---
APC_amount: 6828 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18444'
abstract:
- lang: eng
  text: Animals rely on compensatory actions to maintain stability and navigate their
    environment efficiently. These actions depend on global visual motion cues known
    as optic-flow. While the optomotor response has been the traditional focus for
    studying optic-flow compensation in insects, its simplicity has been insufficient
    to determine the role of the intricate optic-flow processing network involved
    in visual course control. Here, we reveal a series of course control behaviours
    in Drosophila and link them to specific neural circuits. We show that bilateral
    electrical coupling of optic-flow-sensitive neurons in the fly’s lobula plate
    are required for a proper course control. This electrical interaction works alongside
    chemical synapses within the HS-H2 network to control the dynamics and direction
    of turning behaviours. Our findings reveal how insects use bilateral motion cues
    for navigation, assigning a new functional significance to the HS-H2 network and
    suggesting a previously unknown role for gap junctions in non-linear operations.
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: LifeSc
acknowledgement: We thank Georg Ammer and Alexander Borst for sharing anti-ShakB serum
  antibodies. We thank Nélia Varela and Eugenia Chiappe for the w1118;+;10XUAS-IVS-eGFPKir2.1/TM6B
  fly line, Augustin Hrvoje for the shakB[2] line, as well as Jesse Isaacman-Beck
  and Thomas R Clandinin for the gift of y1,w*;20XUAS-IVS-PhiC31;+ fly line. We also
  thank Armel Nicolas and Tomas Masson for the proteomic analysis, Ece Sönmez for
  help with fly crosses and dissections for protein analysis, and Lisa Hofer for assistance
  with the reconstruction experiments. We would also like to thank Laura Burnett for
  drawing scientific illustrations used in the figures. We are particularly grateful
  to members of the Siekhaus, the Kondrashov, and the Chiappe group for providing
  material support and technical advice. We are grateful to Daria Siekhaus, Eugenia
  Chiappe, Alexander Borst, Ben deBivort, and all the members of the Joesch laboratory
  for valuable discussions and comments on the manuscript. Stocks from the Bloomington
  Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center
  were used in this study. The Scientific Service Units of ISTA supported the project
  through resources provided by the Imaging and Optics Facility, MIBA Machine Shop,
  and the Lab Support Facility, as well as Vienna Drosophila Research Centre. This
  work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
  as part of the SPP 2205 – 429960716 (M.J.).
article_number: '8830'
article_processing_charge: Yes
article_type: original
author:
- first_name: Victoria
  full_name: Pokusaeva, Victoria
  id: 3184041C-F248-11E8-B48F-1D18A9856A87
  last_name: Pokusaeva
  orcid: 0000-0001-7660-444X
- first_name: Roshan K
  full_name: Satapathy, Roshan K
  id: 46046B7A-F248-11E8-B48F-1D18A9856A87
  last_name: Satapathy
  orcid: 0009-0006-2974-5075
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: Pokusaeva V, Satapathy RK, Symonova O, Jösch MA. Bilateral interactions of
    optic-flow sensitive neurons coordinate course control in flies. <i>Nature Communications</i>.
    2024;15. doi:<a href="https://doi.org/10.1038/s41467-024-53173-w">10.1038/s41467-024-53173-w</a>
  apa: Pokusaeva, V., Satapathy, R. K., Symonova, O., &#38; Jösch, M. A. (2024). Bilateral
    interactions of optic-flow sensitive neurons coordinate course control in flies.
    <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-024-53173-w">https://doi.org/10.1038/s41467-024-53173-w</a>
  chicago: Pokusaeva, Victoria, Roshan K Satapathy, Olga Symonova, and Maximilian
    A Jösch. “Bilateral Interactions of Optic-Flow Sensitive Neurons Coordinate Course
    Control in Flies.” <i>Nature Communications</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41467-024-53173-w">https://doi.org/10.1038/s41467-024-53173-w</a>.
  ieee: V. Pokusaeva, R. K. Satapathy, O. Symonova, and M. A. Jösch, “Bilateral interactions
    of optic-flow sensitive neurons coordinate course control in flies,” <i>Nature
    Communications</i>, vol. 15. Springer Nature, 2024.
  ista: Pokusaeva V, Satapathy RK, Symonova O, Jösch MA. 2024. Bilateral interactions
    of optic-flow sensitive neurons coordinate course control in flies. Nature Communications.
    15, 8830.
  mla: Pokusaeva, Victoria, et al. “Bilateral Interactions of Optic-Flow Sensitive
    Neurons Coordinate Course Control in Flies.” <i>Nature Communications</i>, vol.
    15, 8830, Springer Nature, 2024, doi:<a href="https://doi.org/10.1038/s41467-024-53173-w">10.1038/s41467-024-53173-w</a>.
  short: V. Pokusaeva, R.K. Satapathy, O. Symonova, M.A. Jösch, Nature Communications
    15 (2024).
corr_author: '1'
date_created: 2024-10-20T22:02:05Z
date_published: 2024-10-12T00:00:00Z
date_updated: 2026-06-10T07:58:34Z
day: '12'
ddc:
- '570'
department:
- _id: MaJö
doi: 10.1038/s41467-024-53173-w
external_id:
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  pmid:
  - '39396050'
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intvolume: '        15'
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language:
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license: https://creativecommons.org/licenses/by/4.0/
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B767A34-BA93-11EA-9121-9846C619BF3A
  grant_number: '429960716'
  name: Evolution of Sensorimotor Transformation Across Diptera
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
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status: public
title: Bilateral interactions of optic-flow sensitive neurons coordinate course control
  in flies
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: publisher
OA_type: hybrid
_id: '18553'
abstract:
- lang: eng
  text: Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates
    DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II).
    TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which
    recruits the CRL4CSA ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at
    RPB1-K1268 by CRL4CSA serves as a critical TC-NER checkpoint, governing RNA Pol
    II stability and initiating DNA damage excision by TFIIH recruitment. However,
    the precise regulatory mechanisms of CRL4CSA activity and TFIIH recruitment remain
    elusive. Here, we reveal human serine/threonine-protein kinase 19 (STK19) as a
    TC-NER factor, which is essential for correct DNA damage removal and subsequent
    transcription restart. Cryogenic electron microscopy (cryo-EM) studies demonstrate
    that STK19 is an integral part of the RNA Pol II-TC-NER complex, bridging CSA,
    UVSSA, RNA Pol II, and downstream DNA. STK19 stimulates TC-NER complex stability
    and CRL4CSA activity, resulting in efficient RNA Pol II ubiquitylation and correct
    UVSSA and TFIIH binding. These findings underscore the crucial role of STK19 as
    a core TC-NER component.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank N. Thompson and R. Burgess for the 8WG16 hybridoma cell
  line. This research was further supported by the Scientific Service Units (SSU)
  of IST Austria through resources provided by the Lab Support Facility (LSF) and
  the Preclinical Facility (PCF). This work is part of the Oncode Institute, which
  is partly financed by the Dutch Cancer Society. Research at the Netherlands Cancer
  Institute is supported by institutional grants of the Dutch Cancer Society and the
  Dutch Ministry of Health, Welfare and Sport. This study was supported by a VICI
  (VI.C.182.025) and a TOP Grant (714.017.003) of the Netherlands Organization for
  Scientific Research.
article_processing_charge: No
article_type: original
author:
- first_name: Anisha R.
  full_name: Ramadhin, Anisha R.
  last_name: Ramadhin
- first_name: Shun-Hsiao
  full_name: Lee, Shun-Hsiao
  last_name: Lee
- first_name: Di
  full_name: Zhou, Di
  last_name: Zhou
- first_name: Anita P
  full_name: Testa Salmazo, Anita P
  id: 41F1F098-F248-11E8-B48F-1D18A9856A87
  last_name: Testa Salmazo
- first_name: Camila
  full_name: Gonzalo-Hansen, Camila
  last_name: Gonzalo-Hansen
- first_name: Marjolein
  full_name: van Sluis, Marjolein
  last_name: van Sluis
- first_name: Cindy M.A.
  full_name: Blom, Cindy M.A.
  last_name: Blom
- first_name: Roel C.
  full_name: Janssens, Roel C.
  last_name: Janssens
- first_name: Anja
  full_name: Raams, Anja
  last_name: Raams
- first_name: Dick
  full_name: Dekkers, Dick
  last_name: Dekkers
- first_name: Karel
  full_name: Bezstarosti, Karel
  last_name: Bezstarosti
- first_name: Dea
  full_name: Slade, Dea
  last_name: Slade
- first_name: Wim
  full_name: Vermeulen, Wim
  last_name: Vermeulen
- first_name: Alex
  full_name: Pines, Alex
  last_name: Pines
- first_name: Jeroen A.A.
  full_name: Demmers, Jeroen A.A.
  last_name: Demmers
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
- first_name: Titia K.
  full_name: Sixma, Titia K.
  last_name: Sixma
- first_name: Jurgen A.
  full_name: Marteijn, Jurgen A.
  last_name: Marteijn
citation:
  ama: Ramadhin AR, Lee S-H, Zhou D, et al. STK19 drives transcription-coupled repair
    by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH
    recruitment. <i>Molecular Cell</i>. 2024;84(24):4740-4757.e12. doi:<a href="https://doi.org/10.1016/j.molcel.2024.10.030">10.1016/j.molcel.2024.10.030</a>
  apa: Ramadhin, A. R., Lee, S.-H., Zhou, D., Testa Salmazo, A. P., Gonzalo-Hansen,
    C., van Sluis, M., … Marteijn, J. A. (2024). STK19 drives transcription-coupled
    repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and
    TFIIH recruitment. <i>Molecular Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.molcel.2024.10.030">https://doi.org/10.1016/j.molcel.2024.10.030</a>
  chicago: Ramadhin, Anisha R., Shun-Hsiao Lee, Di Zhou, Anita P Testa Salmazo, Camila
    Gonzalo-Hansen, Marjolein van Sluis, Cindy M.A. Blom, et al. “STK19 Drives Transcription-Coupled
    Repair by Stimulating Repair Complex Stability, RNA Pol II Ubiquitylation, and
    TFIIH Recruitment.” <i>Molecular Cell</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.molcel.2024.10.030">https://doi.org/10.1016/j.molcel.2024.10.030</a>.
  ieee: A. R. Ramadhin <i>et al.</i>, “STK19 drives transcription-coupled repair by
    stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment,”
    <i>Molecular Cell</i>, vol. 84, no. 24. Elsevier, p. 4740–4757.e12, 2024.
  ista: Ramadhin AR, Lee S-H, Zhou D, Testa Salmazo AP, Gonzalo-Hansen C, van Sluis
    M, Blom CMA, Janssens RC, Raams A, Dekkers D, Bezstarosti K, Slade D, Vermeulen
    W, Pines A, Demmers JAA, Bernecky C, Sixma TK, Marteijn JA. 2024. STK19 drives
    transcription-coupled repair by stimulating repair complex stability, RNA Pol
    II ubiquitylation, and TFIIH recruitment. Molecular Cell. 84(24), 4740–4757.e12.
  mla: Ramadhin, Anisha R., et al. “STK19 Drives Transcription-Coupled Repair by Stimulating
    Repair Complex Stability, RNA Pol II Ubiquitylation, and TFIIH Recruitment.” <i>Molecular
    Cell</i>, vol. 84, no. 24, Elsevier, 2024, p. 4740–4757.e12, doi:<a href="https://doi.org/10.1016/j.molcel.2024.10.030">10.1016/j.molcel.2024.10.030</a>.
  short: A.R. Ramadhin, S.-H. Lee, D. Zhou, A.P. Testa Salmazo, C. Gonzalo-Hansen,
    M. van Sluis, C.M.A. Blom, R.C. Janssens, A. Raams, D. Dekkers, K. Bezstarosti,
    D. Slade, W. Vermeulen, A. Pines, J.A.A. Demmers, C. Bernecky, T.K. Sixma, J.A.
    Marteijn, Molecular Cell 84 (2024) 4740–4757.e12.
date_created: 2024-11-15T12:12:54Z
date_published: 2024-12-19T00:00:00Z
date_updated: 2025-09-08T14:42:50Z
day: '19'
ddc:
- '570'
department:
- _id: CaBe
doi: 10.1016/j.molcel.2024.10.030
external_id:
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  - '001395711300001'
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quality_controlled: '1'
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title: STK19 drives transcription-coupled repair by stimulating repair complex stability,
  RNA Pol II ubiquitylation, and TFIIH recruitment
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 84
year: '2024'
...
---
OA_place: publisher
_id: '18579'
abstract:
- lang: eng
  text: 'Electrophysiological, calcium two-photon recordings and behavioral data for
    Vega-Zuniga et al.  Relevant information can be found in the ''README.txt'' files. '
acknowledged_ssus:
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: Bio
- _id: LifeSc
acknowledgement: Freyja Lange, Michael Schunn, and Todor Asenov
article_processing_charge: No
author:
- first_name: Tomas A
  full_name: Vega Zuniga, Tomas A
  id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
  last_name: Vega Zuniga
- first_name: Anton L
  full_name: Sumser, Anton L
  id: 3320A096-F248-11E8-B48F-1D18A9856A87
  last_name: Sumser
  orcid: 0000-0002-4792-1881
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Florian
  full_name: Schmidt, Florian
  id: A2EF226A-AF19-11E9-924C-0525E6697425
  last_name: Schmidt
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA.
    A thalamic hub-and-spoke network enables visual perception during action by coordinating
    visuomotor dynamics. 2024. doi:<a href="https://doi.org/10.15479/AT:ISTA:18579">10.15479/AT:ISTA:18579</a>
  apa: Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt,
    F., &#38; Jösch, M. A. (2024). A thalamic hub-and-spoke network enables visual
    perception during action by coordinating visuomotor dynamics. Institute of Science
    and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:18579">https://doi.org/10.15479/AT:ISTA:18579</a>
  chicago: Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner,
    Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables
    Visual Perception during Action by Coordinating Visuomotor Dynamics.” Institute
    of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/AT:ISTA:18579">https://doi.org/10.15479/AT:ISTA:18579</a>.
  ieee: T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
    and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during
    action by coordinating visuomotor dynamics.” Institute of Science and Technology
    Austria, 2024.
  ista: Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA.
    2024. A thalamic hub-and-spoke network enables visual perception during action
    by coordinating visuomotor dynamics, Institute of Science and Technology Austria,
    <a href="https://doi.org/10.15479/AT:ISTA:18579">10.15479/AT:ISTA:18579</a>.
  mla: Vega Zuniga, Tomas A., et al. <i>A Thalamic Hub-and-Spoke Network Enables Visual
    Perception during Action by Coordinating Visuomotor Dynamics</i>. Institute of
    Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/AT:ISTA:18579">10.15479/AT:ISTA:18579</a>.
  short: T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
    M.A. Jösch, (2024).
corr_author: '1'
date_created: 2024-11-22T13:48:12Z
date_published: 2024-12-09T00:00:00Z
date_updated: 2026-06-18T18:12:08Z
day: '09'
ddc:
- '570'
department:
- _id: MaJö
doi: 10.15479/AT:ISTA:18579
ec_funded: 1
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oa: 1
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project:
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
- _id: 266D407A-B435-11E9-9278-68D0E5697425
  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
    colliculus
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
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  grant_number: '101086580'
  name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses'
publisher: Institute of Science and Technology Austria
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title: A thalamic hub-and-spoke network enables visual perception during action by
  coordinating visuomotor dynamics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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  short: CC BY (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18596'
abstract:
- lang: eng
  text: Hormone perception and signaling pathways have a fundamental regulatory function
    in the physiological processes of plants. Cytokinins, a class of plant hormones,
    regulate cell division and meristem maintenance. The cytokinin signaling pathway
    is well established in the model plant Arabidopsis thaliana. Several negative
    feedback mechanisms, tightly controlling cytokinin signaling output, have been
    described previously. In this study, we identified a new feedback mechanism executed
    through alternative splicing of the cytokinin receptor AHK4/CRE1. A novel splicing
    variant named CRE1int7 results from seventh intron retention, introducing a premature
    termination codon in the transcript. We showed that CRE1int7 is translated in
    planta into a truncated receptor lacking the C-terminal receiver domain essential
    for signal transduction. CRE1int7 can bind cytokinin but cannot activate the downstream
    cascade. We present a novel negative feedback mechanism of the cytokinin signaling
    pathway, facilitated by a decoy receptor that can inactivate canonical cytokinin
    receptors via dimerization and compete with them for ligand binding. Ensuring
    proper plant growth and development requires precise control of the cytokinin
    signaling pathway at several levels. CRE1int7 represents a so-far unknown mechanism
    for fine-tuning the cytokinin signaling pathway in Arabidopsis.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We dedicate this paper to the deceased Petr Galuszka for his inspiration
  and support of our project. We thank Prof. Peter Hedden for constructive criticism
  of the manuscript and English editing. No conflict of interest is declared.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Michaela
  full_name: Králová, Michaela
  last_name: Králová
- first_name: Ivona
  full_name: Kubalová, Ivona
  last_name: Kubalová
- first_name: Jakub
  full_name: Hajný, Jakub
  last_name: Hajný
- first_name: Karolina
  full_name: Kubiasova, Karolina
  id: 946011F4-3E71-11EA-860B-C7A73DDC885E
  last_name: Kubiasova
  orcid: 0000-0001-5630-9419
- first_name: Karolína
  full_name: Vagaská, Karolína
  last_name: Vagaská
- first_name: Zengxiang
  full_name: Ge, Zengxiang
  id: f43371a3-09ff-11eb-8013-bd0c6a2f6de8
  last_name: Ge
  orcid: 0000-0001-9381-3577
- first_name: Michelle C
  full_name: Gallei, Michelle C
  id: 35A03822-F248-11E8-B48F-1D18A9856A87
  last_name: Gallei
  orcid: 0000-0003-1286-7368
- first_name: Hana
  full_name: Semerádová, Hana
  id: 42FE702E-F248-11E8-B48F-1D18A9856A87
  last_name: Semerádová
- first_name: Anna
  full_name: Kuchařová, Anna
  last_name: Kuchařová
- first_name: Martin
  full_name: Hönig, Martin
  last_name: Hönig
- first_name: Aline
  full_name: Monzer, Aline
  id: 2DB5D88C-D7B3-11E9-B8FD-7907E6697425
  last_name: Monzer
- first_name: Martin
  full_name: Kovačik, Martin
  last_name: Kovačik
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
- first_name: Ondřej
  full_name: Novák, Ondřej
  last_name: Novák
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Yoshihisa
  full_name: Ikeda, Yoshihisa
  last_name: Ikeda
- first_name: David
  full_name: Zalabák, David
  last_name: Zalabák
citation:
  ama: Králová M, Kubalová I, Hajný J, et al. A decoy receptor derived from alternative
    splicing fine-tunes cytokinin signaling in Arabidopsis. <i>Molecular Plant</i>.
    2024;17(12):1850-1865. doi:<a href="https://doi.org/10.1016/j.molp.2024.11.001">10.1016/j.molp.2024.11.001</a>
  apa: Králová, M., Kubalová, I., Hajný, J., Kubiasova, K., Vagaská, K., Ge, Z., …
    Zalabák, D. (2024). A decoy receptor derived from alternative splicing fine-tunes
    cytokinin signaling in Arabidopsis. <i>Molecular Plant</i>. Elsevier. <a href="https://doi.org/10.1016/j.molp.2024.11.001">https://doi.org/10.1016/j.molp.2024.11.001</a>
  chicago: Králová, Michaela, Ivona Kubalová, Jakub Hajný, Karolina Kubiasova, Karolína
    Vagaská, Zengxiang Ge, Michelle C Gallei, et al. “A Decoy Receptor Derived from
    Alternative Splicing Fine-Tunes Cytokinin Signaling in Arabidopsis.” <i>Molecular
    Plant</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.molp.2024.11.001">https://doi.org/10.1016/j.molp.2024.11.001</a>.
  ieee: M. Králová <i>et al.</i>, “A decoy receptor derived from alternative splicing
    fine-tunes cytokinin signaling in Arabidopsis,” <i>Molecular Plant</i>, vol. 17,
    no. 12. Elsevier, pp. 1850–1865, 2024.
  ista: Králová M, Kubalová I, Hajný J, Kubiasova K, Vagaská K, Ge Z, Gallei MC, Semerádová
    H, Kuchařová A, Hönig M, Monzer A, Kovačik M, Friml J, Novák O, Benková E, Ikeda
    Y, Zalabák D. 2024. A decoy receptor derived from alternative splicing fine-tunes
    cytokinin signaling in Arabidopsis. Molecular Plant. 17(12), 1850–1865.
  mla: Králová, Michaela, et al. “A Decoy Receptor Derived from Alternative Splicing
    Fine-Tunes Cytokinin Signaling in Arabidopsis.” <i>Molecular Plant</i>, vol. 17,
    no. 12, Elsevier, 2024, pp. 1850–65, doi:<a href="https://doi.org/10.1016/j.molp.2024.11.001">10.1016/j.molp.2024.11.001</a>.
  short: M. Králová, I. Kubalová, J. Hajný, K. Kubiasova, K. Vagaská, Z. Ge, M.C.
    Gallei, H. Semerádová, A. Kuchařová, M. Hönig, A. Monzer, M. Kovačik, J. Friml,
    O. Novák, E. Benková, Y. Ikeda, D. Zalabák, Molecular Plant 17 (2024) 1850–1865.
date_created: 2024-11-28T11:13:35Z
date_published: 2024-12-02T00:00:00Z
date_updated: 2025-09-08T14:46:45Z
day: '02'
ddc:
- '580'
department:
- _id: JiFr
- _id: EvBe
doi: 10.1016/j.molp.2024.11.001
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month: '12'
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oa_version: Published Version
page: 1850-1865
pmid: 1
publication: Molecular Plant
publication_identifier:
  issn:
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publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A decoy receptor derived from alternative splicing fine-tunes cytokinin signaling
  in Arabidopsis
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: 17
year: '2024'
...
---
OA_place: repository
_id: '18677'
abstract:
- lang: eng
  text: The information-processing capability of the brain’s cellular network depends
    on the physical wiring pattern between neurons and their molecular and functional
    characteristics. Mapping neurons and resolving their individual synaptic connections
    can be achieved by volumetric imaging at nanoscale resolution with dense cellular
    labeling. Light microscopy is uniquely positioned to visualize specific molecules
    but dense, synapse-level circuit reconstruction by light microscopy has been out
    of reach due to limitations in resolution, contrast, and volumetric imaging capability.
    Here we developed light-microscopy based connectomics (LICONN). We integrated
    specifically engineered hydrogel embedding and expansion with comprehensive deep-learning
    based segmentation and analysis of connectivity, thus directly incorporating molecular
    information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level
    brain tissue phenotyping in biological experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: E-Lib
- _id: M-Shop
- _id: LifeSc
- _id: Bio
- _id: ScienComp
acknowledgement: "We thank Sven Dorkenwald and Peter Li for critical reading of the\r\nmanuscript.
  We acknowledge expert support by ISTA’s scientific service units: Imaging and\r\nOptics,
  Lab Support, Scientific Computing, Preclinical Facility, Miba Machine Shop, and
  Library.\r\nWe gratefully acknowledge funding by the following sources:\r\nAustrian
  Science Fund (FWF) grant DK W1232 (JGD, MRT)\r\nAustrian Academy of Sciences DOC
  fellowship 26137 (MRT)\r\nEU Horizon 2020 program, Marie Skłodowska-Curie Actions
  Fellowship 665385 (JL)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022
  (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European
  Research\r\nCouncil (ERC) grant 101044865 “SecretAutism.”\r\n"
article_processing_charge: No
author:
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Michał
  full_name: Januszewski, Michał
  last_name: Januszewski
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Viren
  full_name: Jain, Viren
  last_name: Jain
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy based dense
    connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>
  apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas,
    N., Vorlaufer, J., … Danzl, J. G. (n.d.). Light-microscopy based dense connectomic
    reconstruction of mammalian brain tissue. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.03.01.582884">https://doi.org/10.1101/2024.03.01.582884</a>
  chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou,
    Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy
    Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>,
    n.d. <a href="https://doi.org/10.1101/2024.03.01.582884">https://doi.org/10.1101/2024.03.01.582884</a>.
  ieee: M. Tavakoli <i>et al.</i>, “Light-microscopy based dense connectomic reconstruction
    of mammalian brain tissue,” <i>bioRxiv</i>. .
  ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer
    J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl
    JG. Light-microscopy based dense connectomic reconstruction of mammalian brain
    tissue. bioRxiv, <a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>.
  mla: Tavakoli, Mojtaba, et al. “Light-Microscopy Based Dense Connectomic Reconstruction
    of Mammalian Brain Tissue.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>.
  short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas,
    J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino,
    V. Jain, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-18T14:48:24Z
date_published: 2024-07-08T00:00:00Z
date_updated: 2026-04-28T13:33:34Z
day: '08'
department:
- _id: GaNo
- _id: JoDa
doi: 10.1101/2024.03.01.582884
ec_funded: 1
language:
- iso: eng
main_file_link:
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  url: https://doi.org/10.1101/2024.03.01.582884
month: '07'
oa: 1
oa_version: Preprint
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: bioRxiv
publication_status: draft
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status: public
title: Light-microscopy based dense connectomic reconstruction of mammalian brain
  tissue
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  short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_embargo: '20'
OA_place: publisher
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acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
citation:
  ama: 'Tavakoli M. Developing molecular and structural tools for studying brain architecture
    with super resolution expansion microscopy. LICONN: Molecularly-informed connectomics
    reconstruction with light microscopy. 2024. doi:<a href="https://doi.org/10.15479/at:ista:18681">10.15479/at:ista:18681</a>'
  apa: 'Tavakoli, M. (2024). <i>Developing molecular and structural tools for studying
    brain architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
    connectomics reconstruction with light microscopy</i>. Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/at:ista:18681">https://doi.org/10.15479/at:ista:18681</a>'
  chicago: 'Tavakoli, Mojtaba. “Developing Molecular and Structural Tools for Studying
    Brain Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
    Connectomics Reconstruction with Light Microscopy.” Institute of Science and Technology
    Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18681">https://doi.org/10.15479/at:ista:18681</a>.'
  ieee: 'M. Tavakoli, “Developing molecular and structural tools for studying brain
    architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
    connectomics reconstruction with light microscopy,” Institute of Science and Technology
    Austria, 2024.'
  ista: 'Tavakoli M. 2024. Developing molecular and structural tools for studying
    brain architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
    connectomics reconstruction with light microscopy. Institute of Science and Technology
    Austria.'
  mla: 'Tavakoli, Mojtaba. <i>Developing Molecular and Structural Tools for Studying
    Brain Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
    Connectomics Reconstruction with Light Microscopy</i>. Institute of Science and
    Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18681">10.15479/at:ista:18681</a>.'
  short: 'M. Tavakoli, Developing Molecular and Structural Tools for Studying Brain
    Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
    Connectomics Reconstruction with Light Microscopy, Institute of Science and Technology
    Austria, 2024.'
corr_author: '1'
date_created: 2024-12-19T02:30:39Z
date_published: 2024-12-20T00:00:00Z
date_updated: 2026-04-07T12:56:37Z
day: '20'
ddc:
- '600'
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoDa
doi: 10.15479/at:ista:18681
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language:
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month: '12'
oa_version: Published Version
page: '230'
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication_identifier:
  isbn:
  - 978-3-99078-048-0
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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  - id: '11160'
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  - id: '18688'
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  - id: '18677'
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  - id: '18689'
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status: public
supervisor:
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
title: 'Developing molecular and structural tools for studying brain architecture
  with super resolution expansion microscopy. LICONN: Molecularly-informed connectomics
  reconstruction with light microscopy'
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: repository
_id: '18688'
abstract:
- lang: eng
  text: The human brain has remarkable computational power. It generates sophisticated
    behavioral sequences, stores engrams over an individual’s lifetime, and produces
    higher cognitive functions up to the level of consciousness. However, so little
    of our neuroscience knowledge covers the human brain, and it remains unknown whether
    this organ is truly unique, or is a scaled version of the extensively studied
    rodent brain. To address this fundamental question, we determined the cellular,
    synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using
    multicellular patch clamp-recording. This circuit is the largest autoassociative
    network in the brain, and plays a key role in memory and higher-order computations
    such as pattern separation and pattern completion. We demonstrate that human hippocampal
    CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks.
    Connectivity sparsifies from rodents to humans, providing a circuit architecture
    that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses
    showed both distinct species-specific and circuit-dependent properties, with high
    reliability, unique amplitude precision, and long integration times. We also identify
    differential scaling rules between hippocampal pathways from rodents to humans,
    with a moderate increase in the convergence of CA3 inputs per cell, but a marked
    increase in human mossy fiber innervation. Anatomically guided full-scale modeling
    suggests that the human brain’s sparse connectivity, expanded neuronal number,
    and reliable synaptic signaling combine to enhance the associative memory storage
    capacity of CA3. Together, our results reveal unique rules of connectivity and
    synaptic signaling in the human hippocampus, demonstrating the absolute necessity
    of human brain research and beginning to unravel the remarkable performance of
    our autoassociative memory circuits.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: PreCl
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
  Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
  Asenov for development of the transportation box for human brain tissue, Tim Vogels
  for guidance on simulations, Marcus Huber for mathematical advice, and Eleftheria
  Kralli-Beller for manuscript editing. This research was supported by the Scientific
  Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from
  Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life
  Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge
  the excellent support of the Medical University of Vienna Department of Neurosurgery
  staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry,
  and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology.
  The project received funding from the European Research Council (ERC) under the
  European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie
  Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
  (FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian
  Academy of Sciences (DOC fellowship 26137 to M.R.T.).
article_processing_charge: No
author:
- first_name: Jake F.
  full_name: Watson, Jake F.
  last_name: Watson
- first_name: Victor
  full_name: Vargas-Barroso, Victor
  last_name: Vargas-Barroso
- first_name: Rebecca J.
  full_name: Morse-Mora, Rebecca J.
  last_name: Morse-Mora
- first_name: Andrea
  full_name: Navas-Olive, Andrea
  last_name: Navas-Olive
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Matthias
  full_name: Tomschik, Matthias
  last_name: Tomschik
- first_name: Karl
  full_name: Rössler, Karl
  last_name: Rössler
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses
    specific functional connectivity rules for efficient associative memory. <i>bioRxiv</i>.
    doi:<a href="https://doi.org/10.1101/2024.05.02.592169">10.1101/2024.05.02.592169</a>
  apa: Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli,
    M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional
    connectivity rules for efficient associative memory. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.05.02.592169">https://doi.org/10.1101/2024.05.02.592169</a>
  chicago: Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive,
    Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
    Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
    Efficient Associative Memory.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2024.05.02.592169">https://doi.org/10.1101/2024.05.02.592169</a>.
  ieee: J. F. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional
    connectivity rules for efficient associative memory,” <i>bioRxiv</i>. .
  ista: Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl
    JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional
    connectivity rules for efficient associative memory. bioRxiv, <a href="https://doi.org/10.1101/2024.05.02.592169">10.1101/2024.05.02.592169</a>.
  mla: Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
    Rules for Efficient Associative Memory.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.05.02.592169">10.1101/2024.05.02.592169</a>.
  short: J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli,
    J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T11:35:08Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-14T08:34:32Z
day: '02'
department:
- _id: JoDa
- _id: PeJo
doi: 10.1101/2024.05.02.592169
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.05.02.592169
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '18681'
    relation: dissertation_contains
    status: public
  - id: '18879'
    relation: later_version
    status: public
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
  associative memory
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: repository
_id: '18689'
abstract:
- lang: eng
  text: Multiplexed fluorescence microscopy imaging is widely used in biomedical applications.
    However, simultaneous imaging of multiple fluorophores can result in spectral
    leaks and overlapping, which greatly degrades image quality and subsequent analysis.
    Existing popular spectral unmixing methods are mainly based on computational intensive
    linear models and the performance is heavily dependent on the reference spectra,
    which may greatly preclude its further applications. In this paper, we propose
    a deep learning-based blindly spectral unmixing method, termed AutoUnmix, to imitate
    the physical spectral mixing process. A tranfer learning framework is further
    devised to allow our AutoUnmix adapting to a variety of imaging systems without
    retraining the network. Our proposed method has demonstrated real-time unmixing
    capabilities, surpassing existing methods by up to 100-fold in terms of unmixing
    speed. We further validate the reconstruction performance on both synthetic datasets
    and biological samples. The unmixing results of AutoUnmix achieve a highest SSIM
    of 0.99 in both three- and four-color imaging, with nearly up to 20% higher than
    other popular unmixing methods. Due to the desirable property of data independency
    and superior blind unmixing performance, we believe AutoUnmix is a powerful tool
    to study the interaction process of different organelles labeled by multiple fluorophores.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "We gratefully acknowledge support by the Scientific Service Units
  at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical
  workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\n\r\nThis
  project has received funding from the Austrian Science Fund (FWF): I 3630-B25 (J.G.D)
  and the European Research Council (ERC) under the European Union’s Horizon 2020
  research and innovation programme (grant agreement No 742985, J.F.). It has also
  received funding from the European Union’s Horizon 2020 research and innovation
  programme under the Marie Skłodowska-Curie Grant Agreement No. 665385. S.T. has
  received funding as an ISTplus Fellow from the European Union’s Horizon 2020 Research
  and Innovation Programme under Marie Skłodowska-Curie grant agreement no. 754411
  and from an EMBO Long-Term Fellowship (grant number ALTF 679-2018). It has further
  received funding from the Austrian Science Fund (FWF) grant DK W1232 (M.T, N.A-D.,
  J.G.D). W.J. received funding via a Human Frontier Science Program postdoctoral
  fellowship LT000557/2018.\r\n\r\nThe funders had no role in study design, data collection
  and analysis, decision to publish or preparation of the manuscript."
article_processing_charge: No
author:
- first_name: Michelle C
  full_name: Gallei, Michelle C
  id: 35A03822-F248-11E8-B48F-1D18A9856A87
  last_name: Gallei
  orcid: 0000-0003-1286-7368
- first_name: Sven M
  full_name: Truckenbrodt, Sven M
  id: 45812BD4-F248-11E8-B48F-1D18A9856A87
  last_name: Truckenbrodt
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Syamala
  full_name: Inumella, Syamala
  id: F8660870-D756-11E9-98C5-34DFE5697425
  last_name: Inumella
  orcid: 0009-0002-5890-120X
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Marek
  full_name: Randuch, Marek
  id: 6ac4636d-15b2-11ec-abd3-fb8df79972ae
  last_name: Randuch
- first_name: Alexander J
  full_name: Johnson, Alexander J
  id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
  last_name: Johnson
  orcid: 0000-0002-2739-8843
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion
    microscopy in plant roots. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>
  apa: Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou,
    V., Sommer, C. M., … Danzl, J. G. (n.d.). Super-resolution expansion microscopy
    in plant roots. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.02.21.581330">https://doi.org/10.1101/2024.02.21.581330</a>
  chicago: Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella,
    Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution
    Expansion Microscopy in Plant Roots.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2024.02.21.581330">https://doi.org/10.1101/2024.02.21.581330</a>.
  ieee: M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant
    roots,” <i>bioRxiv</i>. .
  ista: Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM,
    Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková
    E, Friml J, Danzl JG. Super-resolution expansion microscopy in plant roots. bioRxiv,
    <a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>.
  mla: Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant
    Roots.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>.
  short: M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou,
    C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch,
    A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T12:28:00Z
date_published: 2024-02-21T00:00:00Z
date_updated: 2026-04-07T12:56:36Z
day: '21'
department:
- _id: EvBe
- _id: JoDa
- _id: JiFr
doi: 10.1101/2024.02.21.581330
ec_funded: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.02.21.581330
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 269B5B22-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 679-2018
  name: UltraX - achieving sub-nanometer resolution in light microscopy using iterative
    X10 microscopy in combination with nanobodies and STED
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '19003'
    relation: later_version
    status: public
  - id: '18681'
    relation: dissertation_contains
    status: public
status: public
title: Super-resolution expansion microscopy in plant roots
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
_id: '18766'
abstract:
- lang: eng
  text: Poxviruses are large pleomorphic double-stranded DNA viruses that include
    well known members such as variola virus, the causative agent of smallpox, Mpox
    virus, as well as Vaccinia virus (VACV), which serves as a vaccination strain
    for formerly mentioned viruses. VACV is a valuable model for studying large pleomorphic
    DNA viruses in general and poxviruses specifically, as many features, such as
    core morphology and structural proteins, are well conserved within this family.
    Despite decades of research, our understanding of the structural components and
    proteins that comprise the poxvirus core in mature virions remains limited. Although
    major core proteins were identified via indirect experimental evidence, the core's
    complexity, with its large size, structure and number of involved proteins, has
    hindered efforts to achieve high-resolution insights and to define the roles of
    the individual proteins. The specific protein composition of the core's individual
    layers, including the palisade layer and the inner core wall, has remained unclear.
    In this study, we have merged multiple approaches, including single particle cryo
    electron microscopy of purified virus cores, cryo-electron tomography and subtomogram
    averaging of mature virions and molecular modeling to elucidate the structural
    determinants of the VACV core. Due to the lack of experimentally derived structures,
    either in situ or reconstituted in vitro, we used Alphafold to predict models
    of the putative major core protein candidates, A10, 23k, A3, A4, and L4. Our results
    show that the VACV core is composed of several layers with varying local symmetries,
    forming more intricate interactions than observed previously. This allowed us
    to identify several molecular building blocks forming the viral core lattice.
    In particular, we identified trimers of protein A10 as a major core structure
    that forms the palisade layer of the viral core. Additionally, we revealed that
    six petals of a flower shaped core pore within the core wall are composed of A10
    trimers. Furthermore, we obtained a cryo-EM density for the inner core wall that
    could potentially accommodate an A3 dimer. Integrating descriptions of protein
    interactions from previous studies enabled us to provide a detailed structural
    model of the poxvirus core wall, and our findings indicate that the interactions
    within A10 trimers are likely consistent across orthopox- and parapoxviruses.
    This combined application of cryo-SPA and cryo-ET can help overcome obstacles
    in studying complex virus structures in the future, including their key assembly
    proteins, interactions, and the formation into a core lattice. Our work provides
    important fundamental new insights into poxvirus core architecture, also considering
    the recent re-emergence of poxviruses.
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: ScienComp
acknowledgement: "This work was funded by the Austrian Science Fund (FWF) grant P31445
  and ISTA. I\r\nwould like to express my gratitude to the Scientific Service Units,
  particularly the Lab\r\nSupport Facility, the Scientific Computing Facility and
  the Electron Microscopy Facility\r\nfor their tremendous support. I want to especially
  thank Alois for assisting me with the\r\ninstallation of countless new software
  and for troubleshooting cluster issues. A special\r\nthanks goes to Valentin for
  his outstanding support in cryo-EM data acquisition and\r\nhis ongoing help in improving
  the process to ensure that I obtained the best possible\r\ndata from my sample."
alternative_title:
- ISTA thesis
article_processing_charge: No
author:
- first_name: Julia
  full_name: Datler, Julia
  id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
  last_name: Datler
  orcid: 0000-0002-3616-8580
citation:
  ama: Datler J. Elucidating the structural determinants of the poxvirus core using
    multi-modal cryo-EM. 2024. doi:<a href="https://doi.org/10.15479/at:ista:18766">10.15479/at:ista:18766</a>
  apa: Datler, J. (2024). <i>Elucidating the structural determinants of the poxvirus
    core using multi-modal cryo-EM</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/at:ista:18766">https://doi.org/10.15479/at:ista:18766</a>
  chicago: Datler, Julia. “Elucidating the Structural Determinants of the Poxvirus
    Core Using Multi-Modal Cryo-EM.” Institute of Science and Technology Austria,
    2024. <a href="https://doi.org/10.15479/at:ista:18766">https://doi.org/10.15479/at:ista:18766</a>.
  ieee: J. Datler, “Elucidating the structural determinants of the poxvirus core using
    multi-modal cryo-EM,” Institute of Science and Technology Austria, 2024.
  ista: Datler J. 2024. Elucidating the structural determinants of the poxvirus core
    using multi-modal cryo-EM. Institute of Science and Technology Austria.
  mla: Datler, Julia. <i>Elucidating the Structural Determinants of the Poxvirus Core
    Using Multi-Modal Cryo-EM</i>. Institute of Science and Technology Austria, 2024,
    doi:<a href="https://doi.org/10.15479/at:ista:18766">10.15479/at:ista:18766</a>.
  short: J. Datler, Elucidating the Structural Determinants of the Poxvirus Core Using
    Multi-Modal Cryo-EM, Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2025-01-07T10:23:12Z
date_published: 2024-12-30T00:00:00Z
date_updated: 2026-04-07T12:59:44Z
day: '30'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: FlSc
doi: 10.15479/at:ista:18766
file:
- access_level: closed
  checksum: 3e51cab327c754045c3d29c1a50cc9a9
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: jstanger
  date_created: 2025-01-07T12:15:11Z
  date_updated: 2025-01-07T12:15:11Z
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  file_name: PhD_thesis_Julia_Datler.docx
  file_size: 38814932
  relation: source_file
- access_level: open_access
  checksum: 22fabe5b97950bf852212f6edb555173
  content_type: application/pdf
  creator: jstanger
  date_created: 2025-01-07T12:15:14Z
  date_updated: 2025-01-07T12:15:14Z
  file_id: '18770'
  file_name: PhD_thesis_Julia_Datler.pdf
  file_size: 12044865
  relation: main_file
  success: 1
file_date_updated: 2025-01-07T12:15:14Z
has_accepted_license: '1'
keyword:
- cryo-EM
- cryo-ET
- cryo-SPA
- Structural Virology
- Poxvirus
- Vaccinia Virus
- Structural Biology
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '106'
project:
- _id: 26736D6A-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31445
  name: Structural conservation and diversity in retroviral capsid
publication_identifier:
  isbn:
  - 978-3-99078-049-7
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '12334'
    relation: part_of_dissertation
    status: public
  - id: '14979'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
title: Elucidating the structural determinants of the poxvirus core using multi-modal
  cryo-EM
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
_id: '17373'
abstract:
- lang: eng
  text: Scanning Kelvin probe microscopy (SKPM) is a powerful technique for investigating
    the electrostatic properties of material surfaces, enabling the imaging of variations
    in work function, topology, surface charge density, or combinations thereof. Regardless
    of the underlying signal source, SKPM results in a voltage image, which is spatially
    distorted due to the finite size of the probe, long-range electrostatic interactions,
    mechanical and electrical noise, and the finite response time of the electronics.
    In order to recover the underlying signal, it is necessary to deconvolve the measurement
    with an appropriate point spread function (PSF) that accounts the aforementioned
    distortions, but determining this PSF is difficult. Here, we describe how such
    PSFs can be determined experimentally and show how they can be used to recover
    the underlying information of interest. We first consider the physical principles
    that enable SKPM and discuss how these affect the system PSF. We then show how
    one can experimentally measure PSFs by looking at well-defined features, and that
    these compare well to simulated PSFs, provided scans are performed extremely slowly
    and carefully. Next, we work at realistic scan speeds and show that the idealized
    PSFs fail to capture temporal distortions in the scan direction. While simulating
    PSFs for these situations would be quite challenging, we show that measuring PSFs
    with similar scan conditions works well. Our approach clarifies the basic principles
    and inherent challenges to SKPM measurements and gives practical methods to improve
    results.
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
- _id: LifeSc
- _id: ScienComp
acknowledgement: This project has received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant
  Agreement No. 949120). This research was supported by the Scientific Service Units
  of the Institute of Science and Technology Austria (ISTA) through resources provided
  by the Miba Machine Shop, Nanofabrication Facility, Scientific Computing Facility,
  and Lab Support Facility. The authors wish to thank Dmytro Rak and Juan Carlos Sobarzo
  for letting us use their equipment. The authors wish to thank the contributions
  of the whole Waitukaitis Group for useful discussions and feedback.
article_number: '045305'
article_processing_charge: No
article_type: original
author:
- first_name: Isaac C
  full_name: Lenton, Isaac C
  id: a550210f-223c-11ec-8182-e2d45e817efb
  last_name: Lenton
  orcid: 0000-0002-5010-6984
- first_name: Felix
  full_name: Pertl, Felix
  id: 6313aec0-15b2-11ec-abd3-ed67d16139af
  last_name: Pertl
  orcid: 0000-0003-0463-5794
- first_name: Lubuna B
  full_name: Shafeek, Lubuna B
  id: 3CD37A82-F248-11E8-B48F-1D18A9856A87
  last_name: Shafeek
  orcid: 0000-0001-7180-6050
- first_name: Scott R
  full_name: Waitukaitis, Scott R
  id: 3A1FFC16-F248-11E8-B48F-1D18A9856A87
  last_name: Waitukaitis
  orcid: 0000-0002-2299-3176
citation:
  ama: 'Lenton IC, Pertl F, Shafeek LB, Waitukaitis SR. Beyond the blur: Using experimentally
    determined point spread functions to improve scanning Kelvin probe imaging. <i>Journal
    of Applied Physics</i>. 2024;136(4). doi:<a href="https://doi.org/10.1063/5.0215151">10.1063/5.0215151</a>'
  apa: 'Lenton, I. C., Pertl, F., Shafeek, L. B., &#38; Waitukaitis, S. R. (2024).
    Beyond the blur: Using experimentally determined point spread functions to improve
    scanning Kelvin probe imaging. <i>Journal of Applied Physics</i>. AIP Publishing.
    <a href="https://doi.org/10.1063/5.0215151">https://doi.org/10.1063/5.0215151</a>'
  chicago: 'Lenton, Isaac C, Felix Pertl, Lubuna B Shafeek, and Scott R Waitukaitis.
    “Beyond the Blur: Using Experimentally Determined Point Spread Functions to Improve
    Scanning Kelvin Probe Imaging.” <i>Journal of Applied Physics</i>. AIP Publishing,
    2024. <a href="https://doi.org/10.1063/5.0215151">https://doi.org/10.1063/5.0215151</a>.'
  ieee: 'I. C. Lenton, F. Pertl, L. B. Shafeek, and S. R. Waitukaitis, “Beyond the
    blur: Using experimentally determined point spread functions to improve scanning
    Kelvin probe imaging,” <i>Journal of Applied Physics</i>, vol. 136, no. 4. AIP
    Publishing, 2024.'
  ista: 'Lenton IC, Pertl F, Shafeek LB, Waitukaitis SR. 2024. Beyond the blur: Using
    experimentally determined point spread functions to improve scanning Kelvin probe
    imaging. Journal of Applied Physics. 136(4), 045305.'
  mla: 'Lenton, Isaac C., et al. “Beyond the Blur: Using Experimentally Determined
    Point Spread Functions to Improve Scanning Kelvin Probe Imaging.” <i>Journal of
    Applied Physics</i>, vol. 136, no. 4, 045305, AIP Publishing, 2024, doi:<a href="https://doi.org/10.1063/5.0215151">10.1063/5.0215151</a>.'
  short: I.C. Lenton, F. Pertl, L.B. Shafeek, S.R. Waitukaitis, Journal of Applied
    Physics 136 (2024).
corr_author: '1'
date_created: 2024-08-04T22:01:21Z
date_published: 2024-07-28T00:00:00Z
date_updated: 2025-09-08T08:47:42Z
day: '28'
ddc:
- '530'
department:
- _id: ScWa
- _id: NanoFab
doi: 10.1063/5.0215151
ec_funded: 1
external_id:
  isi:
  - '001281681100003'
file:
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  checksum: 6141d05cd68d540a7446dce9490975db
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  date_created: 2024-08-05T08:19:58Z
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intvolume: '       136'
isi: 1
issue: '4'
language:
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month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 0aa60e99-070f-11eb-9043-a6de6bdc3afa
  call_identifier: H2020
  grant_number: '949120'
  name: 'Tribocharge: a multi-scale approach to an enduring problem in physics'
publication: Journal of Applied Physics
publication_identifier:
  eissn:
  - 1089-7550
  issn:
  - 0021-8979
publication_status: published
publisher: AIP Publishing
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Beyond the blur: Using experimentally determined point spread functions to
  improve scanning Kelvin probe imaging'
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: 136
year: '2024'
...
---
OA_place: publisher
_id: '17850'
abstract:
- lang: eng
  text: "Understanding the relationship between a given phenotype and its underlying
    genotype or genotypes is one of the most pressing challenges of biology, as it
    lies at the heart of not only basic understanding of evolutionary theory, but
    also of practical applications in medicine and bioengineering. Understanding this
    relationship is complicated by the ubiquitous phenomenon of epistasis, wherein
    mutation effects are dependent on their genetic context. Fitness landscapes —
    representations of phenotype as a function of genotype — are being increasingly
    used as a tool to study the effects and interactions of thousands of mutations,
    but are experimentally limited to exploring a small fraction of a protein’s theoretical
    sequence space. Furthermore, not all regions of said sequence space are necessarily
    equally informative. Thus, gene selection for landscape surveys should be carefully
    considered in order to maximize the usable output of necessarily limited data.\r\n\r\nIn
    this work, we analyzed the fitness landscapes of orthologous green fluorescent
    proteins from four different species, by systematically measuring the phenotype,
    fluorescence, of tens of thousands of mutant genotypes from each protein. These
    landscapes were highly heterogeneous, with some genes being mutationally robust
    and displaying epistasis only rarely, and others being highly epistatic and mutationally
    fragile. We used this data to train machine learning models to predict fluorescence
    from genotype. Although the training data contained almost exclusively genotypes
    with less than 3% sequence divergence from the original wild-type sequences, we
    were able to create novel, functional genotypes with up to 20% sequence divergence.
    Counterintuitively however, genes with high mutational robustness and rare epistasis
    were more difficult to introduce large numbers of mutations into, not less. This
    represents the first study of large-scale fitness landscapes of a protein family,
    and provides insights into how to approach future landscape surveys and their
    applications in novel protein design."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
citation:
  ama: Gonzalez Somermeyer L. Fitness landscapes of orthologous green fluorescent
    proteins. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17850">10.15479/at:ista:17850</a>
  apa: Gonzalez Somermeyer, L. (2024). <i>Fitness landscapes of orthologous green
    fluorescent proteins</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:17850">https://doi.org/10.15479/at:ista:17850</a>
  chicago: Gonzalez Somermeyer, Louisa. “Fitness Landscapes of Orthologous Green Fluorescent
    Proteins.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17850">https://doi.org/10.15479/at:ista:17850</a>.
  ieee: L. Gonzalez Somermeyer, “Fitness landscapes of orthologous green fluorescent
    proteins,” Institute of Science and Technology Austria, 2024.
  ista: Gonzalez Somermeyer L. 2024. Fitness landscapes of orthologous green fluorescent
    proteins. Institute of Science and Technology Austria.
  mla: Gonzalez Somermeyer, Louisa. <i>Fitness Landscapes of Orthologous Green Fluorescent
    Proteins</i>. Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:17850">10.15479/at:ista:17850</a>.
  short: L. Gonzalez Somermeyer, Fitness Landscapes of Orthologous Green Fluorescent
    Proteins, Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-09-06T12:57:44Z
date_published: 2024-09-06T00:00:00Z
date_updated: 2026-04-07T13:25:01Z
day: '06'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: FyKo
doi: 10.15479/at:ista:17850
ec_funded: 1
file:
- access_level: open_access
  checksum: d3303724e8d3c91321d71bbad4062048
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  creator: lgonzale
  date_created: 2024-09-27T10:32:33Z
  date_updated: 2024-09-27T10:32:33Z
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  date_created: 2024-09-27T10:34:34Z
  date_updated: 2024-09-27T10:34:34Z
  file_id: '18152'
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  relation: source_file
file_date_updated: 2024-09-27T10:34:34Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '89'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 26580278-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '771209'
  name: Characterizing the fitness landscape on population and global scales
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  link:
  - relation: software
    url: https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks
  record:
  - id: '11448'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
title: Fitness landscapes of orthologous green fluorescent proteins
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '17052'
abstract:
- lang: eng
  text: Production of thermoelectric materials from solution-processed particles involves
    the synthesis of particles, their purification and densification into pelletized
    material. Chemical changes that occur during each one of these steps render them
    performance determining. Particularly the purification steps, bypassed in conventional
    solid-state synthesis, are the cause for large discrepancies among similar solution-processed
    materials. In present work, the investigation focuses on a water-based surfactant
    free solution synthesis of SnSe, a highly relevant thermoelectric material. We
    show and rationalize that the number of leaching steps, purification solvent,
    annealing, and annealing atmosphere have significant influence on the Sn : Se
    ratio and impurity content in the powder. Such compositional changes that are
    undetectable by conventional characterization techniques lead to distinct consolidated
    materials with different types and concentration of defects. Additionally, the
    profound effect on their transport properties is demonstrated. We emphasize that
    understanding the chemistry and identifying key chemical species and their role
    throughout the process is paramount for optimizing material performance. Furthermore,
    we aim to demonstrate the necessity of comprehensive reporting of these steps
    as a standard practice to ensure material reproducibility.
acknowledged_ssus:
- _id: EM-Fac
- _id: NMR
- _id: LifeSc
acknowledgement: ISTA and the Werner Siemens Foundation financially supported this
  work. The Scientific Service Units (SSU) of ISTA supported this research through
  resources provided by the Electron Microscopy Facility (EMF), NMR Facility and the
  Lab Support Facility (LSF). Dr. Krishnendu Maji at ISTA aided in this work through
  XRD analysis of the crystal phase of SnSe. Y.L. acknowledges funding from the European
  Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie
  grant agreement No. 754411, the National Natural Science Foundation of China (NSFC)
  (Grants No. 22209034). M.C. received funding from the European Union's Horizon 2020
  research and innovation program under the Marie Skłodowska-Curie Grant Agreement
  No. 665385.
article_number: e202402628
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Christine
  full_name: Fiedler, Christine
  id: bd3fceba-dc74-11ea-a0a7-c17f71817366
  last_name: Fiedler
- first_name: Mariano
  full_name: Calcabrini, Mariano
  id: 45D7531A-F248-11E8-B48F-1D18A9856A87
  last_name: Calcabrini
  orcid: 0000-0003-4566-5877
- first_name: Yu
  full_name: Liu, Yu
  id: 2A70014E-F248-11E8-B48F-1D18A9856A87
  last_name: Liu
  orcid: 0000-0001-7313-6740
- first_name: Maria
  full_name: Ibáñez, Maria
  id: 43C61214-F248-11E8-B48F-1D18A9856A87
  last_name: Ibáñez
  orcid: 0000-0001-5013-2843
citation:
  ama: Fiedler C, Calcabrini M, Liu Y, Ibáñez M. Unveiling crucial chemical processing
    parameters influencing the performance of solution-processed inorganic thermoelectric
    materials. <i>Angewandte Chemie International Edition</i>. 2024;63(25). doi:<a
    href="https://doi.org/10.1002/anie.202402628">10.1002/anie.202402628</a>
  apa: Fiedler, C., Calcabrini, M., Liu, Y., &#38; Ibáñez, M. (2024). Unveiling crucial
    chemical processing parameters influencing the performance of solution-processed
    inorganic thermoelectric materials. <i>Angewandte Chemie International Edition</i>.
    Wiley. <a href="https://doi.org/10.1002/anie.202402628">https://doi.org/10.1002/anie.202402628</a>
  chicago: Fiedler, Christine, Mariano Calcabrini, Yu Liu, and Maria Ibáñez. “Unveiling
    Crucial Chemical Processing Parameters Influencing the Performance of Solution-Processed
    Inorganic Thermoelectric Materials.” <i>Angewandte Chemie International Edition</i>.
    Wiley, 2024. <a href="https://doi.org/10.1002/anie.202402628">https://doi.org/10.1002/anie.202402628</a>.
  ieee: C. Fiedler, M. Calcabrini, Y. Liu, and M. Ibáñez, “Unveiling crucial chemical
    processing parameters influencing the performance of solution-processed inorganic
    thermoelectric materials,” <i>Angewandte Chemie International Edition</i>, vol.
    63, no. 25. Wiley, 2024.
  ista: Fiedler C, Calcabrini M, Liu Y, Ibáñez M. 2024. Unveiling crucial chemical
    processing parameters influencing the performance of solution-processed inorganic
    thermoelectric materials. Angewandte Chemie International Edition. 63(25), e202402628.
  mla: Fiedler, Christine, et al. “Unveiling Crucial Chemical Processing Parameters
    Influencing the Performance of Solution-Processed Inorganic Thermoelectric Materials.”
    <i>Angewandte Chemie International Edition</i>, vol. 63, no. 25, e202402628, Wiley,
    2024, doi:<a href="https://doi.org/10.1002/anie.202402628">10.1002/anie.202402628</a>.
  short: C. Fiedler, M. Calcabrini, Y. Liu, M. Ibáñez, Angewandte Chemie International
    Edition 63 (2024).
corr_author: '1'
das_tickbox: '1'
date_created: 2024-05-26T22:00:58Z
date_published: 2024-06-17T00:00:00Z
date_updated: 2026-07-08T05:53:04Z
day: '17'
ddc:
- '540'
department:
- _id: MaIb
doi: 10.1002/anie.202402628
ec_funded: 1
external_id:
  isi:
  - '001223768400001'
  pmid:
  - '38623865'
file:
- access_level: open_access
  checksum: 1572a0f4d2df55751761efeb2d11c7fc
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-09T09:12:07Z
  date_updated: 2025-01-09T09:12:07Z
  file_id: '18797'
  file_name: 2024_AngewChemieIntern_Fiedler.pdf
  file_size: 16347226
  relation: main_file
  success: 1
file_date_updated: 2025-01-09T09:12:07Z
has_accepted_license: '1'
intvolume: '        63'
isi: 1
issue: '25'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 9B8F7476-BA93-11EA-9121-9846C619BF3A
  name: 'HighTE: The Werner Siemens Laboratory for the High Throughput Discovery of
    Semiconductors for Waste Heat Recovery'
publication: Angewandte Chemie International Edition
publication_identifier:
  eissn:
  - 1521-3773
  issn:
  - 1433-7851
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Unveiling crucial chemical processing parameters influencing the performance
  of solution-processed inorganic thermoelectric materials
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 63
year: '2024'
...
---
_id: '15182'
abstract:
- lang: eng
  text: Thermoelectric materials convert heat into electricity, with a broad range
    of applications near room temperature (RT). However, the library of RT high-performance
    materials is limited. Traditional high-temperature synthetic methods constrain
    the range of materials achievable, hindering the ability to surpass crystal structure
    limitations and engineer defects. Here, a solution-based synthetic approach is
    introduced, enabling RT synthesis of powders and exploration of densification
    at lower temperatures to influence the material's microstructure. The approach
    is exemplified by Ag2Se, an n-type alternative to bismuth telluride. It is demonstrated
    that the concentration of Ag interstitials, grain boundaries, and dislocations
    are directly correlated to the sintering temperature, and achieve a figure of
    merit of 1.1 from RT to 100 °C after optimization. Moreover, insights into and
    resolve Ag2Se's challenges are provided, including stoichiometry issues leading
    to irreproducible performances. This work highlights the potential of RT solution
    synthesis in expanding the repertoire of high-performance thermoelectric materials
    for practical applications.
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: NanoFab
acknowledgement: This work was supported by the Scientific Service Units (SSU) of
  ISTA through resources provided by the Electron Microscopy Facility (EMF), the Lab
  Support Facility (LSF), and the Nanofabrication Facility (NNF). This work was financially
  supported by ISTA and the Werner Siemens Foundation. The USTEM Service Unit of the
  Technical University of Vienna is acknowledged for EBSD sample preparation and analysis.
  R.L.B. acknowledges the National Science Foundation for funding the mass spectrometry
  analysis under award DMR 1904719. J.L. is a Serra Húnter Fellow and is grateful
  to the ICREA Academia program and projects MICINN/FEDER PID2021-124572OB-C31 and
  GC 2021 SGR 01061.
article_number: '2400408'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Tobias
  full_name: Kleinhanns, Tobias
  id: 8BD9DE16-AB3C-11E9-9C8C-2A03E6697425
  last_name: Kleinhanns
  orcid: 0000-0003-1537-7436
- first_name: Francesco
  full_name: Milillo, Francesco
  id: 38b830db-ea88-11ee-bf9b-929beaf79054
  last_name: Milillo
- first_name: Mariano
  full_name: Calcabrini, Mariano
  id: 45D7531A-F248-11E8-B48F-1D18A9856A87
  last_name: Calcabrini
  orcid: 0000-0003-4566-5877
- first_name: Christine
  full_name: Fiedler, Christine
  id: bd3fceba-dc74-11ea-a0a7-c17f71817366
  last_name: Fiedler
- first_name: Sharona
  full_name: Horta, Sharona
  id: 03a7e858-01b1-11ec-8b71-99ae6c4a05bc
  last_name: Horta
- first_name: Daniel
  full_name: Balazs, Daniel
  id: 302BADF6-85FC-11EA-9E3B-B9493DDC885E
  last_name: Balazs
  orcid: 0000-0001-7597-043X
- first_name: Marissa J.
  full_name: Strumolo, Marissa J.
  last_name: Strumolo
- first_name: Roger
  full_name: Hasler, Roger
  last_name: Hasler
- first_name: Jordi
  full_name: Llorca, Jordi
  last_name: Llorca
- first_name: Michael
  full_name: Tkadletz, Michael
  last_name: Tkadletz
- first_name: Richard L.
  full_name: Brutchey, Richard L.
  last_name: Brutchey
- first_name: Maria
  full_name: Ibáñez, Maria
  id: 43C61214-F248-11E8-B48F-1D18A9856A87
  last_name: Ibáñez
  orcid: 0000-0001-5013-2843
citation:
  ama: 'Kleinhanns T, Milillo F, Calcabrini M, et al. A route to high thermoelectric
    performance: Solution‐based control of microstructure and composition in Ag2Se.
    <i>Advanced Energy Materials</i>. 2024;14(22). doi:<a href="https://doi.org/10.1002/aenm.202400408">10.1002/aenm.202400408</a>'
  apa: 'Kleinhanns, T., Milillo, F., Calcabrini, M., Fiedler, C., Horta, S., Balazs,
    D., … Ibáñez, M. (2024). A route to high thermoelectric performance: Solution‐based
    control of microstructure and composition in Ag2Se. <i>Advanced Energy Materials</i>.
    Wiley. <a href="https://doi.org/10.1002/aenm.202400408">https://doi.org/10.1002/aenm.202400408</a>'
  chicago: 'Kleinhanns, Tobias, Francesco Milillo, Mariano Calcabrini, Christine Fiedler,
    Sharona Horta, Daniel Balazs, Marissa J. Strumolo, et al. “A Route to High Thermoelectric
    Performance: Solution‐based Control of Microstructure and Composition in Ag2Se.”
    <i>Advanced Energy Materials</i>. Wiley, 2024. <a href="https://doi.org/10.1002/aenm.202400408">https://doi.org/10.1002/aenm.202400408</a>.'
  ieee: 'T. Kleinhanns <i>et al.</i>, “A route to high thermoelectric performance:
    Solution‐based control of microstructure and composition in Ag2Se,” <i>Advanced
    Energy Materials</i>, vol. 14, no. 22. Wiley, 2024.'
  ista: 'Kleinhanns T, Milillo F, Calcabrini M, Fiedler C, Horta S, Balazs D, Strumolo
    MJ, Hasler R, Llorca J, Tkadletz M, Brutchey RL, Ibáñez M. 2024. A route to high
    thermoelectric performance: Solution‐based control of microstructure and composition
    in Ag2Se. Advanced Energy Materials. 14(22), 2400408.'
  mla: 'Kleinhanns, Tobias, et al. “A Route to High Thermoelectric Performance: Solution‐based
    Control of Microstructure and Composition in Ag2Se.” <i>Advanced Energy Materials</i>,
    vol. 14, no. 22, 2400408, Wiley, 2024, doi:<a href="https://doi.org/10.1002/aenm.202400408">10.1002/aenm.202400408</a>.'
  short: T. Kleinhanns, F. Milillo, M. Calcabrini, C. Fiedler, S. Horta, D. Balazs,
    M.J. Strumolo, R. Hasler, J. Llorca, M. Tkadletz, R.L. Brutchey, M. Ibáñez, Advanced
    Energy Materials 14 (2024).
corr_author: '1'
date_created: 2024-03-25T08:57:40Z
date_published: 2024-06-12T00:00:00Z
date_updated: 2026-07-17T07:09:41Z
day: '12'
ddc:
- '530'
department:
- _id: MaIb
- _id: LifeSc
doi: 10.1002/aenm.202400408
external_id:
  isi:
  - '001184300200001'
file:
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  file_size: 8824301
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  success: 1
file_date_updated: 2024-07-22T12:07:56Z
has_accepted_license: '1'
intvolume: '        14'
isi: 1
issue: '22'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 9B8F7476-BA93-11EA-9121-9846C619BF3A
  name: 'HighTE: The Werner Siemens Laboratory for the High Throughput Discovery of
    Semiconductors for Waste Heat Recovery'
publication: Advanced Energy Materials
publication_identifier:
  eissn:
  - 1614-6840
  issn:
  - 1614-6832
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
  record:
  - id: '22017'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: 'A route to high thermoelectric performance: Solution‐based control of microstructure
  and composition in Ag2Se'
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: 14
year: '2024'
...
---
OA_place: publisher
_id: '18477'
abstract:
- lang: eng
  text: "ADAR1 is broadly expressed across various tissues and is vital in regulating
    pathways\r\nassociated with innate immune responses. ADAR1 marks double-stranded
    RNA as \"self\"\r\nthrough its A-to-I editing activity, effectively repressing
    autoimmunity and maintaining\r\nimmune tolerance. This editing process has been
    detected at millions of sites across the\r\nhuman genome. However, the mechanism
    underlying ADAR1's substrate selectivity\r\nproperties remains largely unclear,
    with much of the current knowledge derived from\r\ncomparisons to its more extensively
    studied homolog, ADAR2. By studying ADAR1 in complex\r\nwith its RNA substrates
    and applying a combination of biochemical techniques and structural\r\nstudies
    using CryoEM, we aim to gain a more comprehensive understanding of the substrate\r\nselectivity
    characteristics of ADAR1.\r\nIn this thesis, the purification protocol for ADAR1
    was successfully optimized, resulting in the\r\nfirst report in the literature
    to achieve high protein purity and activity. This advancement\r\nenabled the investigation
    of complex formation between ADAR1 and various RNA substrates,\r\nleading to the
    identification of optimal conditions for preparing the cryoEM sample. However,\r\ndespite
    comprehensive optimization of the cryo-EM conditions, the resulting data lacked
    the\r\ndesired quality, highlighting the need for similar rigorous optimization
    of the RNA substrates\r\nto facilitate structural studies of the ADAR1-RNA complex.
    The study was complemented by\r\nAlphaFold predictions, which provided some insights
    into this mechanism.\r\nMoreover, during this project I established a collaboration
    with a research group focused on\r\nstudying ADAR homologs. Notably ADAR homologs
    were identified in bivalve species, and it\r\nwas further demonstrated that ADAR
    and its A-to-I editing activity are upregulated in Pacific\r\noysters during infections
    with Ostreid herpesvirus-1—a highly infectious virus that leads to\r\nsignificant
    losses in oyster populations globally. I successfully purified oyster ADAR and\r\nprepared
    in vitro edited RNA for nanopore sequencing—a direct sequencing technology\r\ncapable
    of detecting modified nucleotides without the need for reverse transcription.
    The\r\ncollaborators initiated optimization of this nanopore-based approach. However,
    current\r\ntechnological limitations still constrain the reliable detection of
    modified nucleotides.\r\nThe project also examined the impact of RNA editing on
    RNA binding and filament formation\r\nby MDA5, a key cytosolic dsRNA sensor that
    triggers an interferon response. A primary target\r\nof ADAR1's editing activity
    is RNA derived from repetitive elements present in the genome,\r\nparticularly
    Alu elements forming double-stranded RNA. When unedited, these RNA\r\nsequences
    are recognized by MDA5. However, the mechanisms by which MDA5 interacts with\r\nAlu
    RNAs, as well as the role of A-to-I editing in influencing this binding, are still
    not well\r\nunderstood.\r\nThe interaction between MDA5 and Alu elements, was
    successfully established. This was\r\nachieved through the testing of different
    RNA variants and the evaluation of filament\r\nformation using binding techniques
    and electron microscopy imaging. This groundwork has\r\nset the conditions for
    further evaluation using CryoEM. Furthermore, the effects of A-to-I\r\nediting
    on the binding properties of MDA5 with Alu RNA were investigated. Given the recent\r\nresearch
    that has provided new insights into MDA5's interaction with dsRNA, it is essential
    to\r\nrevise the experimental setup to integrate these findings before moving
    forward with the\r\nCryoEM sample analysis."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Beata M
  full_name: Kaczmarek, Beata M
  id: 36FA4AFA-F248-11E8-B48F-1D18A9856A87
  last_name: Kaczmarek
citation:
  ama: Kaczmarek BM. Biochemical and structural insights into ADAR1 RNA editing. 2024.
    doi:<a href="https://doi.org/10.15479/at:ista:18477">10.15479/at:ista:18477</a>
  apa: Kaczmarek, B. M. (2024). <i>Biochemical and structural insights into ADAR1
    RNA editing</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18477">https://doi.org/10.15479/at:ista:18477</a>
  chicago: Kaczmarek, Beata M. “Biochemical and Structural Insights into ADAR1 RNA
    Editing.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18477">https://doi.org/10.15479/at:ista:18477</a>.
  ieee: B. M. Kaczmarek, “Biochemical and structural insights into ADAR1 RNA editing,”
    Institute of Science and Technology Austria, 2024.
  ista: Kaczmarek BM. 2024. Biochemical and structural insights into ADAR1 RNA editing.
    Institute of Science and Technology Austria.
  mla: Kaczmarek, Beata M. <i>Biochemical and Structural Insights into ADAR1 RNA Editing</i>.
    Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18477">10.15479/at:ista:18477</a>.
  short: B.M. Kaczmarek, Biochemical and Structural Insights into ADAR1 RNA Editing,
    Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-10-27T07:35:13Z
date_published: 2024-10-29T00:00:00Z
date_updated: 2026-04-07T13:23:59Z
day: '29'
ddc:
- '572'
degree_awarded: PhD
department:
- _id: GradSch
- _id: CaBe
doi: 10.15479/at:ista:18477
file:
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file_date_updated: 2025-10-29T23:30:02Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '124'
publication_identifier:
  isbn:
  - 978-3-99078-045-9
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
title: Biochemical and structural insights into ADAR1 RNA editing
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '15352'
abstract:
- lang: eng
  text: "Epilepsy affects about 50 to 65 million people globally. It summarizes a
    spectrum of neurological\r\ndisorders that have in common a hyperactivity of the
    neuronal network resulting in seizures. A common\r\nassumption is that an imbalance
    between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation
    and epileptogeneisis. In at least one-third of the patients, current therapies
    have\r\nproven unsuccessful in treating seizure progression. One potential reason
    could be that the therapies\r\nonly focus on neurons. Recent studies suggest that
    neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain
    homeostasis. Additionally, interactions between microglia and neurons\r\nhave
    been shown to inhibit neuronal firing and dampen seizure activity. However, the
    exact relationship\r\nbetween microglia and seizure progression in epilepsy is
    yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate
    microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia
    dynamics due to their rapid response to environmental changes. On the other hand,
    in vivo\r\nstudies focus mostly on behavior characterization of the epileptic
    seizure phenotype and their long-term\r\nconsequences on microglia activity leaving
    out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere,
    we perform a pilot study to combine electroencephalography (EEG) and in vivo live
    imaging to\r\ndirectly monitor and correlate the onset of seizure activity with
    microglia response. To induce seizures,\r\nwe take advantage of the kainic acid
    (KA) model, which represents similar neuropathological and\r\nelectroencephalographic
    features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation
    of induction of the seizure and microglia activity in the hippocampus as a focal
    point, we\r\ninvestigated whether these changes also reached the primary visual
    cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that
    microglia changed their morphology at high doses\r\nof KA in the V1. Next, we
    optimized each of the two methodological components: for the EEG recording,\r\nour
    initial attempts under the microscope suffered from extensive electrical noise,
    which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage
    and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be
    able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia,
    we had to optimize the imaging parameters, so that we would be able to detect
    microglial\r\nprocesses in a sufficient resolution to track their process changes.
    Finally, we combined both\r\nmethodologies with the KA model. We confirmed that
    KA induced seizure activity and found first\r\nindication that those correlate
    with microglia volume changes.\r\nOverall, we have developed a first methodological
    approach, which allows the analysis of the acute\r\neffects of seizure onset on
    microglia. Future studies will have to continue to optimize the drift during\r\nimaging
    recording and the post-image analysis. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
alternative_title:
- ISTA Master's Thesis
article_processing_charge: No
author:
- first_name: Julie Stefanie
  full_name: Murmann, Julie Stefanie
  id: 1d390868-f128-11eb-9611-a0ca5f7833b5
  last_name: Murmann
citation:
  ama: 'Murmann JS. Investigating acute microglia response to seizure activity in
    vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:<a href="https://doi.org/10.15479/at:ista:15352">10.15479/at:ista:15352</a>'
  apa: 'Murmann, J. S. (2024). <i>Investigating acute microglia response to seizure
    activity in vivo: Combining 2-Photon imaging and EEG recording</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:15352">https://doi.org/10.15479/at:ista:15352</a>'
  chicago: 'Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure
    Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of
    Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:15352">https://doi.org/10.15479/at:ista:15352</a>.'
  ieee: 'J. S. Murmann, “Investigating acute microglia response to seizure activity
    in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and
    Technology Austria, 2024.'
  ista: 'Murmann JS. 2024. Investigating acute microglia response to seizure activity
    in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and
    Technology Austria.'
  mla: 'Murmann, Julie Stefanie. <i>Investigating Acute Microglia Response to Seizure
    Activity in Vivo: Combining 2-Photon Imaging and EEG Recording</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:15352">10.15479/at:ista:15352</a>.'
  short: 'J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity
    in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and
    Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-05-02T08:31:38Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-07T13:05:00Z
day: '02'
ddc:
- '570'
degree_awarded: MS
department:
- _id: SaSi
- _id: GradSch
doi: 10.15479/at:ista:15352
file:
- access_level: open_access
  checksum: 095817a6c944954ac3f277e547031a33
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  creator: cchlebak
  date_created: 2024-05-02T12:26:13Z
  date_updated: 2025-05-02T22:30:04Z
  embargo: 2025-05-02
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  file_name: Murmann_Thesis_final_2024_2.pdf
  file_size: 5936142
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  checksum: 43b632255372973a437ac87739cfd4db
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  creator: cchlebak
  date_created: 2024-05-02T12:37:56Z
  date_updated: 2025-05-02T22:30:04Z
  embargo_to: open_access
  file_id: '15355'
  file_name: Murmann_Thesis_final_2024.zip
  file_size: 20645510
  relation: source_file
file_date_updated: 2025-05-02T22:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '54'
publication_identifier:
  issn:
  - 2791-4585
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
title: 'Investigating acute microglia response to seizure activity in vivo: Combining
  2-Photon imaging and EEG recording'
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '18471'
abstract:
- lang: eng
  text: "Spatial omics technologies are enriching our understanding of complex biological
    samples, by\r\nallowing us to study their molecular composition while preserving
    the spatial relationships\r\nbetween molecules in their native context. As the
    field continues to advance, there are\r\ntechnical challenges that need to be
    addressed in order to take full advantage of the spatial\r\ncapabilities of these
    methods. In this work, I present two technical developments that I\r\nestablished
    for multiplexed error robust FISH (MERFISH) throughout my PhD: (1) pushing the\r\nspatial
    resolution limits to the nanoscale, and (2) adding rich tissue context to the
    mouse brain\r\ntranscriptome. To achieve nanoscale resolution with MERFISH in
    cultured cells, I combined it\r\nwith stimulated emission depletion (STED) and
    expansion microscopy (ExM) to achieve a\r\nspatial resolution as low as ~20 nm,
    and explored the compatibility of MERFISH with singlemolecule localization microscopy
    (SMLM) techniques. To visualize targeted mRNAs in mouse\r\nbrain tissue, I applied
    the comprehensive analysis of tissues across scales (CATS) toolbox, which\r\nprovides
    an unbiased morphological readout by labeling the extracellular domain. I\r\nsuccessfully
    established this method, which we call CATS-MERFISH-ExM, to work with thick\r\nmouse
    brain slices, being able to extract transcriptomics information with 3D tissue
    context.\r\nCATS-MERFISH-ExM enabled us to identify cell types and further visualize
    the subcellular\r\ndistribution of transcripts in mouse brain tissue, shedding
    light on the neuropil-specific\r\ntranscriptome. This method provides integrated
    information on cellular structure and\r\ntranscriptomes in situ, and could potentially
    be applied with other modalities, opening new\r\navenues for scientific discovery. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
- _id: M-Shop
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
citation:
  ama: Agudelo Duenas N. Visualizing the neuronal transcriptional landscape with tissue
    context. 2024. doi:<a href="https://doi.org/10.15479/at:ista:18471">10.15479/at:ista:18471</a>
  apa: Agudelo Duenas, N. (2024). <i>Visualizing the neuronal transcriptional landscape
    with tissue context</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18471">https://doi.org/10.15479/at:ista:18471</a>
  chicago: Agudelo Duenas, Nathalie. “Visualizing the Neuronal Transcriptional Landscape
    with Tissue Context.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18471">https://doi.org/10.15479/at:ista:18471</a>.
  ieee: N. Agudelo Duenas, “Visualizing the neuronal transcriptional landscape with
    tissue context,” Institute of Science and Technology Austria, 2024.
  ista: Agudelo Duenas N. 2024. Visualizing the neuronal transcriptional landscape
    with tissue context. Institute of Science and Technology Austria.
  mla: Agudelo Duenas, Nathalie. <i>Visualizing the Neuronal Transcriptional Landscape
    with Tissue Context</i>. Institute of Science and Technology Austria, 2024, doi:<a
    href="https://doi.org/10.15479/at:ista:18471">10.15479/at:ista:18471</a>.
  short: N. Agudelo Duenas, Visualizing the Neuronal Transcriptional Landscape with
    Tissue Context, Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-10-26T20:02:42Z
date_published: 2024-10-28T00:00:00Z
date_updated: 2026-04-14T08:34:37Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoDa
doi: 10.15479/at:ista:18471
ec_funded: 1
file:
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file_date_updated: 2025-05-05T22:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '97'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
publication_identifier:
  isbn:
  - 978-3-99078-044-2
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
title: Visualizing the neuronal transcriptional landscape with tissue context
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_embargo: '12'
OA_place: publisher
_id: '18574'
abstract:
- lang: eng
  text: "Biological vision is unlike a camera; rather than transmitting light information
    faithfully, early\r\nvisual circuits process the visual scene to convey only the
    relevant information in an efficient\r\nmanner. Consequentially, the nature of
    this visual processing then depends on what is the\r\nrelevant information in
    a scene and on the notion of efficiency. In this work, I study how visual\r\nprocessing
    is modulated by two different variations in the visual scene. First, I discovered
    that\r\nin the mouse (Mus musculus) retina, Retinal Ganglion Cells in the upper
    and lower visual\r\nfield have differences in the center surround structure of
    their receptive fields. Comparison\r\nwith models of efficient coding show that
    this adaptation likely evolved to cope with the\r\nbrightness gradient from the
    sky to the ground that is pervasive in natural scenes. In the\r\nsecond project,
    I study how the downstream neurons in the Superior Colliculus dynamically\r\nchange
    their temporal selectivity depending on the ambient luminance and behavioral state.\r\nAs
    the scene gets darker or when the animal is is less aroused, the neuronal responses
    get\r\nlaggier, while still maintaining their relative timing with respect to
    the population. Overall, this\r\nwork emphasises the need to understand visual
    processing in the context of specific demands\r\nof the animal in its the environment.
    The adaptive changes in the visual system, from the\r\nretinal ganglion cells
    to the superior colliculus, highlight the intricate ways in which biological\r\nvision
    optimizes the processing of visual information.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: ScienComp
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "This work would have been impossible without the Scientific Service
  Units of IST Austria. The resources and expertise provided by Scientific Computing
  (especially Alois Schlögl), the MIBA Machine Shop (especially Todor Asenov), the
  Preclinical Facility (especially Freyja Langer), the Library, the Lab Support Facility
  and the Imaging and Optics Facility were the essential bedrock I could build upon.
  I would also like to thank IT support at ISTA for powering through remote work and
  a cyberattack.\r\nI am grateful for having been funded initially by the European
  Union Horizon 2020 Marie Skłodowska-Curie grant 665385 and later by Prof. Maximilian
  Joesch's the European Research Council Starting (756502) and Consolidator (101086580)
  Grants."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Divyansh
  full_name: Gupta, Divyansh
  id: 2A485EBE-F248-11E8-B48F-1D18A9856A87
  last_name: Gupta
  orcid: 0000-0001-7400-6665
citation:
  ama: Gupta D. Visual adaptations to natural statistics. 2024. doi:<a href="https://doi.org/10.15479/at:ista:18574">10.15479/at:ista:18574</a>
  apa: Gupta, D. (2024). <i>Visual adaptations to natural statistics</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18574">https://doi.org/10.15479/at:ista:18574</a>
  chicago: Gupta, Divyansh. “Visual Adaptations to Natural Statistics.” Institute
    of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18574">https://doi.org/10.15479/at:ista:18574</a>.
  ieee: D. Gupta, “Visual adaptations to natural statistics,” Institute of Science
    and Technology Austria, 2024.
  ista: Gupta D. 2024. Visual adaptations to natural statistics. Institute of Science
    and Technology Austria.
  mla: Gupta, Divyansh. <i>Visual Adaptations to Natural Statistics</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18574">10.15479/at:ista:18574</a>.
  short: D. Gupta, Visual Adaptations to Natural Statistics, Institute of Science
    and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-11-20T21:30:44Z
date_published: 2024-11-22T00:00:00Z
date_updated: 2026-04-07T13:24:48Z
day: '22'
ddc:
- '573'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MaJö
doi: 10.15479/at:ista:18574
ec_funded: 1
file:
- access_level: closed
  checksum: ebb000d361c36b22ed6e639a931c6b7c
  content_type: application/zip
  creator: dgupta
  date_created: 2024-11-25T14:44:03Z
  date_updated: 2025-11-11T23:30:02Z
  embargo_to: open_access
  file_id: '18589'
  file_name: PhD Thesis - Divyansh Gupta.zip
  file_size: 75512262
  relation: source_file
- access_level: open_access
  checksum: 1282401eb71598bc311058b0fcefc6a1
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  creator: dgupta
  date_created: 2024-11-26T11:43:19Z
  date_updated: 2025-11-11T23:30:02Z
  embargo: 2025-11-11
  file_id: '18591'
  file_name: PDFA_PhD_Thesis___Divyansh_Gupta-26_11_24.pdf
  file_size: 6412619
  relation: main_file
file_date_updated: 2025-11-11T23:30:02Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '11'
oa: 1
oa_version: Published Version
page: '86'
project:
- _id: bdaf81a8-d553-11ed-ba76-c95961984540
  grant_number: '101086580'
  name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
publication_identifier:
  isbn:
  - 978-3-99078-050-3
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '12349'
    relation: part_of_dissertation
    status: public
  - id: '12370'
    relation: research_data
    status: public
status: public
supervisor:
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
title: Visual adaptations to natural statistics
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
_id: '15323'
abstract:
- lang: eng
  text: Supercomplexes of the respiratory chain are established constituents of the
    oxidative phosphorylation system, but their role in mammalian metabolism has been
    hotly debated. Although recent studies have shown that different tissues/organs
    are equipped with specific sets of supercomplexes, depending on their metabolic
    needs, the notion that supercomplexes have a role in the regulation of metabolism
    has been challenged. However, irrespective of the mechanistic conclusions, the
    composition of various high molecular weight supercomplexes remains uncertain.
    Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse)
    tissues contain three defined types of ‘respirasome’, supercomplexes made of CI,
    CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes,
    of which only one contains the supercomplex-associated factor SCAF1, whose involvement
    in respirasome formation has long been contended. Our structures confirm that
    the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1,
    which is instead associated to a different respirasome (the CS-respirasome), containing
    a second copy of CIV. We also identify an alternative respirasome (A-respirasome),
    with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization
    of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis
    for their specific role in different metabolic conditions.
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: PreCl
- _id: ScienComp
acknowledgement: Supercomplexes of the respiratory chain are established constituents
  of the oxidative phosphorylation system, but their role in mammalian metabolism
  has been hotly debated. Although recent studies have shown that different tissues/organs
  are equipped with specific sets of supercomplexes, depending on their metabolic
  needs, the notion that supercomplexes have a role in the regulation of metabolism
  has been challenged. However, irrespective of the mechanistic conclusions, the composition
  of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic
  electron microscopy, we demonstrate that mammalian (mouse) tissues contain three
  defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry
  and position of CIV differs in the three respirasomes, of which only one contains
  the supercomplex-associated factor SCAF1, whose involvement in respirasome formation
  has long been contended. Our structures confirm that the ‘canonical’ respirasome
  (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated
  to a different respirasome (the CS-respirasome), containing a second copy of CIV.
  We also identify an alternative respirasome (A-respirasome), with CIV bound to the
  ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial
  supercomplexes allows us to hypothesize a mechanistic basis for their specific role
  in different metabolic conditions.
article_processing_charge: No
article_type: original
author:
- first_name: Irene
  full_name: Vercellino, Irene
  id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
  last_name: Vercellino
  orcid: 0000-0001-5618-3449
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
citation:
  ama: Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian
    respirasomes. <i>Nature Structural and Molecular Biology</i>. 2024;31:1061-1071.
    doi:<a href="https://doi.org/10.1038/s41594-024-01255-0">10.1038/s41594-024-01255-0</a>
  apa: Vercellino, I., &#38; Sazanov, L. A. (2024). SCAF1 drives the compositional
    diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41594-024-01255-0">https://doi.org/10.1038/s41594-024-01255-0</a>
  chicago: Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional
    Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>.
    Springer Nature, 2024. <a href="https://doi.org/10.1038/s41594-024-01255-0">https://doi.org/10.1038/s41594-024-01255-0</a>.
  ieee: I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity
    of mammalian respirasomes,” <i>Nature Structural and Molecular Biology</i>, vol.
    31. Springer Nature, pp. 1061–1071, 2024.
  ista: Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of
    mammalian respirasomes. Nature Structural and Molecular Biology. 31, 1061–1071.
  mla: Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity
    of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>, vol.
    31, Springer Nature, 2024, pp. 1061–71, doi:<a href="https://doi.org/10.1038/s41594-024-01255-0">10.1038/s41594-024-01255-0</a>.
  short: I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology 31 (2024)
    1061–1071.
corr_author: '1'
date_created: 2024-04-14T22:01:03Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2025-11-24T08:35:04Z
day: '01'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41594-024-01255-0
ec_funded: 1
external_id:
  isi:
  - '001196897300001'
  pmid:
  - '38575788'
file:
- access_level: open_access
  checksum: 21f05d188762acd7f49a97f3d09c8d9f
  content_type: application/pdf
  creator: lsazanov
  date_created: 2024-05-14T11:57:56Z
  date_updated: 2025-01-01T23:30:03Z
  embargo: 2025-01-01
  file_id: '15392'
  file_name: megacomplex_submit_NSMB_withFigures.pdf
  file_size: 24424729
  relation: main_file
file_date_updated: 2025-01-01T23:30:03Z
has_accepted_license: '1'
intvolume: '        31'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Submitted Version
page: 1061-1071
pmid: 1
project:
- _id: 627abdeb-2b32-11ec-9570-ec31a97243d3
  call_identifier: H2020
  grant_number: '101020697'
  name: Structure and mechanism of respiratory chain molecular machines
publication: Nature Structural and Molecular Biology
publication_identifier:
  eissn:
  - 1545-9985
  issn:
  - 1545-9993
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41594-025-01721-3
scopus_import: '1'
status: public
title: SCAF1 drives the compositional diversity of mammalian respirasomes
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: 31
year: '2024'
...
---
OA_place: publisher
_id: '18101'
abstract:
- lang: eng
  text: "The Retroviridae family consists of two sub-families, the Orthoretrovirinae
    and the\r\nSpumaretrovirinae. The Orthoretroviruses contain important human pathogens,
    such as the\r\nhuman immunodeficiency virus 1 (HIV-1). They also harbor other
    retrovirus species which\r\nare regularly used as model systems to study the retroviral
    life cycle. The main structural\r\ncomponent of the retroviruses, is the Gag protein
    and its truncation derivatives occurring\r\nduring viral maturation. Orthoretroviral
    Gag assemblies have been extensively studied to\r\nunderstand the interactions
    that confer stability and morphology to viral particles.\r\nThe Spumaretrovirinae
    subfamily represent an early diverging branch of the Retroviridae.\r\nIts members,
    the Foamy viruses (FV), share most of the conventional features found in\r\nretroviruses.
    However, they also possess multiple characteristics that make them unique. In\r\nparticular,
    FV Gag does not get extensively cleaved as in orthoretroviruses. Hence, the Gag\r\narchitecture
    deviates from the canonical domain arrangement in FV. They also exhibit a\r\npeculiar
    particle morphology, having no apparent immature state and a seemingly\r\nicosahedral
    mature particle. Due to this, many fundamental questions on FV structural\r\nassembly
    mechanisms remain open. To answer these questions, was the main focus of this\r\nthesis.\r\nMainly,
    it is not known how FV assemble their core in a virus particle and what are the\r\nimportant
    assembly interaction sites within said core. What is the minimum assembly\r\ncompetent
    domain of FV Gag? Is there a morphological change in the assembly type of FVGag
    lattices? If so, what is defining these morphological shifts? Finally, it would
    be\r\ninteresting to know what is the evolutionary relationship between FV and
    the rest of the\r\nretrotranscribing elements, from a structural point of view?\r\nTo
    answer these questions, membrane-enveloped mammalian cell-derived FV virus-like\r\nparticles
    (VLPs) were produced. Cryo-electron tomography (cryo-ET) analysis suggested\r\nthese
    FV VLPs do not form a canonical retroviral Gag lattice structure, which is in
    line with\r\nearlier observations. To further evaluate FV Gag assembly competence
    and morphology,\r\nthe first bacterial cell-derived in vitro VLP assembly system
    was designed and optimized.\r\nUsing this system with different truncation variants,
    the minimum assembly competent\r\ndomain of FV Gag was found to be the putative
    CA300-477 domain. Varying VLP\r\nmorphologies were also observed and strongly
    suggested residues upstream of CA300-477\r\nplay a role in morphology determination.
    Finally, a combined cryo-electron microscopy (cryoEM) and cryo-ET approach was
    taken to analyze tubular assemblies from the minimal\r\nassembly competent domain.
    This revealed an unexpectedly unique non-canonical\r\nassembly architecture. Three
    novel lattice stabilizing interfaces were described which\r\nproved to be as unique
    as the lattice arrangement. Comparison to a newly published FV CA\r\ncore structure
    revealed the CA-CA interactions in the atypical assembly do not recapitulate\r\nwhat
    is described for the FV core lattice. However, the new in vitro VLP assembly system\r\nobtained
    in this thesis also provides an exciting opportunity to study still unresolved
    FV\r\nassembly features in a potentially facilitated approach compared to conventional
    methods.\r\nIn summary, this work provided a deeper understanding of the basic
    FV Gag assembly unit,\r\nas well as presenting the first FV Gag-derived in vitro
    VLP assembly system. This system\r\nreveals a novel and unique assembly architecture
    among retroviral in vitro assemblies."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dario J
  full_name: Porley, Dario J
  id: 2FD6EA6C-F248-11E8-B48F-1D18A9856A87
  last_name: Porley
citation:
  ama: Porley Esteves D. Structural characterization of spumavirus capsid assemblies.
    2024. doi:<a href="https://doi.org/10.15479/at:ista:18101">10.15479/at:ista:18101</a>
  apa: Porley Esteves, D. (2024). <i>Structural characterization of spumavirus capsid
    assemblies</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18101">https://doi.org/10.15479/at:ista:18101</a>
  chicago: Porley Esteves, Darío. “Structural Characterization of Spumavirus Capsid
    Assemblies.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18101">https://doi.org/10.15479/at:ista:18101</a>.
  ieee: D. Porley Esteves, “Structural characterization of spumavirus capsid assemblies,”
    Institute of Science and Technology Austria, 2024.
  ista: Porley Esteves D. 2024. Structural characterization of spumavirus capsid assemblies.
    Institute of Science and Technology Austria.
  mla: Porley Esteves, Darío. <i>Structural Characterization of Spumavirus Capsid
    Assemblies</i>. Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18101">10.15479/at:ista:18101</a>.
  short: D. Porley Esteves, Structural Characterization of Spumavirus Capsid Assemblies,
    Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-09-20T10:21:03Z
date_published: 2024-09-26T00:00:00Z
date_updated: 2026-04-07T13:21:01Z
day: '26'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: FlSc
doi: 10.15479/at:ista:18101
ec_funded: 1
file:
- access_level: closed
  checksum: 3b8b0bacfe61112f3852744f3170e468
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: dporley
  date_created: 2024-09-26T13:40:33Z
  date_updated: 2025-03-25T23:30:03Z
  embargo_to: open_access
  file_id: '18149'
  file_name: PhD_thesis_DPorley_final_20240919.docx
  file_size: 14213128
  relation: source_file
- access_level: open_access
  checksum: 6c3a652a8eede874118e11d66a63652f
  content_type: application/pdf
  creator: dporley
  date_created: 2024-09-26T13:41:39Z
  date_updated: 2025-03-25T23:30:03Z
  embargo: 2025-03-25
  file_id: '18150'
  file_name: PhD_thesis_DPorley_final_20240926_pdfa1.pdf
  file_size: 18583031
  relation: main_file
file_date_updated: 2025-03-25T23:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '131'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 9B9C98E0-BA93-11EA-9121-9846C619BF3A
  grant_number: '25762'
  name: Structural characterization of spumavirus capsid assemblies to understand
    conserved Ortervirales assembly mechanisms
publication_identifier:
  isbn:
  - 978-3-99078-041-1
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
title: Structural characterization of spumavirus capsid assemblies
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '17319'
abstract:
- lang: eng
  text: "This thesis comprises two distinct projects, each offering unique insights
    into fundamental\r\ncellular processes. While distinct in their focus, these different
    perspectives have a common\r\ntheme: chemiosmotic theory and utilisation of the
    proton gradient for driving the essential\r\nprocesses like auxin efflux and ATP
    synthesis, effectively bridging the membrane protein\r\nstructure and function
    from the realms of plant biology and cellular bioenergetics.\r\nThe first project
    of this thesis centres on the characterisation of PIN proteins, a class of\r\ntransmembrane
    transporters pivotal in the regulation of auxin transport and distribution in\r\nplants.
    PINs form a conserved and phylogenetically abundant group of transporters present
    in\r\nland plants and certain algae. Despite their great importance, they were
    one of the few elusive\r\nproteins essential for plant development not to be structurally
    and mechanistically\r\ncharacterised since their discovery almost 30 years ago.
    This work aimed to uncover the\r\nstructural and functional dynamics of the PIN
    protein-mediated auxin transport using an array\r\nof experimental techniques,
    including protein purification, biochemical assays and structural\r\nanalysis.
    Through an exhaustive screening process that took several years and included testing\r\ndifferent
    PIN homologues, expression systems, constructs, and purification conditions, we\r\ndeveloped
    a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein.\r\nMoreover,
    utilising biophysical methods and buffer screening, we demonstrated that PIN8\r\nexhibits
    detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and
    6.0)\r\nbeing optimal for the stability of the protein. Using SEC-MALS and crosslinking,
    we\r\ndetermined that PIN8 forms dimers, which was confirmed by our structural
    studies. We\r\nobtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently
    published structures,\r\nour map implies major pH-dependent conformational changes
    and possibly utilisation of the\r\nproton gradient in the transport mechanism.\r\nThe
    subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental\r\nto
    cellular energy metabolism. Through an approach integrating biochemical assays
    and\r\nstructural analysis, this research aimed to unveil the molecular mechanism
    of inhibition of ATP\r\nsynthase by yaku´amide, a bioactive compound with potential
    therapeutic implications. Using\r\nsubmitochondrial particles and purified F1Fo-ATP
    synthase, we demonstrated that, contrary to\r\npublished data, yaku´amide inhibits
    both ATP hydrolysis and ATP synthesis reactions.\r\nMoreover, we found that yaku´amide
    inhibitory activity is proton motive force (pmf)\r\ndependent, with lower inhibition
    in a more coupled system. Utilising cryo-EM, we obtained\r\nmaps and models for
    the three main rotational states of murine ATP synthase (State 1 at 3.0 Å,\r\n8\r\nState
    2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in
    our maps;\r\nhowever, we cannot definitively determine the exact mechanism of
    yaku amide’s inhibition on\r\nthe protein due to either resolution limits or suboptimal
    binding of the inhibitor."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kristina
  full_name: Lukic, Kristina
  id: 2B04DB84-F248-11E8-B48F-1D18A9856A87
  last_name: Lukic
  orcid: 0000-0003-1581-881X
citation:
  ama: 'Lukic K. Membrane proteins in plant physiology and bioenergetics : Investigating
    auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor
    Yaku’amide B. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17319">10.15479/at:ista:17319</a>'
  apa: 'Lukic, K. (2024). <i>Membrane proteins in plant physiology and bioenergetics :
    Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the
    novel inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/at:ista:17319">https://doi.org/10.15479/at:ista:17319</a>'
  chicago: 'Lukic, Kristina. “Membrane Proteins in Plant Physiology and Bioenergetics :
    Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the
    Novel Inhibitor Yaku’amide B.” Institute of Science and Technology Austria, 2024.
    <a href="https://doi.org/10.15479/at:ista:17319">https://doi.org/10.15479/at:ista:17319</a>.'
  ieee: 'K. Lukic, “Membrane proteins in plant physiology and bioenergetics : Investigating
    auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor
    Yaku’amide B,” Institute of Science and Technology Austria, 2024.'
  ista: 'Lukic K. 2024. Membrane proteins in plant physiology and bioenergetics :
    Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the
    novel inhibitor Yaku’amide B. Institute of Science and Technology Austria.'
  mla: 'Lukic, Kristina. <i>Membrane Proteins in Plant Physiology and Bioenergetics :
    Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the
    Novel Inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria,
    2024, doi:<a href="https://doi.org/10.15479/at:ista:17319">10.15479/at:ista:17319</a>.'
  short: 'K. Lukic, Membrane Proteins in Plant Physiology and Bioenergetics : Investigating
    Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor
    Yaku’amide B, Institute of Science and Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-07-26T09:05:55Z
date_published: 2024-07-26T00:00:00Z
date_updated: 2026-04-07T13:20:44Z
day: '26'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: LeSa
- _id: GradSch
doi: 10.15479/at:ista:17319
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language:
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month: '07'
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oa_version: Published Version
page: '224'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
title: 'Membrane proteins in plant physiology and bioenergetics : Investigating auxin
  efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku''amide
  B'
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
