_name: Zupančič
- first_name: Erik
  full_name: Keimpema, Erik
  last_name: Keimpema
- first_name: Evgenii O.
  full_name: Tretiakov, Evgenii O.
  last_name: Tretiakov
- first_name: Stephanie J.
  full_name: Eder, Stephanie J.
  last_name: Eder
- first_name: Itamar
  full_name: Lev, Itamar
  last_name: Lev
- first_name: Lukas
  full_name: Englmaier, Lukas
  last_name: Englmaier
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: Simone A.
  full_name: Fietz, Simone A.
  last_name: Fietz
- first_name: Wolfgang
  full_name: Härtig, Wolfgang
  last_name: Härtig
- first_name: Estelle
  full_name: Renaux, Estelle
  last_name: Renaux
- first_name: Andreas
  full_name: Villunger, Andreas
  last_name: Villunger
- first_name: Tomas
  full_name: Hökfelt, Tomas
  last_name: Hökfelt
- first_name: Manuel
  full_name: Zimmer, Manuel
  last_name: Zimmer
- first_name: Frédéric
  full_name: Clotman, Frédéric
  last_name: Clotman
- first_name: Tibor
  full_name: Harkany, Tibor
  last_name: Harkany
citation:
  ama: Zupančič M, Keimpema E, Tretiakov EO, et al. Concerted transcriptional regulation
    of the morphogenesis of hypothalamic neurons by ONECUT3. <i>Nature Communications</i>.
    2024;15. doi:<a href="https://doi.org/10.1038/s41467-024-52762-z">10.1038/s41467-024-52762-z</a>
  apa: Zupančič, M., Keimpema, E., Tretiakov, E. O., Eder, S. J., Lev, I., Englmaier,
    L., … Harkany, T. (2024). Concerted transcriptional regulation of the morphogenesis
    of hypothalamic neurons by ONECUT3. <i>Nature Communications</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41467-024-52762-z">https://doi.org/10.1038/s41467-024-52762-z</a>
  chicago: Zupančič, Maja, Erik Keimpema, Evgenii O. Tretiakov, Stephanie J. Eder,
    Itamar Lev, Lukas Englmaier, Pradeep Bhandari, et al. “Concerted Transcriptional
    Regulation of the Morphogenesis of Hypothalamic Neurons by ONECUT3.” <i>Nature
    Communications</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41467-024-52762-z">https://doi.org/10.1038/s41467-024-52762-z</a>.
  ieee: M. Zupančič <i>et al.</i>, “Concerted transcriptional regulation of the morphogenesis
    of hypothalamic neurons by ONECUT3,” <i>Nature Communications</i>, vol. 15. Springer
    Nature, 2024.
  ista: Zupančič M, Keimpema E, Tretiakov EO, Eder SJ, Lev I, Englmaier L, Bhandari
    P, Fietz SA, Härtig W, Renaux E, Villunger A, Hökfelt T, Zimmer M, Clotman F,
    Harkany T. 2024. Concerted transcriptional regulation of the morphogenesis of
    hypothalamic neurons by ONECUT3. Nature Communications. 15, 8631.
  mla: Zupančič, Maja, et al. “Concerted Transcriptional Regulation of the Morphogenesis
    of Hypothalamic Neurons by ONECUT3.” <i>Nature Communications</i>, vol. 15, 8631,
    Springer Nature, 2024, doi:<a href="https://doi.org/10.1038/s41467-024-52762-z">10.1038/s41467-024-52762-z</a>.
  short: M. Zupančič, E. Keimpema, E.O. Tretiakov, S.J. Eder, I. Lev, L. Englmaier,
    P. Bhandari, S.A. Fietz, W. Härtig, E. Renaux, A. Villunger, T. Hökfelt, M. Zimmer,
    F. Clotman, T. Harkany, Nature Communications 15 (2024).
das_tickbox: '1'
dataavailabilitystatement: The snRNA-seq data generated in this study have been deposited
  in the NCBI Gene Expression Omnibus database under accession code GSE132730 and
  as ‘Supplementary Data 1 - Neuro2a-onecut3-overexpression’. All other primary data
  were made publically available at https://github.com/Harkany-Lab/Zupancic_2023 and
  deposited to Figshare.com with https://doi.org/10.6084/m9.figshare.22680433. Source
  data are provided with this paper.
date_created: 2024-10-20T22:02:05Z
date_published: 2024-10-05T00:00:00Z
date_updated: 2026-10-01T12:17:25Z
day: '05'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1038/s41467-024-52762-z
external_id:
  isi:
  - '001409493300014'
  pmid:
  - '39366958'
file:
- access_level: open_access
  checksum: 03d6dd1b84efa24e9e9ede748d08764d
  content_type: application/pdf
  creator: dernst
  date_created: 2024-10-21T12:15:38Z
  date_updated: 2024-10-21T12:15:38Z
  file_id: '18460'
  file_name: 2024_NatureComm_Zupancic.pdf
  file_size: 7215329
  relation: main_file
  success: 1
file_date_updated: 2024-10-21T12:15:38Z
fulldoi: https://doi.org/10.1038/s41467-024-52762-z
has_accepted_license: '1'
intvolume: '        15'
isi: 1
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '22961'
    relation: research_data
    status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons
  by ONECUT3
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 15
year: '2024'
...
---
_id: '14213'
abstract:
- lang: eng
  text: We introduce a method to segment the visual field into independently moving
    regions, trained with no ground truth or supervision. It consists of an adversarial
    conditional encoder-decoder architecture based on Slot Attention, modified to
    use the image as context to decode optical flow without attempting to reconstruct
    the image itself. In the resulting multi-modal representation, one modality (flow)
    feeds the encoder to produce separate latent codes (slots), whereas the other
    modality (image) conditions the decoder to generate the first (flow) from the
    slots. This design frees the representation from having to encode complex nuisance
    variability in the image due to, for instance, illumination and reflectance properties
    of the scene. Since customary autoencoding based on minimizing the reconstruction
    error does not preclude the entire flow from being encoded into a single slot,
    we modify the loss to an adversarial criterion based on Contextual Information
    Separation. The resulting min-max optimization fosters the separation of objects
    and their assignment to different attention slots, leading to Divided Attention,
    or DivA. DivA outperforms recent unsupervised multi-object motion segmentation
    methods while tripling run-time speed up to 104FPS and reducing the performance
    gap from supervised methods to 12% or less. DivA can handle different numbers
    of objects and different image sizes at training and test time, is invariant to
    permutation of object labels, and does not require explicit regularization.
article_processing_charge: No
arxiv: 1
author:
- first_name: Dong
  full_name: Lao, Dong
  last_name: Lao
- first_name: Zhengyang
  full_name: Hu, Zhengyang
  last_name: Hu
- first_name: Francesco
  full_name: Locatello, Francesco
  id: 26cfd52f-2483-11ee-8040-88983bcc06d4
  last_name: Locatello
  orcid: 0000-0002-4850-0683
- first_name: Yanchao
  full_name: Yang, Yanchao
  last_name: Yang
- first_name: Stefano
  full_name: Soatto, Stefano
  last_name: Soatto
citation:
  ama: 'Lao D, Hu Z, Locatello F, Yang Y, Soatto S. Divided attention: Unsupervised
    multi-object discovery with contextually separated slots. In: <i>1st Conference
    on Parsimony and Learning</i>. ; 2024.'
  apa: 'Lao, D., Hu, Z., Locatello, F., Yang, Y., &#38; Soatto, S. (2024). Divided
    attention: Unsupervised multi-object discovery with contextually separated slots.
    In <i>1st Conference on Parsimony and Learning</i>. Hong Kong, China.'
  chicago: 'Lao, Dong, Zhengyang Hu, Francesco Locatello, Yanchao Yang, and Stefano
    Soatto. “Divided Attention: Unsupervised Multi-Object Discovery with Contextually
    Separated Slots.” In <i>1st Conference on Parsimony and Learning</i>, 2024.'
  ieee: 'D. Lao, Z. Hu, F. Locatello, Y. Yang, and S. Soatto, “Divided attention:
    Unsupervised multi-object discovery with contextually separated slots,” in <i>1st
    Conference on Parsimony and Learning</i>, Hong Kong, China, 2024.'
  ista: 'Lao D, Hu Z, Locatello F, Yang Y, Soatto S. 2024. Divided attention: Unsupervised
    multi-object discovery with contextually separated slots. 1st Conference on Parsimony
    and Learning. CPAL: Conference on Parsimony and Learning.'
  mla: 'Lao, Dong, et al. “Divided Attention: Unsupervised Multi-Object Discovery
    with Contextually Separated Slots.” <i>1st Conference on Parsimony and Learning</i>,
    2024.'
  short: D. Lao, Z. Hu, F. Locatello, Y. Yang, S. Soatto, in:, 1st Conference on Parsimony
    and Learning, 2024.
conference:
  end_date: 2024-01-03
  location: Hong Kong, China
  name: 'CPAL: Conference on Parsimony and Learning'
  start_date: 2024-01-03
das_tickbox: '0'
date_created: 2023-08-22T14:19:59Z
date_published: 2024-01-03T00:00:00Z
date_updated: 2026-10-01T11:25:45Z
day: '03'
ddc:
- '000'
department:
- _id: FrLo
external_id:
  arxiv:
  - '2304.01430'
file:
- access_level: open_access
  checksum: 8fad894c34f1b3d5a14fb8ffb12f7277
  content_type: application/pdf
  creator: dernst
  date_created: 2024-02-12T08:40:36Z
  date_updated: 2024-02-12T08:40:36Z
  file_id: '14978'
  file_name: 2024_CPAL_Lao.pdf
  file_size: 8038511
  relation: main_file
  success: 1
file_date_updated: 2024-02-12T08:40:36Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
publication: 1st Conference on Parsimony and Learning
publication_status: published
quality_controlled: '1'
researchdata_availability: no
status: public
supplementarymaterial: no
title: 'Divided attention: Unsupervised multi-object discovery with contextually separated
  slots'
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: publisher
OA_type: diamond
_id: '18114'
abstract:
- lang: eng
  text: This paper presents Mechanistic Neural Networks, a neural network design for
    machine learning applications in the sciences. It incorporates a new Mechanistic
    Block in standard architectures to explicitly learn governing differential equations
    as representations, revealing the underlying dynamics of data and enhancing interpretability
    and efficiency in data modeling. Central to our approach is a novel Relaxed Linear
    Programming Solver (NeuRLP) inspired by a technique that reduces solving linear
    ODEs to solving linear programs. This integrates well with neural networks and
    surpasses the limitations of traditional ODE solvers enabling scalable GPU parallel
    processing. Overall, Mechanistic Neural Networks demonstrate their versatility
    for scientific machine learning applications, adeptly managing tasks from equation
    discovery to dynamic systems modeling. We prove their comprehensive capabilities
    in analyzing and interpreting complex scientific data across various applications,
    showing significant performance against specialized state-of-the-art methods.
    Source code is available at https://github.com/alpz/mech-nn.
alternative_title:
- PMLR
article_processing_charge: No
arxiv: 1
author:
- first_name: Adeel A
  full_name: Pervez, Adeel A
  id: fca6d90c-d47f-11ee-bc87-93ff51604981
  last_name: Pervez
- first_name: Francesco
  full_name: Locatello, Francesco
  id: 26cfd52f-2483-11ee-8040-88983bcc06d4
  last_name: Locatello
  orcid: 0000-0002-4850-0683
- first_name: Efstratios
  full_name: Gavves, Efstratios
  last_name: Gavves
citation:
  ama: 'Pervez AA, Locatello F, Gavves E. Mechanistic neural networks for scientific
    machine learning. In: <i>Proceedings of the 41st International Conference on Machine
    Learning</i>. Vol 235. ML Research Press; 2024:40484-40501.'
  apa: 'Pervez, A. A., Locatello, F., &#38; Gavves, E. (2024). Mechanistic neural
    networks for scientific machine learning. In <i>Proceedings of the 41st International
    Conference on Machine Learning</i> (Vol. 235, pp. 40484–40501). Vienna, Austria:
    ML Research Press.'
  chicago: Pervez, Adeel A, Francesco Locatello, and Efstratios Gavves. “Mechanistic
    Neural Networks for Scientific Machine Learning.” In <i>Proceedings of the 41st
    International Conference on Machine Learning</i>, 235:40484–501. ML Research Press,
    2024.
  ieee: A. A. Pervez, F. Locatello, and E. Gavves, “Mechanistic neural networks for
    scientific machine learning,” in <i>Proceedings of the 41st International Conference
    on Machine Learning</i>, Vienna, Austria, 2024, vol. 235, pp. 40484–40501.
  ista: 'Pervez AA, Locatello F, Gavves E. 2024. Mechanistic neural networks for scientific
    machine learning. Proceedings of the 41st International Conference on Machine
    Learning. ICML: International Conference on Machine Learning, PMLR, vol. 235,
    40484–40501.'
  mla: Pervez, Adeel A., et al. “Mechanistic Neural Networks for Scientific Machine
    Learning.” <i>Proceedings of the 41st International Conference on Machine Learning</i>,
    vol. 235, ML Research Press, 2024, pp. 40484–501.
  short: A.A. Pervez, F. Locatello, E. Gavves, in:, Proceedings of the 41st International
    Conference on Machine Learning, ML Research Press, 2024, pp. 40484–40501.
conference:
  end_date: 2024-07-27
  location: Vienna, Austria
  name: 'ICML: International Conference on Machine Learning'
  start_date: 2024-07-21
das_tickbox: '0'
date_created: 2024-09-22T22:01:43Z
date_published: 2024-09-01T00:00:00Z
date_updated: 2026-10-01T11:26:09Z
day: '01'
ddc:
- '000'
department:
- _id: FrLo
external_id:
  arxiv:
  - '2402.13077'
intvolume: '       235'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2402.13077
month: '09'
oa: 1
oa_version: Published Version
page: 40484-40501
publication: Proceedings of the 41st International Conference on Machine Learning
publication_identifier:
  eissn:
  - 2640-3498
publication_status: published
publisher: ML Research Press
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/alpz/mech-nn
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Mechanistic neural networks for scientific machine learning
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 235
year: '2024'
...
---
DOAJ_listed: '1'
_id: '15257'
abstract:
- lang: eng
  text: Root gravitropic bending represents a fundamental aspect of terrestrial plant
    physiology. Gravity is perceived by sedimentation of starch-rich plastids (statoliths)
    to the bottom of the central root cap cells. Following gravity perception, intercellular
    auxin transport is redirected downwards leading to an asymmetric auxin accumulation
    at the lower root side causing inhibition of cell expansion, ultimately resulting
    in downwards bending. How gravity-induced statoliths repositioning is translated
    into asymmetric auxin distribution remains unclear despite PIN auxin efflux carriers
    and the Negative Gravitropic Response of roots (NGR) proteins polarize along statolith
    sedimentation, thus providing a plausible mechanism for auxin flow redirection.
    In this study, using a functional NGR1-GFP construct, we visualized the NGR1 localization
    on the statolith surface and plasma membrane (PM) domains in close proximity to
    the statoliths, correlating with their movements. We determined that NGR1 binding
    to these PM domains is indispensable for NGR1 functionality and relies on cysteine
    acylation and adjacent polybasic regions as well as on lipid and sterol PM composition.
    Detailed timing of the early events following graviperception suggested that both
    NGR1 repolarization and initial auxin asymmetry precede the visible PIN3 polarization.
    This discrepancy motivated us to unveil a rapid, NGR-dependent translocation of
    PIN-activating AGCVIII kinase D6PK towards lower PMs of gravity-perceiving cells,
    thus providing an attractive model for rapid redirection of auxin fluxes following
    gravistimulation.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: 'The research leading to these results has received funding from
  the European Research Council (ERC) under the European Union’s Horizon 2020 research
  and innovation programme grant agreement No 742985 and Austrian Science Fund (FWF):
  I3630-775 B25 to J.F. This research was also supported by the Lab Support Facility
  (LSF) and the Imaging and Optics Facility (IOF) of IST Austria, namely Tereza Bělinová
  for her help with the imaging. JS was supported by FemTECH fellowship.'
article_number: '91523'
article_processing_charge: Yes
article_type: original
author:
- first_name: Ivan
  full_name: Kulich, Ivan
  id: 57a1567c-8314-11eb-9063-c9ddc3451a54
  last_name: Kulich
- first_name: Julia
  full_name: Schmid, Julia
  id: 07cf4637-baaf-11ee-9227-e1de57d1d69b
  last_name: Schmid
- first_name: Anastasiia
  full_name: Teplova, Anastasiia
  id: e3736151-106c-11ec-b916-c2558e2762c6
  last_name: Teplova
- first_name: Linlin
  full_name: Qi, Linlin
  id: 44B04502-A9ED-11E9-B6FC-583AE6697425
  last_name: Qi
  orcid: 0000-0001-5187-8401
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Kulich I, Schmid J, Teplova A, Qi L, Friml J. Rapid translocation of NGR proteins
    driving polarization of PIN-activating D6 protein kinase during root gravitropism.
    <i>eLife</i>. 2024;12. doi:<a href="https://doi.org/10.7554/elife.91523">10.7554/elife.91523</a>
  apa: Kulich, I., Schmid, J., Teplova, A., Qi, L., &#38; Friml, J. (2024). Rapid
    translocation of NGR proteins driving polarization of PIN-activating D6 protein
    kinase during root gravitropism. <i>ELife</i>. eLife Sciences Publications. <a
    href="https://doi.org/10.7554/elife.91523">https://doi.org/10.7554/elife.91523</a>
  chicago: Kulich, Ivan, Julia Schmid, Anastasiia Teplova, Linlin Qi, and Jiří Friml.
    “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6
    Protein Kinase during Root Gravitropism.” <i>ELife</i>. eLife Sciences Publications,
    2024. <a href="https://doi.org/10.7554/elife.91523">https://doi.org/10.7554/elife.91523</a>.
  ieee: I. Kulich, J. Schmid, A. Teplova, L. Qi, and J. Friml, “Rapid translocation
    of NGR proteins driving polarization of PIN-activating D6 protein kinase during
    root gravitropism,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2024.
  ista: Kulich I, Schmid J, Teplova A, Qi L, Friml J. 2024. Rapid translocation of
    NGR proteins driving polarization of PIN-activating D6 protein kinase during root
    gravitropism. eLife. 12, 91523.
  mla: Kulich, Ivan, et al. “Rapid Translocation of NGR Proteins Driving Polarization
    of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>, vol.
    12, 91523, eLife Sciences Publications, 2024, doi:<a href="https://doi.org/10.7554/elife.91523">10.7554/elife.91523</a>.
  short: I. Kulich, J. Schmid, A. Teplova, L. Qi, J. Friml, ELife 12 (2024).
corr_author: '1'
date_created: 2024-04-02T11:35:58Z
date_published: 2024-03-05T00:00:00Z
date_updated: 2026-10-02T07:48:48Z
day: '05'
ddc:
- '580'
department:
- _id: JiFr
doi: 10.7554/elife.91523
ec_funded: 1
external_id:
  pmid:
  - '38441122'
file:
- access_level: open_access
  checksum: a73a84d3bf97a6d09d24308ca6dd0a0c
  content_type: application/pdf
  creator: dernst
  date_created: 2024-04-03T13:18:00Z
  date_updated: 2024-04-03T13:18:00Z
  file_id: '15288'
  file_name: 2024_eLife_Kulich.pdf
  file_size: 11451904
  relation: main_file
  success: 1
file_date_updated: 2024-04-03T13:18:00Z
fulldoi: https://doi.org/10.7554/elife.91523
has_accepted_license: '1'
intvolume: '        12'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 26538374-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03630
  name: Molecular mechanisms of endocytic cargo recognition in plants
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/beneath-the-surface/
  record:
  - id: '22984'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Rapid translocation of NGR proteins driving polarization of PIN-activating
  D6 protein kinase during root gravitropism
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2024'
...
