---
_id: '7680'
abstract:
- lang: eng
  text: "Proteins and their complex dynamic interactions regulate cellular mechanisms
    from sensing and transducing extracellular signals, to mediating genetic responses,
    and sustaining or changing cell morphology. To manipulate these protein-protein
    interactions (PPIs) that govern the behavior and fate of cells, synthetically
    constructed, genetically encoded tools provide the means to precisely target proteins
    of interest (POIs), and control their subcellular localization and activity in
    vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger
    that does not activate any other endogenous process, thereby allowing manipulation
    of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain
    from plants, algae and bacteria are re-purposed and genetically fused to POIs.
    Illumination with light of a specific wavelength triggers a conformational change
    that can mediate PPIs, such as dimerization or oligomerization. By using light
    as a trigger, these tools can be activated with high spatial and temporal precision,
    on subcellular and millisecond scales. Chemogenetic tools consist of protein domains
    that recognize and bind small molecules. By genetic fusion to POIs, these domains
    can mediate PPIs upon addition of their specific ligands, which are often synthetically
    designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost
    optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding
    to red, blue or near-UV light, leaving a striking gap in the green band of the
    visible light spectrum. Among both optogenetic and chemogenetic tools, there is
    an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination,
    rely on covalent linkage and subsequent enzymatic cleavage or initially result
    in protein clustering of unknown stoichiometry.\r\nThis work describes how the
    recently structurally and photochemically characterized green-light responsive
    cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed
    to function as a green-light responsive optogenetic tool. In contrast to previously
    engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI
    already upon expression, which can be rapidly disrupted by illumination. This
    was employed to mimic inhibition of constitutive activity of a growth factor receptor,
    and successfully implement for cell signalling in mammalian cells and in vivo
    to rescue development in zebrafish. This work further describes the development
    and application of a chemically induced de-dimerizer (CDD) based on a recently
    identified and structurally described bacterial oxyreductase. CDD forms a dimer
    upon expression in absence of its cofactor, the flavin derivative F420. Safety
    and of domain expression and ligand exposure are demonstrated in vitro and in
    vivo in zebrafish. The system is further applied to inhibit cell signalling output
    from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire
    of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing
    previously not utilized cues. In the future, they can readily be combined with
    existing synthetic tools to functionally manipulate PPIs in vitro and in vivo."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stephanie
  full_name: Kainrath, Stephanie
  id: 32CFBA64-F248-11E8-B48F-1D18A9856A87
  last_name: Kainrath
  orcid: 0000-0002-6709-2195
citation:
  ama: Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of
    cellular signals. 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:7680">10.15479/AT:ISTA:7680</a>
  apa: Kainrath, S. (2020). <i>Synthetic tools for optogenetic and chemogenetic inhibition
    of cellular signals</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:7680">https://doi.org/10.15479/AT:ISTA:7680</a>
  chicago: Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic
    Inhibition of Cellular Signals.” Institute of Science and Technology Austria,
    2020. <a href="https://doi.org/10.15479/AT:ISTA:7680">https://doi.org/10.15479/AT:ISTA:7680</a>.
  ieee: S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition
    of cellular signals,” Institute of Science and Technology Austria, 2020.
  ista: Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition
    of cellular signals. Institute of Science and Technology Austria.
  mla: Kainrath, Stephanie. <i>Synthetic Tools for Optogenetic and Chemogenetic Inhibition
    of Cellular Signals</i>. Institute of Science and Technology Austria, 2020, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:7680">10.15479/AT:ISTA:7680</a>.
  short: S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition
    of Cellular Signals, Institute of Science and Technology Austria, 2020.
corr_author: '1'
date_created: 2020-04-24T16:00:51Z
date_published: 2020-04-24T00:00:00Z
date_updated: 2025-11-03T23:30:47Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: CaGu
doi: 10.15479/AT:ISTA:7680
file:
- access_level: open_access
  checksum: fb9a4468eb27be92690728e35c823796
  content_type: application/pdf
  creator: stgingl
  date_created: 2020-04-28T11:19:21Z
  date_updated: 2021-10-31T23:30:05Z
  embargo: 2021-10-30
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  file_name: Thesis_without-signatures_PDFA.pdf
  file_size: 3268017
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  checksum: f6c80ca97104a631a328cb79a2c53493
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  date_created: 2020-04-28T11:19:24Z
  date_updated: 2021-10-31T23:30:05Z
  embargo_to: open_access
  file_id: '7693'
  file_name: Thesis_without signatures.docx
  file_size: 5167703
  relation: source_file
file_date_updated: 2021-10-31T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: None
page: '98'
publication_identifier:
  eissn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '1028'
    relation: dissertation_contains
    status: public
status: public
supervisor:
- first_name: Harald L
  full_name: Janovjak, Harald L
  id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
  last_name: Janovjak
  orcid: 0000-0002-8023-9315
title: Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8434'
abstract:
- lang: eng
  text: 'Efficient migration on adhesive surfaces involves the protrusion of lamellipodial
    actin networks and their subsequent stabilization by nascent adhesions. The actin-binding
    protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium
    protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin
    filaments and by interacting with the WAVE regulatory complex, an activator of
    the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we
    demonstrate that genetic ablation of Lpd compromises protrusion efficiency and
    coincident cell migration without altering essential parameters of lamellipodia,
    including their maximal rate of forward advancement and actin polymerization.
    We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated
    Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover,
    computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia
    revealed that loss of Lpd correlates with reduced temporal protrusion maintenance
    as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes
    protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction
    and membrane ruffling.This article has an associated First Person interview with
    the first author of the paper. '
acknowledgement: This work was supported in part by Deutsche Forschungsgemeinschaft
  (DFG)[GRK2223/1, RO2414/5-1 (to K.R.), FA350/11-1 (to M.F.) and FA330/11-1 (to J.F.)],as
  well as by intramural funding from the Helmholtz Association (to T.E.B.S. andK.R.).
  G.D. was additionally funded by the Austrian Science Fund (FWF) LiseMeitner Program
  [M-2495]. A.C.H. and M.W. are supported by the Francis CrickInstitute, which receives
  its core funding from Cancer Research UK [FC001209], theMedical Research Council
  [FC001209] and the Wellcome Trust [FC001209]. M.K. issupported by the Biotechnology
  and Biological Sciences Research Council [BB/F011431/1, BB/J000590/1, BB/N000226/1].
  Deposited in PMC for release after 6months.
article_number: jcs239020
article_processing_charge: No
article_type: original
author:
- first_name: Georgi A
  full_name: Dimchev, Georgi A
  id: 38C393BE-F248-11E8-B48F-1D18A9856A87
  last_name: Dimchev
  orcid: 0000-0001-8370-6161
- first_name: Behnam
  full_name: Amiri, Behnam
  last_name: Amiri
- first_name: Ashley C.
  full_name: Humphries, Ashley C.
  last_name: Humphries
- first_name: Matthias
  full_name: Schaks, Matthias
  last_name: Schaks
- first_name: Vanessa
  full_name: Dimchev, Vanessa
  last_name: Dimchev
- first_name: Theresia E. B.
  full_name: Stradal, Theresia E. B.
  last_name: Stradal
- first_name: Jan
  full_name: Faix, Jan
  last_name: Faix
- first_name: Matthias
  full_name: Krause, Matthias
  last_name: Krause
- first_name: Michael
  full_name: Way, Michael
  last_name: Way
- first_name: Martin
  full_name: Falcke, Martin
  last_name: Falcke
- first_name: Klemens
  full_name: Rottner, Klemens
  last_name: Rottner
citation:
  ama: Dimchev GA, Amiri B, Humphries AC, et al. Lamellipodin tunes cell migration
    by stabilizing protrusions and promoting adhesion formation. <i>Journal of Cell
    Science</i>. 2020;133(7). doi:<a href="https://doi.org/10.1242/jcs.239020">10.1242/jcs.239020</a>
  apa: Dimchev, G. A., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal,
    T. E. B., … Rottner, K. (2020). Lamellipodin tunes cell migration by stabilizing
    protrusions and promoting adhesion formation. <i>Journal of Cell Science</i>.
    The Company of Biologists. <a href="https://doi.org/10.1242/jcs.239020">https://doi.org/10.1242/jcs.239020</a>
  chicago: Dimchev, Georgi A, Behnam Amiri, Ashley C. Humphries, Matthias Schaks,
    Vanessa Dimchev, Theresia E. B. Stradal, Jan Faix, et al. “Lamellipodin Tunes
    Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” <i>Journal
    of Cell Science</i>. The Company of Biologists, 2020. <a href="https://doi.org/10.1242/jcs.239020">https://doi.org/10.1242/jcs.239020</a>.
  ieee: G. A. Dimchev <i>et al.</i>, “Lamellipodin tunes cell migration by stabilizing
    protrusions and promoting adhesion formation,” <i>Journal of Cell Science</i>,
    vol. 133, no. 7. The Company of Biologists, 2020.
  ista: Dimchev GA, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix
    J, Krause M, Way M, Falcke M, Rottner K. 2020. Lamellipodin tunes cell migration
    by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science.
    133(7), jcs239020.
  mla: Dimchev, Georgi A., et al. “Lamellipodin Tunes Cell Migration by Stabilizing
    Protrusions and Promoting Adhesion Formation.” <i>Journal of Cell Science</i>,
    vol. 133, no. 7, jcs239020, The Company of Biologists, 2020, doi:<a href="https://doi.org/10.1242/jcs.239020">10.1242/jcs.239020</a>.
  short: G.A. Dimchev, B. Amiri, A.C. Humphries, M. Schaks, V. Dimchev, T.E.B. Stradal,
    J. Faix, M. Krause, M. Way, M. Falcke, K. Rottner, Journal of Cell Science 133
    (2020).
date_created: 2020-09-17T14:00:33Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2025-04-15T07:52:13Z
day: '09'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1242/jcs.239020
external_id:
  isi:
  - '000534387800005'
  pmid:
  - ' 32094266'
file:
- access_level: open_access
  checksum: ba917e551acc4ece2884b751434df9ae
  content_type: application/pdf
  creator: dernst
  date_created: 2020-09-17T14:07:51Z
  date_updated: 2020-10-11T22:30:02Z
  embargo: 2020-10-10
  file_id: '8435'
  file_name: 2020_JournalCellScience_Dimchev.pdf
  file_size: 13493302
  relation: main_file
file_date_updated: 2020-10-11T22:30:02Z
has_accepted_license: '1'
intvolume: '       133'
isi: 1
issue: '7'
keyword:
- Cell Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2674F658-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: M02495
  name: Protein structure and function in filopodia across scales
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lamellipodin tunes cell migration by stabilizing protrusions and promoting
  adhesion formation
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 133
year: '2020'
...
---
_id: '7889'
abstract:
- lang: eng
  text: Autoluminescent plants engineered to express a bacterial bioluminescence gene
    cluster in plastids have not been widely adopted because of low light output.
    We engineered tobacco plants with a fungal bioluminescence system that converts
    caffeic acid (present in all plants) into luciferin and report self-sustained
    luminescence that is visible to the naked eye. Our findings could underpin development
    of a suite of imaging tools for plants.
acknowledgement: "This study was designed, performed and funded by Planta LLC. We
  thank K. Wood for assisting in manuscript development. Planta acknowledges support
  from the Skolkovo Innovation Centre. We thank D. Bolotin and the Milaboratory (milaboratory.com)
  for access to computing and storage infrastructure. We thank S. Shakhov for providing\r\nphotography
  equipment. The Synthetic Biology Group is funded by the MRC London Institute of
  Medical Sciences (UKRI MC-A658-5QEA0, K.S.S.). K.S.S. is supported by an Imperial
  College Research Fellowship. Experiments were partially carried out using equipment
  provided by the Institute of Bioorganic Chemistry of the Russian Academy\r\nof Sciences
  Сore Facility (CKP IBCH; supported by the Russian Ministry of Education and Science
  Grant RFMEFI62117X0018). The F.A.K. lab is supported by ERC grant agreement 771209—CharFL.
  This project received funding from the European Union’s Horizon 2020 Research and
  Innovation Programme under Marie Skłodowska-Curie\r\nGrant Agreement 665385. K.S.S.
  acknowledges support by President’s Grant 075-15-2019-411. Design and assembly of
  some of the plasmids was supported by Russian Science Foundation grant 19-74-10102.
  Imaging experiments were partially supported by Russian Science Foundation grant
  17-14-01169p. LC-MS/MS analyses of extracts were\r\nsupported by Russian Science
  Foundation grant 16-14-00052p. Design and assembly of plasmids was partially supported
  by grant 075-15-2019-1789 from the Ministry of Science and Higher Education of the
  Russian Federation allocated to the Center for Precision Genome Editing and Genetic
  Technologies for Biomedicine. The authors\r\nwould like to acknowledge the work
  of Genomics Core Facility of the Skolkovo Institute of Science and Technology, which
  performed the sequencing and bioinformatic analysis."
article_processing_charge: No
article_type: original
author:
- first_name: Tatiana
  full_name: Mitiouchkina, Tatiana
  last_name: Mitiouchkina
- first_name: Alexander S.
  full_name: Mishin, Alexander S.
  last_name: Mishin
- first_name: Louisa
  full_name: Gonzalez Somermeyer, Louisa
  id: 4720D23C-F248-11E8-B48F-1D18A9856A87
  last_name: Gonzalez Somermeyer
  orcid: 0000-0001-9139-5383
- first_name: Nadezhda M.
  full_name: Markina, Nadezhda M.
  last_name: Markina
- first_name: Tatiana V.
  full_name: Chepurnyh, Tatiana V.
  last_name: Chepurnyh
- first_name: Elena B.
  full_name: Guglya, Elena B.
  last_name: Guglya
- first_name: Tatiana A.
  full_name: Karataeva, Tatiana A.
  last_name: Karataeva
- first_name: Kseniia A.
  full_name: Palkina, Kseniia A.
  last_name: Palkina
- first_name: Ekaterina S.
  full_name: Shakhova, Ekaterina S.
  last_name: Shakhova
- first_name: Liliia I.
  full_name: Fakhranurova, Liliia I.
  last_name: Fakhranurova
- first_name: Sofia V.
  full_name: Chekova, Sofia V.
  last_name: Chekova
- first_name: Aleksandra S.
  full_name: Tsarkova, Aleksandra S.
  last_name: Tsarkova
- first_name: Yaroslav V.
  full_name: Golubev, Yaroslav V.
  last_name: Golubev
- first_name: Vadim V.
  full_name: Negrebetsky, Vadim V.
  last_name: Negrebetsky
- first_name: Sergey A.
  full_name: Dolgushin, Sergey A.
  last_name: Dolgushin
- first_name: Pavel V.
  full_name: Shalaev, Pavel V.
  last_name: Shalaev
- first_name: Dmitry
  full_name: Shlykov, Dmitry
  last_name: Shlykov
- first_name: Olesya A.
  full_name: Melnik, Olesya A.
  last_name: Melnik
- first_name: Victoria O.
  full_name: Shipunova, Victoria O.
  last_name: Shipunova
- first_name: Sergey M.
  full_name: Deyev, Sergey M.
  last_name: Deyev
- first_name: Andrey I.
  full_name: Bubyrev, Andrey I.
  last_name: Bubyrev
- first_name: Alexander S.
  full_name: Pushin, Alexander S.
  last_name: Pushin
- first_name: Vladimir V.
  full_name: Choob, Vladimir V.
  last_name: Choob
- first_name: Sergey V.
  full_name: Dolgov, Sergey V.
  last_name: Dolgov
- first_name: Fyodor
  full_name: Kondrashov, Fyodor
  id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
  last_name: Kondrashov
  orcid: 0000-0001-8243-4694
- first_name: Ilia V.
  full_name: Yampolsky, Ilia V.
  last_name: Yampolsky
- first_name: Karen S.
  full_name: Sarkisyan, Karen S.
  last_name: Sarkisyan
citation:
  ama: Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, et al. Plants with genetically
    encoded autoluminescence. <i>Nature Biotechnology</i>. 2020;38:944-946. doi:<a
    href="https://doi.org/10.1038/s41587-020-0500-9">10.1038/s41587-020-0500-9</a>
  apa: Mitiouchkina, T., Mishin, A. S., Gonzalez Somermeyer, L., Markina, N. M., Chepurnyh,
    T. V., Guglya, E. B., … Sarkisyan, K. S. (2020). Plants with genetically encoded
    autoluminescence. <i>Nature Biotechnology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41587-020-0500-9">https://doi.org/10.1038/s41587-020-0500-9</a>
  chicago: Mitiouchkina, Tatiana, Alexander S. Mishin, Louisa Gonzalez Somermeyer,
    Nadezhda M. Markina, Tatiana V. Chepurnyh, Elena B. Guglya, Tatiana A. Karataeva,
    et al. “Plants with Genetically Encoded Autoluminescence.” <i>Nature Biotechnology</i>.
    Springer Nature, 2020. <a href="https://doi.org/10.1038/s41587-020-0500-9">https://doi.org/10.1038/s41587-020-0500-9</a>.
  ieee: T. Mitiouchkina <i>et al.</i>, “Plants with genetically encoded autoluminescence,”
    <i>Nature Biotechnology</i>, vol. 38. Springer Nature, pp. 944–946, 2020.
  ista: Mitiouchkina T, Mishin AS, Gonzalez Somermeyer L, Markina NM, Chepurnyh TV,
    Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV,
    Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Shlykov D,
    Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV,
    Kondrashov F, Yampolsky IV, Sarkisyan KS. 2020. Plants with genetically encoded
    autoluminescence. Nature Biotechnology. 38, 944–946.
  mla: Mitiouchkina, Tatiana, et al. “Plants with Genetically Encoded Autoluminescence.”
    <i>Nature Biotechnology</i>, vol. 38, Springer Nature, 2020, pp. 944–46, doi:<a
    href="https://doi.org/10.1038/s41587-020-0500-9">10.1038/s41587-020-0500-9</a>.
  short: T. Mitiouchkina, A.S. Mishin, L. Gonzalez Somermeyer, N.M. Markina, T.V.
    Chepurnyh, E.B. Guglya, T.A. Karataeva, K.A. Palkina, E.S. Shakhova, L.I. Fakhranurova,
    S.V. Chekova, A.S. Tsarkova, Y.V. Golubev, V.V. Negrebetsky, S.A. Dolgushin, P.V.
    Shalaev, D. Shlykov, O.A. Melnik, V.O. Shipunova, S.M. Deyev, A.I. Bubyrev, A.S.
    Pushin, V.V. Choob, S.V. Dolgov, F. Kondrashov, I.V. Yampolsky, K.S. Sarkisyan,
    Nature Biotechnology 38 (2020) 944–946.
date_created: 2020-05-25T15:02:00Z
date_published: 2020-04-27T00:00:00Z
date_updated: 2025-04-14T07:49:47Z
day: '27'
ddc:
- '570'
department:
- _id: FyKo
doi: 10.1038/s41587-020-0500-9
ec_funded: 1
external_id:
  isi:
  - '000529298800003'
  pmid:
  - '32341562'
file:
- access_level: open_access
  checksum: 1b30467500ec6277229a875b06e196d0
  content_type: application/pdf
  creator: dernst
  date_created: 2020-08-28T08:57:07Z
  date_updated: 2021-03-02T23:30:03Z
  embargo: 2021-03-01
  file_id: '8316'
  file_name: 2020_NatureBiotech_Mitiouchkina.pdf
  file_size: 1180086
  relation: main_file
file_date_updated: 2021-03-02T23:30:03Z
has_accepted_license: '1'
intvolume: '        38'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Submitted Version
page: 944-946
pmid: 1
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '771209'
  name: Characterizing the fitness landscape on population and global scales
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41587-020-0578-0
scopus_import: '1'
status: public
title: Plants with genetically encoded autoluminescence
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 38
year: '2020'
...
---
_id: '7426'
abstract:
- lang: eng
  text: This paper presents a novel abstraction technique for analyzing Lyapunov and
    asymptotic stability of polyhedral switched systems. A polyhedral switched system
    is a hybrid system in which the continuous dynamics is specified by polyhedral
    differential inclusions, the invariants and guards are specified by polyhedral
    sets and the switching between the modes do not involve reset of variables. A
    finite state weighted graph abstracting the polyhedral switched system is constructed
    from a finite partition of the state–space, such that the satisfaction of certain
    graph conditions, such as the absence of cycles with product of weights on the
    edges greater than (or equal) to 1, implies the stability of the system. However,
    the graph is in general conservative and hence, the violation of the graph conditions
    does not imply instability. If the analysis fails to establish stability due to
    the conservativeness in the approximation, a counterexample (cycle with product
    of edge weights greater than or equal to 1) indicating a potential reason for
    the failure is returned. Further, a more precise approximation of the switched
    system can be constructed by considering a finer partition of the state–space
    in the construction of the finite weighted graph. We present experimental results
    on analyzing stability of switched systems using the above method.
article_number: '100856'
article_processing_charge: No
article_type: original
author:
- first_name: Miriam
  full_name: Garcia Soto, Miriam
  id: 4B3207F6-F248-11E8-B48F-1D18A9856A87
  last_name: Garcia Soto
  orcid: 0000−0003−2936−5719
- first_name: Pavithra
  full_name: Prabhakar, Pavithra
  last_name: Prabhakar
citation:
  ama: 'Garcia Soto M, Prabhakar P. Abstraction based verification of stability of
    polyhedral switched systems. <i>Nonlinear Analysis: Hybrid Systems</i>. 2020;36(5).
    doi:<a href="https://doi.org/10.1016/j.nahs.2020.100856">10.1016/j.nahs.2020.100856</a>'
  apa: 'Garcia Soto, M., &#38; Prabhakar, P. (2020). Abstraction based verification
    of stability of polyhedral switched systems. <i>Nonlinear Analysis: Hybrid Systems</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.nahs.2020.100856">https://doi.org/10.1016/j.nahs.2020.100856</a>'
  chicago: 'Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification
    of Stability of Polyhedral Switched Systems.” <i>Nonlinear Analysis: Hybrid Systems</i>.
    Elsevier, 2020. <a href="https://doi.org/10.1016/j.nahs.2020.100856">https://doi.org/10.1016/j.nahs.2020.100856</a>.'
  ieee: 'M. Garcia Soto and P. Prabhakar, “Abstraction based verification of stability
    of polyhedral switched systems,” <i>Nonlinear Analysis: Hybrid Systems</i>, vol.
    36, no. 5. Elsevier, 2020.'
  ista: 'Garcia Soto M, Prabhakar P. 2020. Abstraction based verification of stability
    of polyhedral switched systems. Nonlinear Analysis: Hybrid Systems. 36(5), 100856.'
  mla: 'Garcia Soto, Miriam, and Pavithra Prabhakar. “Abstraction Based Verification
    of Stability of Polyhedral Switched Systems.” <i>Nonlinear Analysis: Hybrid Systems</i>,
    vol. 36, no. 5, 100856, Elsevier, 2020, doi:<a href="https://doi.org/10.1016/j.nahs.2020.100856">10.1016/j.nahs.2020.100856</a>.'
  short: 'M. Garcia Soto, P. Prabhakar, Nonlinear Analysis: Hybrid Systems 36 (2020).'
corr_author: '1'
date_created: 2020-02-02T23:00:59Z
date_published: 2020-05-01T00:00:00Z
date_updated: 2025-04-15T06:26:15Z
day: '01'
ddc:
- '000'
department:
- _id: ToHe
doi: 10.1016/j.nahs.2020.100856
external_id:
  isi:
  - '000528828600003'
file:
- access_level: open_access
  checksum: 560abfddb53f9fe921b6744f59f2cfaa
  content_type: application/pdf
  creator: dernst
  date_created: 2020-10-21T13:16:45Z
  date_updated: 2022-05-16T22:30:04Z
  embargo: 2022-05-15
  file_id: '8688'
  file_name: 2020_NAHS_GarciaSoto.pdf
  file_size: 818774
  relation: main_file
file_date_updated: 2022-05-16T22:30:04Z
has_accepted_license: '1'
intvolume: '        36'
isi: 1
issue: '5'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '05'
oa: 1
oa_version: Submitted Version
project:
- _id: 25863FF4-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: S11407
  name: Game Theory
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z211
  name: Formal methods for the design and analysis of complex systems
publication: 'Nonlinear Analysis: Hybrid Systems'
publication_identifier:
  issn:
  - 1751-570X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Abstraction based verification of stability of polyhedral switched systems
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 36
year: '2020'
...
---
_id: '7161'
abstract:
- lang: eng
  text: In this paper, we introduce an inertial projection-type method with different
    updating strategies for solving quasi-variational inequalities with strongly monotone
    and Lipschitz continuous operators in real Hilbert spaces. Under standard assumptions,
    we establish different strong convergence results for the proposed algorithm.
    Primary numerical experiments demonstrate the potential applicability of our scheme
    compared with some related methods in the literature.
acknowledgement: We are grateful to the anonymous referees and editor whose insightful
  comments helped to considerably improve an earlier version of this paper. The research
  of the first author is supported by an ERC Grant from the Institute of Science and
  Technology (IST).
article_processing_charge: No
article_type: original
author:
- first_name: Yekini
  full_name: Shehu, Yekini
  id: 3FC7CB58-F248-11E8-B48F-1D18A9856A87
  last_name: Shehu
  orcid: 0000-0001-9224-7139
- first_name: Aviv
  full_name: Gibali, Aviv
  last_name: Gibali
- first_name: Simone
  full_name: Sagratella, Simone
  last_name: Sagratella
citation:
  ama: Shehu Y, Gibali A, Sagratella S. Inertial projection-type methods for solving
    quasi-variational inequalities in real Hilbert spaces. <i>Journal of Optimization
    Theory and Applications</i>. 2020;184:877–894. doi:<a href="https://doi.org/10.1007/s10957-019-01616-6">10.1007/s10957-019-01616-6</a>
  apa: Shehu, Y., Gibali, A., &#38; Sagratella, S. (2020). Inertial projection-type
    methods for solving quasi-variational inequalities in real Hilbert spaces. <i>Journal
    of Optimization Theory and Applications</i>. Springer Nature. <a href="https://doi.org/10.1007/s10957-019-01616-6">https://doi.org/10.1007/s10957-019-01616-6</a>
  chicago: Shehu, Yekini, Aviv Gibali, and Simone Sagratella. “Inertial Projection-Type
    Methods for Solving Quasi-Variational Inequalities in Real Hilbert Spaces.” <i>Journal
    of Optimization Theory and Applications</i>. Springer Nature, 2020. <a href="https://doi.org/10.1007/s10957-019-01616-6">https://doi.org/10.1007/s10957-019-01616-6</a>.
  ieee: Y. Shehu, A. Gibali, and S. Sagratella, “Inertial projection-type methods
    for solving quasi-variational inequalities in real Hilbert spaces,” <i>Journal
    of Optimization Theory and Applications</i>, vol. 184. Springer Nature, pp. 877–894,
    2020.
  ista: Shehu Y, Gibali A, Sagratella S. 2020. Inertial projection-type methods for
    solving quasi-variational inequalities in real Hilbert spaces. Journal of Optimization
    Theory and Applications. 184, 877–894.
  mla: Shehu, Yekini, et al. “Inertial Projection-Type Methods for Solving Quasi-Variational
    Inequalities in Real Hilbert Spaces.” <i>Journal of Optimization Theory and Applications</i>,
    vol. 184, Springer Nature, 2020, pp. 877–894, doi:<a href="https://doi.org/10.1007/s10957-019-01616-6">10.1007/s10957-019-01616-6</a>.
  short: Y. Shehu, A. Gibali, S. Sagratella, Journal of Optimization Theory and Applications
    184 (2020) 877–894.
date_created: 2019-12-09T21:33:44Z
date_published: 2020-03-01T00:00:00Z
date_updated: 2024-11-04T13:52:44Z
day: '01'
ddc:
- '518'
- '510'
- '515'
department:
- _id: VlKo
doi: 10.1007/s10957-019-01616-6
ec_funded: 1
external_id:
  isi:
  - '000511805200009'
file:
- access_level: open_access
  checksum: 9f6dc6c6bf2b48cb3a2091a9ed5feaf2
  content_type: application/pdf
  creator: dernst
  date_created: 2020-10-12T10:40:27Z
  date_updated: 2021-03-16T23:30:04Z
  embargo: 2021-03-15
  file_id: '8647'
  file_name: 2020_JourOptimizationTheoryApplic_Shehu.pdf
  file_size: 332641
  relation: main_file
file_date_updated: 2021-03-16T23:30:04Z
has_accepted_license: '1'
intvolume: '       184'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Submitted Version
page: 877–894
project:
- _id: 25FBA906-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '616160'
  name: 'Discrete Optimization in Computer Vision: Theory and Practice'
publication: Journal of Optimization Theory and Applications
publication_identifier:
  eissn:
  - 1573-2878
  issn:
  - 0022-3239
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Inertial projection-type methods for solving quasi-variational inequalities
  in real Hilbert spaces
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 184
year: '2020'
...
---
_id: '8190'
article_number: e202007029
article_processing_charge: No
article_type: letter_note
author:
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Anna
  full_name: Huttenlocher, Anna
  last_name: Huttenlocher
citation:
  ama: 'Sixt MK, Huttenlocher A. Zena Werb (1945-2020): Cell biology in context. <i>The
    Journal of Cell Biology</i>. 2020;219(8). doi:<a href="https://doi.org/10.1083/jcb.202007029">10.1083/jcb.202007029</a>'
  apa: 'Sixt, M. K., &#38; Huttenlocher, A. (2020). Zena Werb (1945-2020): Cell biology
    in context. <i>The Journal of Cell Biology</i>. Rockefeller University Press.
    <a href="https://doi.org/10.1083/jcb.202007029">https://doi.org/10.1083/jcb.202007029</a>'
  chicago: 'Sixt, Michael K, and Anna Huttenlocher. “Zena Werb (1945-2020): Cell Biology
    in Context.” <i>The Journal of Cell Biology</i>. Rockefeller University Press,
    2020. <a href="https://doi.org/10.1083/jcb.202007029">https://doi.org/10.1083/jcb.202007029</a>.'
  ieee: 'M. K. Sixt and A. Huttenlocher, “Zena Werb (1945-2020): Cell biology in context,”
    <i>The Journal of Cell Biology</i>, vol. 219, no. 8. Rockefeller University Press,
    2020.'
  ista: 'Sixt MK, Huttenlocher A. 2020. Zena Werb (1945-2020): Cell biology in context.
    The Journal of Cell Biology. 219(8), e202007029.'
  mla: 'Sixt, Michael K., and Anna Huttenlocher. “Zena Werb (1945-2020): Cell Biology
    in Context.” <i>The Journal of Cell Biology</i>, vol. 219, no. 8, e202007029,
    Rockefeller University Press, 2020, doi:<a href="https://doi.org/10.1083/jcb.202007029">10.1083/jcb.202007029</a>.'
  short: M.K. Sixt, A. Huttenlocher, The Journal of Cell Biology 219 (2020).
date_created: 2020-08-02T22:00:57Z
date_published: 2020-07-22T00:00:00Z
date_updated: 2025-06-12T07:34:40Z
day: '22'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1083/jcb.202007029
external_id:
  isi:
  - '000573631000004'
  pmid:
  - '32699885'
file:
- access_level: open_access
  checksum: 30016d778d266b8e17d01094917873b8
  content_type: application/pdf
  creator: dernst
  date_created: 2020-08-04T13:11:52Z
  date_updated: 2021-02-02T23:30:03Z
  embargo: 2021-02-01
  file_id: '8200'
  file_name: 2020_JCB_Sixt.pdf
  file_size: 830725
  relation: main_file
file_date_updated: 2021-02-02T23:30:03Z
has_accepted_license: '1'
intvolume: '       219'
isi: 1
issue: '8'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: The Journal of Cell Biology
publication_identifier:
  eissn:
  - 1540-8140
publication_status: published
publisher: Rockefeller University Press
scopus_import: '1'
status: public
title: 'Zena Werb (1945-2020): Cell biology in context'
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 219
year: '2020'
...
---
_id: '8586'
abstract:
- lang: eng
  text: Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights
    into biological processes and structures within a native context. However, a major
    challenge still lies in the efficient and reproducible preparation of adherent
    cells for subsequent cryo-EM analysis. This is due to the sensitivity of many
    cellular specimens to the varying seeding and culturing conditions required for
    EM experiments, the often limited amount of cellular material and also the fragility
    of EM grids and their substrate. Here, we present low-cost and reusable 3D printed
    grid holders, designed to improve specimen preparation when culturing challenging
    cellular samples directly on grids. The described grid holders increase cell culture
    reproducibility and throughput, and reduce the resources required for cell culturing.
    We show that grid holders can be integrated into various cryo-EM workflows, including
    micro-patterning approaches to control cell seeding on grids, and for generating
    samples for cryo-focused ion beam milling and cryo-electron tomography experiments.
    Their adaptable design allows for the generation of specialized grid holders customized
    to a large variety of applications.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: This work was supported by the Austrian Science Fund (FWF, P33367)
  to FKMS. BZ acknowledges support by the Niederösterreich Fond. This research was
  also supported by the Scientific Service Units (SSU) of IST Austria through resources
  provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the
  BioImaging Facility (BIF) and the Electron Microscopy Facility (EMF). We thank Georgi
  Dimchev (IST Austria) and Sonja Jacob (Vienna Biocenter Core Facilities) for testing
  our grid holders in different experimental setups and Daniel Gütl and the Kondrashov
  group (IST Austria) for granting us repeated access to their 3D printers. We also
  thank Jonna Alanko and the Sixt lab (IST Austria) for providing us HeLa cells, primary
  BL6 mouse tail fibroblasts, NIH 3T3 fibroblasts and human telomerase immortalised
  foreskin fibroblasts for our experiments. We are thankful to Ori Avinoam and William
  Wan for helpful comments on the manuscript and also thank Dorotea Fracchiolla (Art&Science)
  for illustrating the graphical abstract.
article_number: '107633'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
  full_name: Fäßler, Florian
  id: 404F5528-F248-11E8-B48F-1D18A9856A87
  last_name: Fäßler
  orcid: 0000-0001-7149-769X
- first_name: Bettina
  full_name: Zens, Bettina
  id: 45FD126C-F248-11E8-B48F-1D18A9856A87
  last_name: Zens
  orcid: 0000-0002-9561-1239
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
citation:
  ama: Fäßler F, Zens B, Hauschild R, Schur FK. 3D printed cell culture grid holders
    for improved cellular specimen preparation in cryo-electron microscopy. <i>Journal
    of Structural Biology</i>. 2020;212(3). doi:<a href="https://doi.org/10.1016/j.jsb.2020.107633">10.1016/j.jsb.2020.107633</a>
  apa: Fäßler, F., Zens, B., Hauschild, R., &#38; Schur, F. K. (2020). 3D printed
    cell culture grid holders for improved cellular specimen preparation in cryo-electron
    microscopy. <i>Journal of Structural Biology</i>. Elsevier. <a href="https://doi.org/10.1016/j.jsb.2020.107633">https://doi.org/10.1016/j.jsb.2020.107633</a>
  chicago: Fäßler, Florian, Bettina Zens, Robert Hauschild, and Florian KM Schur.
    “3D Printed Cell Culture Grid Holders for Improved Cellular Specimen Preparation
    in Cryo-Electron Microscopy.” <i>Journal of Structural Biology</i>. Elsevier,
    2020. <a href="https://doi.org/10.1016/j.jsb.2020.107633">https://doi.org/10.1016/j.jsb.2020.107633</a>.
  ieee: F. Fäßler, B. Zens, R. Hauschild, and F. K. Schur, “3D printed cell culture
    grid holders for improved cellular specimen preparation in cryo-electron microscopy,”
    <i>Journal of Structural Biology</i>, vol. 212, no. 3. Elsevier, 2020.
  ista: Fäßler F, Zens B, Hauschild R, Schur FK. 2020. 3D printed cell culture grid
    holders for improved cellular specimen preparation in cryo-electron microscopy.
    Journal of Structural Biology. 212(3), 107633.
  mla: Fäßler, Florian, et al. “3D Printed Cell Culture Grid Holders for Improved
    Cellular Specimen Preparation in Cryo-Electron Microscopy.” <i>Journal of Structural
    Biology</i>, vol. 212, no. 3, 107633, Elsevier, 2020, doi:<a href="https://doi.org/10.1016/j.jsb.2020.107633">10.1016/j.jsb.2020.107633</a>.
  short: F. Fäßler, B. Zens, R. Hauschild, F.K. Schur, Journal of Structural Biology
    212 (2020).
corr_author: '1'
date_created: 2020-09-29T13:24:06Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2026-04-23T22:30:17Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1016/j.jsb.2020.107633
external_id:
  isi:
  - '000600997800008'
  pmid:
  - '32987119'
file:
- access_level: open_access
  checksum: c48cbf594e84fc2f91966ffaafc0918c
  content_type: application/pdf
  creator: dernst
  date_created: 2020-12-10T14:01:10Z
  date_updated: 2020-12-10T14:01:10Z
  file_id: '8937'
  file_name: 2020_JourStrucBiology_Faessler.pdf
  file_size: 7076870
  relation: main_file
  success: 1
file_date_updated: 2020-12-10T14:01:10Z
has_accepted_license: '1'
intvolume: '       212'
isi: 1
issue: '3'
keyword:
- electron microscopy
- cryo-EM
- EM sample preparation
- 3D printing
- cell culture
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
  grant_number: P33367
  name: Structure and isoform diversity of the Arp2/3 complex
- _id: 059B463C-7A3F-11EA-A408-12923DDC885E
  name: NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria
publication: Journal of Structural Biology
publication_identifier:
  issn:
  - 1047-8477
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '14592'
    relation: used_in_publication
    status: public
  - id: '12491'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: 3D printed cell culture grid holders for improved cellular specimen preparation
  in cryo-electron microscopy
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: 212
year: '2020'
...
---
_id: '9633'
abstract:
- lang: eng
  text: The search for biologically faithful synaptic plasticity rules has resulted
    in a large body of models. They are usually inspired by – and fitted to – experimental
    data, but they rarely produce neural dynamics that serve complex functions. These
    failures suggest that current plasticity models are still under-constrained by
    existing data. Here, we present an alternative approach that uses meta-learning
    to discover plausible synaptic plasticity rules. Instead of experimental data,
    the rules are constrained by the functions they implement and the structure they
    are meant to produce. Briefly, we parameterize synaptic plasticity rules by a
    Volterra expansion and then use supervised learning methods (gradient descent
    or evolutionary strategies) to minimize a problem-dependent loss function that
    quantifies how effectively a candidate plasticity rule transforms an initially
    random network into one with the desired function. We first validate our approach
    by re-discovering previously described plasticity rules, starting at the single-neuron
    level and “Oja’s rule”, a simple Hebbian plasticity rule that captures the direction
    of most variability of inputs to a neuron (i.e., the first principal component).
    We expand the problem to the network level and ask the framework to find Oja’s
    rule together with an anti-Hebbian rule such that an initially random two-layer
    firing-rate network will recover several principal components of the input space
    after learning. Next, we move to networks of integrate-and-fire neurons with plastic
    inhibitory afferents. We train for rules that achieve a target firing rate by
    countering tuned excitation. Our algorithm discovers a specific subset of the
    manifold of rules that can solve this task. Our work is a proof of principle of
    an automated and unbiased approach to unveil synaptic plasticity rules that obey
    biological constraints and can solve complex functions.
acknowledgement: We would like to thank Chaitanya Chintaluri, Georgia Christodoulou,
  Bill Podlaski and Merima Šabanovic for useful discussions and comments. This work
  was supported by a Wellcome Trust ´ Senior Research Fellowship (214316/Z/18/Z),
  a BBSRC grant (BB/N019512/1), an ERC consolidator Grant (SYNAPSEEK), a Leverhulme
  Trust Project Grant (RPG-2016-446), and funding from École Polytechnique, Paris.
article_processing_charge: No
author:
- first_name: Basile J
  full_name: Confavreux, Basile J
  id: C7610134-B532-11EA-BD9F-F5753DDC885E
  last_name: Confavreux
- first_name: Friedemann
  full_name: Zenke, Friedemann
  last_name: Zenke
- first_name: Everton J.
  full_name: Agnes, Everton J.
  last_name: Agnes
- first_name: Timothy
  full_name: Lillicrap, Timothy
  last_name: Lillicrap
- first_name: Tim P
  full_name: Vogels, Tim P
  id: CB6FF8D2-008F-11EA-8E08-2637E6697425
  last_name: Vogels
  orcid: 0000-0003-3295-6181
citation:
  ama: 'Confavreux BJ, Zenke F, Agnes EJ, Lillicrap T, Vogels TP. A meta-learning
    approach to (re)discover plasticity rules that carve a desired function into a
    neural network. In: <i>Advances in Neural Information Processing Systems</i>.
    Vol 33. ; 2020:16398-16408.'
  apa: Confavreux, B. J., Zenke, F., Agnes, E. J., Lillicrap, T., &#38; Vogels, T.
    P. (2020). A meta-learning approach to (re)discover plasticity rules that carve
    a desired function into a neural network. In <i>Advances in Neural Information
    Processing Systems</i> (Vol. 33, pp. 16398–16408). Vancouver, Canada.
  chicago: Confavreux, Basile J, Friedemann Zenke, Everton J. Agnes, Timothy Lillicrap,
    and Tim P Vogels. “A Meta-Learning Approach to (Re)Discover Plasticity Rules That
    Carve a Desired Function into a Neural Network.” In <i>Advances in Neural Information
    Processing Systems</i>, 33:16398–408, 2020.
  ieee: B. J. Confavreux, F. Zenke, E. J. Agnes, T. Lillicrap, and T. P. Vogels, “A
    meta-learning approach to (re)discover plasticity rules that carve a desired function
    into a neural network,” in <i>Advances in Neural Information Processing Systems</i>,
    Vancouver, Canada, 2020, vol. 33, pp. 16398–16408.
  ista: 'Confavreux BJ, Zenke F, Agnes EJ, Lillicrap T, Vogels TP. 2020. A meta-learning
    approach to (re)discover plasticity rules that carve a desired function into a
    neural network. Advances in Neural Information Processing Systems. NeurIPS: Conference
    on Neural Information Processing Systems vol. 33, 16398–16408.'
  mla: Confavreux, Basile J., et al. “A Meta-Learning Approach to (Re)Discover Plasticity
    Rules That Carve a Desired Function into a Neural Network.” <i>Advances in Neural
    Information Processing Systems</i>, vol. 33, 2020, pp. 16398–408.
  short: B.J. Confavreux, F. Zenke, E.J. Agnes, T. Lillicrap, T.P. Vogels, in:, Advances
    in Neural Information Processing Systems, 2020, pp. 16398–16408.
conference:
  end_date: 2020-12-12
  location: Vancouver, Canada
  name: 'NeurIPS: Conference on Neural Information Processing Systems'
  start_date: 2020-12-06
date_created: 2021-07-04T22:01:27Z
date_published: 2020-12-06T00:00:00Z
date_updated: 2026-04-23T22:30:20Z
day: '06'
department:
- _id: TiVo
ec_funded: 1
intvolume: '        33'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://proceedings.neurips.cc/paper/2020/hash/bdbd5ebfde4934142c8a88e7a3796cd5-Abstract.html
month: '12'
oa: 1
oa_version: Published Version
page: 16398-16408
project:
- _id: 0aacfa84-070f-11eb-9043-d7eb2c709234
  call_identifier: H2020
  grant_number: '819603'
  name: Learning the shape of synaptic plasticity rules for neuronal architectures
    and function through machine learning.
- _id: c084a126-5a5b-11eb-8a69-d75314a70a87
  grant_number: 214316/Z/18/Z
  name: What’s in a memory? Spatiotemporal dynamics in strongly coupled recurrent
    neuronal networks.
publication: Advances in Neural Information Processing Systems
publication_identifier:
  issn:
  - 1049-5258
publication_status: published
quality_controlled: '1'
related_material:
  link:
  - relation: is_continued_by
    url: https://doi.org/10.1101/2020.10.24.353409
  record:
  - id: '14422'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: A meta-learning approach to (re)discover plasticity rules that carve a desired
  function into a neural network
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 33
year: '2020'
...
---
OA_place: repository
OA_type: green
_id: '8707'
abstract:
- lang: eng
  text: Dynamic changes in the three-dimensional (3D) organization of chromatin are
    associated with central biological processes, such as transcription, replication
    and development. Therefore, the comprehensive identification and quantification
    of these changes is fundamental to understanding of evolutionary and regulatory
    mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity
    (CHESS), an algorithm for the comparison of chromatin contact maps and automatic
    differential feature extraction. We demonstrate the robustness of CHESS to experimental
    variability and showcase its biological applications on (1) interspecies comparisons
    of syntenic regions in human and mouse models; (2) intraspecies identification
    of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific
    aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and
    (4) the systematic identification of chromatin contact differences in high-resolution
    Capture-C data. In summary, CHESS is a computationally efficient method for the
    comparison and classification of changes in chromatin contact data.
acknowledgement: 'Work in the Vaquerizas laboratory is funded by the Max Planck Society,
  the Deutsche Forschungsgemeinschaft (DFG) Priority Programme SPP 2202 ‘Spatial Genome
  Architecture in Development and Disease’ (project no. 422857230 to J.M.V.), the
  DFG Clinical Research Unit CRU326 ‘Male Germ Cells: from Genes to Function’ (project
  no. 329621271 to J.M.V.), the European Union’s Horizon 2020 research and innovation
  programme under the Marie Skłodowska-Curie grant agreement no. 643062—ZENCODE-ITN
  to J.M.V.) and the Medical Research Council in the UK. This research was partially
  funded by the European Union’s H2020 Framework Programme through the European Research
  Council (grant no. 609989 to M.A.M.-R.). We thank the support of the Spanish Ministerio
  de Ciencia, Innovación y Universidades through grant no. BFU2017-85926-P to M.A.M.-R.
  The Centre for Genomic Regulation thanks the support of the Ministerio de Ciencia,
  Innovación y Universidades to the European Molecular Biology Laboratory partnership,
  the ‘Centro de Excelencia Severo Ochoa 2013–2017’, agreement no. SEV-2012-0208,
  the CERCA Programme/Generalitat de Catalunya, Spanish Ministerio de Ciencia, Innovación
  y Universidades through the Instituto de Salud Carlos III, the Generalitat de Catalunya
  through the Departament de Salut and Departament d’Empresa i Coneixement and cofinancing
  by the Spanish Ministerio de Ciencia, Innovación y Universidades with funds from
  the European Regional Development Fund corresponding to the 2014–2020 Smart Growth
  Operating Program. S.G. thanks the support from the Company of Biologists (grant
  no. JCSTF181158) and the European Molecular Biology Organization Short-Term Fellowship
  programme.'
article_processing_charge: No
article_type: original
author:
- first_name: Silvia
  full_name: ' Galan, Silvia'
  last_name: ' Galan'
- first_name: Nick N
  full_name: Machnik, Nick N
  id: 3591A0AA-F248-11E8-B48F-1D18A9856A87
  last_name: Machnik
  orcid: 0000-0001-6617-9742
- first_name: Kai
  full_name: Kruse, Kai
  last_name: Kruse
- first_name: Noelia
  full_name: Díaz, Noelia
  last_name: Díaz
- first_name: Marc A
  full_name: Marti-Renom, Marc A
  last_name: Marti-Renom
- first_name: Juan M
  full_name: Vaquerizas, Juan M
  last_name: Vaquerizas
citation:
  ama: Galan S, Machnik NN, Kruse K, Díaz N, Marti-Renom MA, Vaquerizas JM. CHESS
    enables quantitative comparison of chromatin contact data and automatic feature
    extraction. <i>Nature Genetics</i>. 2020;52:1247-1255. doi:<a href="https://doi.org/10.1038/s41588-020-00712-y">10.1038/s41588-020-00712-y</a>
  apa: Galan, S., Machnik, N. N., Kruse, K., Díaz, N., Marti-Renom, M. A., &#38; Vaquerizas,
    J. M. (2020). CHESS enables quantitative comparison of chromatin contact data
    and automatic feature extraction. <i>Nature Genetics</i>. Springer Nature. <a
    href="https://doi.org/10.1038/s41588-020-00712-y">https://doi.org/10.1038/s41588-020-00712-y</a>
  chicago: Galan, Silvia, Nick N Machnik, Kai Kruse, Noelia Díaz, Marc A Marti-Renom,
    and Juan M Vaquerizas. “CHESS Enables Quantitative Comparison of Chromatin Contact
    Data and Automatic Feature Extraction.” <i>Nature Genetics</i>. Springer Nature,
    2020. <a href="https://doi.org/10.1038/s41588-020-00712-y">https://doi.org/10.1038/s41588-020-00712-y</a>.
  ieee: S.  Galan, N. N. Machnik, K. Kruse, N. Díaz, M. A. Marti-Renom, and J. M.
    Vaquerizas, “CHESS enables quantitative comparison of chromatin contact data and
    automatic feature extraction,” <i>Nature Genetics</i>, vol. 52. Springer Nature,
    pp. 1247–1255, 2020.
  ista: Galan S, Machnik NN, Kruse K, Díaz N, Marti-Renom MA, Vaquerizas JM. 2020.
    CHESS enables quantitative comparison of chromatin contact data and automatic
    feature extraction. Nature Genetics. 52, 1247–1255.
  mla: Galan, Silvia, et al. “CHESS Enables Quantitative Comparison of Chromatin Contact
    Data and Automatic Feature Extraction.” <i>Nature Genetics</i>, vol. 52, Springer
    Nature, 2020, pp. 1247–55, doi:<a href="https://doi.org/10.1038/s41588-020-00712-y">10.1038/s41588-020-00712-y</a>.
  short: S.  Galan, N.N. Machnik, K. Kruse, N. Díaz, M.A. Marti-Renom, J.M. Vaquerizas,
    Nature Genetics 52 (2020) 1247–1255.
date_created: 2020-10-25T23:01:20Z
date_published: 2020-10-19T00:00:00Z
date_updated: 2026-04-23T22:30:25Z
day: '19'
department:
- _id: FyKo
doi: 10.1038/s41588-020-00712-y
external_id:
  isi:
  - '000579693500004'
  pmid:
  - '33077914'
intvolume: '        52'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://pmc.ncbi.nlm.nih.gov/articles/PMC7610641/
month: '10'
oa: 1
oa_version: Submitted Version
page: 1247-1255
pmid: 1
publication: Nature Genetics
publication_identifier:
  eissn:
  - 1546-1718
  issn:
  - 1061-4036
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '18642'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: CHESS enables quantitative comparison of chromatin contact data and automatic
  feature extraction
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 52
year: '2020'
...
---
_id: '7387'
abstract:
- lang: eng
  text: Most bacteria accomplish cell division with the help of a dynamic protein
    complex called the divisome, which spans the cell envelope in the plane of division.
    Assembly and activation of this machinery are coordinated by the tubulin-related
    GTPase FtsZ, which was found to form treadmilling filaments on supported bilayers
    in vitro1, as well as in live cells, in which filaments circle around the cell
    division site2,3. Treadmilling of FtsZ is thought to actively move proteins around
    the division septum, thereby distributing peptidoglycan synthesis and coordinating
    the inward growth of the septum to form the new poles of the daughter cells4.
    However, the molecular mechanisms underlying this function are largely unknown.
    Here, to study how FtsZ polymerization dynamics are coupled to downstream proteins,
    we reconstituted part of the bacterial cell division machinery using its purified
    components FtsZ, FtsA and truncated transmembrane proteins essential for cell
    division. We found that the membrane-bound cytosolic peptides of FtsN and FtsQ
    co-migrated with treadmilling FtsZ–FtsA filaments, but despite their directed
    collective behaviour, individual peptides showed random motion and transient confinement.
    Our work suggests that divisome proteins follow treadmilling FtsZ filaments by
    a diffusion-and-capture mechanism, which can give rise to a moving zone of signalling
    activity at the division site.
acknowledgement: We acknowledge members of the Loose laboratory at IST Austria for
  helpful discussions—in particular, P. Caldas for help with the treadmilling analysis,
  M. Jimenez, A. Raso and N. Ropero for providing Alexa Fluor 488- and Alexa Fluor
  647-labelled FtsA for the MST and analytical ultracentrifugation experiments. We
  thank C. You for providing the DODA-tris-NTA phospholipids, as well as J. Piehler
  and C. Richter (Department of Biology, University of Osnabruck, Germany) for the
  SLIMfast single-molecule tracking software and help with the confinement analysis.
  We thank J. Errington and H. Murray (both at Newcastle University, UK) for critical
  reading of the manuscript, and J. Brugués (MPI-CBG and MPI-PKS, Dresden, Germany)
  for help with the MATLAB programming and reading of the manuscript. This work was
  supported by the European Research Council through grant ERC-2015-StG-679239 to
  M.L. and grants HFSP LT 000824/2016-L4 and EMBO ALTF 1163-2015 to N.B., a grant
  from the Ministry of Economy and Competitiveness of the Spanish Government (BFU2016-75471-C2-1-P)
  to C.A. and G.R., and a Wellcome Trust Senior Investigator award (101824/Z/13/Z)
  and a grant from the BBSRC (BB/R017409/1) to W.V.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Natalia S.
  full_name: Baranova, Natalia S.
  id: 38661662-F248-11E8-B48F-1D18A9856A87
  last_name: Baranova
  orcid: 0000-0002-3086-9124
- first_name: Philipp
  full_name: Radler, Philipp
  id: 40136C2A-F248-11E8-B48F-1D18A9856A87
  last_name: Radler
  orcid: '0000-0001-9198-2182 '
- first_name: Víctor M.
  full_name: Hernández-Rocamora, Víctor M.
  last_name: Hernández-Rocamora
- first_name: Carlos
  full_name: Alfonso, Carlos
  last_name: Alfonso
- first_name: Maria D
  full_name: Lopez Pelegrin, Maria D
  id: 319AA9CE-F248-11E8-B48F-1D18A9856A87
  last_name: Lopez Pelegrin
- first_name: Germán
  full_name: Rivas, Germán
  last_name: Rivas
- first_name: Waldemar
  full_name: Vollmer, Waldemar
  last_name: Vollmer
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
citation:
  ama: Baranova NS, Radler P, Hernández-Rocamora VM, et al. Diffusion and capture
    permits dynamic coupling between treadmilling FtsZ filaments and cell division
    proteins. <i>Nature Microbiology</i>. 2020;5:407-417. doi:<a href="https://doi.org/10.1038/s41564-019-0657-5">10.1038/s41564-019-0657-5</a>
  apa: Baranova, N. S., Radler, P., Hernández-Rocamora, V. M., Alfonso, C., Lopez
    Pelegrin, M. D., Rivas, G., … Loose, M. (2020). Diffusion and capture permits
    dynamic coupling between treadmilling FtsZ filaments and cell division proteins.
    <i>Nature Microbiology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41564-019-0657-5">https://doi.org/10.1038/s41564-019-0657-5</a>
  chicago: Baranova, Natalia S., Philipp Radler, Víctor M. Hernández-Rocamora, Carlos
    Alfonso, Maria D Lopez Pelegrin, Germán Rivas, Waldemar Vollmer, and Martin Loose.
    “Diffusion and Capture Permits Dynamic Coupling between Treadmilling FtsZ Filaments
    and Cell Division Proteins.” <i>Nature Microbiology</i>. Springer Nature, 2020.
    <a href="https://doi.org/10.1038/s41564-019-0657-5">https://doi.org/10.1038/s41564-019-0657-5</a>.
  ieee: N. S. Baranova <i>et al.</i>, “Diffusion and capture permits dynamic coupling
    between treadmilling FtsZ filaments and cell division proteins,” <i>Nature Microbiology</i>,
    vol. 5. Springer Nature, pp. 407–417, 2020.
  ista: Baranova NS, Radler P, Hernández-Rocamora VM, Alfonso C, Lopez Pelegrin MD,
    Rivas G, Vollmer W, Loose M. 2020. Diffusion and capture permits dynamic coupling
    between treadmilling FtsZ filaments and cell division proteins. Nature Microbiology.
    5, 407–417.
  mla: Baranova, Natalia S., et al. “Diffusion and Capture Permits Dynamic Coupling
    between Treadmilling FtsZ Filaments and Cell Division Proteins.” <i>Nature Microbiology</i>,
    vol. 5, Springer Nature, 2020, pp. 407–17, doi:<a href="https://doi.org/10.1038/s41564-019-0657-5">10.1038/s41564-019-0657-5</a>.
  short: N.S. Baranova, P. Radler, V.M. Hernández-Rocamora, C. Alfonso, M.D. Lopez
    Pelegrin, G. Rivas, W. Vollmer, M. Loose, Nature Microbiology 5 (2020) 407–417.
corr_author: '1'
date_created: 2020-01-28T16:14:41Z
date_published: 2020-01-20T00:00:00Z
date_updated: 2026-04-23T22:30:25Z
day: '20'
department:
- _id: MaLo
doi: 10.1038/s41564-019-0657-5
ec_funded: 1
external_id:
  isi:
  - '000508584700007'
  pmid:
  - '31959972'
intvolume: '         5'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: http://europepmc.org/article/PMC/7048620
month: '01'
oa: 1
oa_version: Submitted Version
page: 407-417
pmid: 1
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '679239'
  name: Self-Organization of the Bacterial Cell
- _id: 259B655A-B435-11E9-9278-68D0E5697425
  grant_number: LT000824/2016
  name: Reconstitution of bacterial cell wall synthesis
- _id: 2596EAB6-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 2015-1163
  name: Synthesis of bacterial cell wall
publication: Nature Microbiology
publication_identifier:
  issn:
  - 2058-5276
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/little-cell-big-cover-story/
  record:
  - id: '14280'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Diffusion and capture permits dynamic coupling between treadmilling FtsZ filaments
  and cell division proteins
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 5
year: '2020'
...
---
_id: '7473'
abstract:
- lang: eng
  text: How structural and functional properties of synapses relate to each other
    is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms
    of synaptic transmission, and electron microscopy (EM) has provided insight into
    morphological properties of synapses. Here we describe an enhanced method for
    functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure
    freezing. We demonstrate that the improved method can be applied to intact networks
    in acute brain slices and organotypic slice cultures from mice. As a proof of
    concept, we probed vesicle pool changes during synaptic transmission at the hippocampal
    mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked
    vesicle pool and the functionally defined readily releasable pool and provide
    evidence of fast endocytosis at this synapse. Functional EM with acute slices
    and slice cultures has the potential to reveal the structural and functional mechanisms
    of transmission in intact, genetically perturbed, and disease-affected synapses.
acknowledgement: This project has received funding from the European Research Council
  (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research
  and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie
  708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27
  Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto
  for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa
  Zheden for extensive EM training, advice, and experimental assistance; Benjamin
  Suter for substantial help with light stimulation, ImageJ plugins for analysis,
  and manuscript editing; Florian Marr and Christina Altmutter for technical support;
  Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger
  (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing
  the Prox1-CreERT2 mouse line.
article_processing_charge: No
article_type: original
author:
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
  orcid: 0000-0003-2344-1039
- 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: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and
    Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>.
    2020;105:992-1006. doi:<a href="https://doi.org/10.1016/j.neuron.2019.12.022">10.1016/j.neuron.2019.12.022</a>
  apa: Borges Merjane, C., Kim, O., &#38; Jonas, P. M. (2020). Functional electron
    microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain
    slices. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2019.12.022">https://doi.org/10.1016/j.neuron.2019.12.022</a>
  chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron
    Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain
    Slices.” <i>Neuron</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.neuron.2019.12.022">https://doi.org/10.1016/j.neuron.2019.12.022</a>.
  ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy
    (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” <i>Neuron</i>,
    vol. 105. Elsevier, pp. 992–1006, 2020.
  ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash
    and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105,
    992–1006.
  mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and
    Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>,
    vol. 105, Elsevier, 2020, pp. 992–1006, doi:<a href="https://doi.org/10.1016/j.neuron.2019.12.022">10.1016/j.neuron.2019.12.022</a>.
  short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.
corr_author: '1'
date_created: 2020-02-10T15:59:45Z
date_published: 2020-03-18T00:00:00Z
date_updated: 2026-04-23T22:30:27Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2019.12.022
ec_funded: 1
external_id:
  isi:
  - '000520854700008'
  pmid:
  - '31928842'
file:
- access_level: open_access
  checksum: 3582664addf26859e86ac5bec3e01416
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-20T08:58:53Z
  date_updated: 2020-11-20T08:58:53Z
  file_id: '8778'
  file_name: 2020_Neuron_BorgesMerjane.pdf
  file_size: 9712957
  relation: main_file
  success: 1
file_date_updated: 2020-11-20T08:58:53Z
has_accepted_license: '1'
intvolume: '       105'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 992-1006
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '708497'
  name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
    mossy fiber synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01205
  name: Zellkommunikation in Gesundheit und Krankheit
publication: Neuron
publication_identifier:
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/
  record:
  - id: '11196'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Functional electron microscopy (“Flash and Freeze”) of identified cortical
  synapses in acute brain slices
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 105
year: '2020'
...
---
_id: '8139'
abstract:
- lang: eng
  text: 'Clathrin-mediated endocytosis (CME) is a crucial cellular process implicated
    in many aspects of plant growth, development, intra- and inter-cellular signaling,
    nutrient uptake and pathogen defense. Despite these significant roles, little
    is known about the precise molecular details of how it functions in planta. In
    order to facilitate the direct quantitative study of plant CME, here we review
    current routinely used methods and present refined, standardized quantitative
    imaging protocols which allow the detailed characterization of CME at multiple
    scales in plant tissues. These include: (i) an efficient electron microscopy protocol
    for the imaging of Arabidopsis CME vesicles in situ, thus providing a method for
    the detailed characterization of the ultra-structure of clathrin-coated vesicles;
    (ii) a detailed protocol and analysis for quantitative live-cell fluorescence
    microscopy to precisely examine the temporal interplay of endocytosis components
    during single CME events; (iii) a semi-automated analysis to allow the quantitative
    characterization of global internalization of cargos in whole plant tissues; and
    (iv) an overview and validation of useful genetic and pharmacological tools to
    interrogate the molecular mechanisms and function of CME in intact plant samples.'
acknowledged_ssus:
- _id: EM-Fac
- _id: Bio
acknowledgement: "This paper is dedicated to the memory of Christien Merrifield. He
  pioneered quantitative\r\nimaging approaches in mammalian CME and his mentorship
  inspired the development of all\r\nthe analysis methods presented here. His joy
  in research, pure scientific curiosity and\r\nmicroscopy excellence remain a constant
  inspiration. We thank Daniel Van Damme for gifting\r\nus the CLC2-GFP x TPLATE-TagRFP
  plants used in this manuscript. We further thank the\r\nScientific Service Units
  at IST Austria; specifically, the Electron Microscopy Facility for\r\ntechnical
  assistance (in particular Vanessa Zheden) and the BioImaging Facility BioImaging\r\nFacility
  for access to equipment. "
article_number: jcs248062
article_processing_charge: No
article_type: original
author:
- 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: Nataliia
  full_name: Gnyliukh, Nataliia
  id: 390C1120-F248-11E8-B48F-1D18A9856A87
  last_name: Gnyliukh
  orcid: 0000-0002-2198-0509
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Madhumitha
  full_name: Narasimhan, Madhumitha
  id: 44BF24D0-F248-11E8-B48F-1D18A9856A87
  last_name: Narasimhan
  orcid: 0000-0002-8600-0671
- first_name: G
  full_name: Vert, G
  last_name: Vert
- first_name: SY
  full_name: Bednarek, SY
  last_name: Bednarek
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Johnson AJ, Gnyliukh N, Kaufmann W, et al. Experimental toolbox for quantitative
    evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis. <i>Journal
    of Cell Science</i>. 2020;133(15). doi:<a href="https://doi.org/10.1242/jcs.248062">10.1242/jcs.248062</a>
  apa: Johnson, A. J., Gnyliukh, N., Kaufmann, W., Narasimhan, M., Vert, G., Bednarek,
    S., &#38; Friml, J. (2020). Experimental toolbox for quantitative evaluation of
    clathrin-mediated endocytosis in the plant model Arabidopsis. <i>Journal of Cell
    Science</i>. The Company of Biologists. <a href="https://doi.org/10.1242/jcs.248062">https://doi.org/10.1242/jcs.248062</a>
  chicago: Johnson, Alexander J, Nataliia Gnyliukh, Walter Kaufmann, Madhumitha Narasimhan,
    G Vert, SY Bednarek, and Jiří Friml. “Experimental Toolbox for Quantitative Evaluation
    of Clathrin-Mediated Endocytosis in the Plant Model Arabidopsis.” <i>Journal of
    Cell Science</i>. The Company of Biologists, 2020. <a href="https://doi.org/10.1242/jcs.248062">https://doi.org/10.1242/jcs.248062</a>.
  ieee: A. J. Johnson <i>et al.</i>, “Experimental toolbox for quantitative evaluation
    of clathrin-mediated endocytosis in the plant model Arabidopsis,” <i>Journal of
    Cell Science</i>, vol. 133, no. 15. The Company of Biologists, 2020.
  ista: Johnson AJ, Gnyliukh N, Kaufmann W, Narasimhan M, Vert G, Bednarek S, Friml
    J. 2020. Experimental toolbox for quantitative evaluation of clathrin-mediated
    endocytosis in the plant model Arabidopsis. Journal of Cell Science. 133(15),
    jcs248062.
  mla: Johnson, Alexander J., et al. “Experimental Toolbox for Quantitative Evaluation
    of Clathrin-Mediated Endocytosis in the Plant Model Arabidopsis.” <i>Journal of
    Cell Science</i>, vol. 133, no. 15, jcs248062, The Company of Biologists, 2020,
    doi:<a href="https://doi.org/10.1242/jcs.248062">10.1242/jcs.248062</a>.
  short: A.J. Johnson, N. Gnyliukh, W. Kaufmann, M. Narasimhan, G. Vert, S. Bednarek,
    J. Friml, Journal of Cell Science 133 (2020).
date_created: 2020-07-21T08:58:19Z
date_published: 2020-08-06T00:00:00Z
date_updated: 2026-04-23T22:30:28Z
day: '06'
ddc:
- '575'
department:
- _id: JiFr
- _id: EM-Fac
doi: 10.1242/jcs.248062
ec_funded: 1
external_id:
  isi:
  - '000561047900021'
  pmid:
  - '32616560'
file:
- access_level: open_access
  checksum: 2d11f79a0b4e0a380fb002b933da331a
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  creator: ajohnson
  date_created: 2020-11-26T17:12:51Z
  date_updated: 2021-08-08T22:30:03Z
  embargo: 2021-08-07
  file_id: '8815'
  file_name: 2020 - Johnson - JSC - plant CME toolbox.pdf
  file_size: 15150403
  relation: main_file
file_date_updated: 2021-08-08T22:30:03Z
has_accepted_license: '1'
intvolume: '       133'
isi: 1
issue: '15'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26538374-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03630
  name: Molecular mechanisms of endocytic cargo recognition in plants
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
related_material:
  record:
  - id: '14510'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis
  in the plant model Arabidopsis
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 133
year: '2020'
...
---
OA_place: publisher
_id: '7525'
abstract:
- lang: eng
  text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure
    important for the modulation of emotional memory. It is involved in regulation
    of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and
    feeding behavior. MHb receives inputs from septal regions and projects exclusively
    to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project
    to different subnuclei of MHb: the bed nucleus of anterior commissure projects
    to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore,
    the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively.
    Importantly, these projections have unique features of prominent co-release of
    different neurotransmitters and requirement of a peculiar type of calcium channel
    for release. In general, synaptic neurotransmission requires an activity-dependent
    influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels.
    The calcium channel family most commonly involved in neurotransmitter release
    comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits,
    respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or
    Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of
    the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements.
    This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique
    mechanisms of glutamate release in this pathway. One potential example of such
    uniqueness is the facilitation of release by GABAB receptor (GBR) activation.
    Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting
    presynaptic calcium channels. MHb shows the highest expression levels of GBR in
    the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are
    associated with auxiliary subunits, called potassium channel tetramerization domain
    containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b
    is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression
    in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b
    may be involved in the unique mechanisms of neurotransmitter release mediated
    by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we
    first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways
    is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482.
    We next found that baclofen, a GBR agonist, has facilitatory effects on release
    from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on
    release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed
    exclusively in ventral MHb may have a role in the facilitatory effects of GBR
    activation. In a heterologous expression system using HEK cells, we found that
    KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold
    electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely
    in presynaptic active zone in IPN with KCTD12b being present only in rostral/central
    but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely
    in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements
    and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3,
    KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating
    that they may form complexes regulating vesicle release in rostral IPN. \r\nOn
    electrophysiological studies of wild type (WT) mice, we found that paired-pulse
    ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT
    and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release
    probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8
    KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO
    mice, the mean variance analysis revealed significantly lower release probability
    in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional
    regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation
    in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8
    and KCTD12b KO mice, and found the facilitation of release remained in both KO
    mice, indicating that the peculiar effects of the GBR activation in this pathway
    do not depend on the selective expression of these KCTD subunits in ventral MHb.
    However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen
    falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and
    KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained
    potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in
    its termination in the absence of KCTD12b. Consistent with these functional findings,
    replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or
    GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT
    mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the
    release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn
    summary, our study provided new insights into the physiological roles of presynaptic
    Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal
    circuit. Future studies will be required to identify the exact molecular mechanism
    underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals.
    It remains to be determined whether the prominent presence of presynaptic KCTDs
    at active zone could exert similar neuromodulatory functions in different pathways
    of the brain.\r\n"
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
citation:
  ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula
    to interpeduncular nucleus pathway. 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:7525">10.15479/AT:ISTA:7525</a>
  apa: Bhandari, P. (2020). <i>Localization and functional role of Cav2.3 in the medial
    habenula to interpeduncular nucleus pathway</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/AT:ISTA:7525">https://doi.org/10.15479/AT:ISTA:7525</a>
  chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial
    Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology
    Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:7525">https://doi.org/10.15479/AT:ISTA:7525</a>.
  ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula
    to interpeduncular nucleus pathway,” Institute of Science and Technology Austria,
    2020.
  ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial
    habenula to interpeduncular nucleus pathway. Institute of Science and Technology
    Austria.
  mla: Bhandari, Pradeep. <i>Localization and Functional Role of Cav2.3 in the Medial
    Habenula to Interpeduncular Nucleus Pathway</i>. Institute of Science and Technology
    Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:7525">10.15479/AT:ISTA:7525</a>.
  short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula
    to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria,
    2020.
corr_author: '1'
date_created: 2020-02-26T10:56:37Z
date_published: 2020-02-28T00:00:00Z
date_updated: 2026-04-08T07:27:27Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:7525
file:
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  date_created: 2020-02-28T08:37:53Z
  date_updated: 2021-03-01T23:30:04Z
  embargo: 2021-02-28
  file_id: '7538'
  file_name: Pradeep Bhandari Thesis.pdf
  file_size: 9646346
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  title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
    nucleus pathway
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  title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
    nucleus pathway
file_date_updated: 2021-03-01T23:30:04Z
has_accepted_license: '1'
keyword:
- Cav2.3
- medial habenula (MHb)
- interpeduncular nucleus (IPN)
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '79'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
  nucleus pathway
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
OA_place: publisher
OA_type: hybrid
_id: '8002'
abstract:
- lang: eng
  text: Wound healing in plant tissues, consisting of rigid cell wall-encapsulated
    cells, represents a considerable challenge and occurs through largely unknown
    mechanisms distinct from those in animals. Owing to their inability to migrate,
    plant cells rely on targeted cell division and expansion to regenerate wounds.
    Strict coordination of these wound-induced responses is essential to ensure efficient,
    spatially restricted wound healing. Single-cell tracking by live imaging allowed
    us to gain mechanistic insight into the wound perception and coordination of wound
    responses after laser-based wounding in Arabidopsis root. We revealed a crucial
    contribution of the collapse of damaged cells in wound perception and detected
    an auxin increase specific to cells immediately adjacent to the wound. This localized
    auxin increase balances wound-induced cell expansion and restorative division
    rates in a dose-dependent manner, leading to tumorous overproliferation when the
    canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure
    changes together also spatially define the activation of key components of regeneration,
    such as the transcription regulator ERF115. Our observations suggest that the
    wound signaling involves the sensing of collapse of damaged cells and a local
    auxin signaling activation to coordinate the downstream transcriptional responses
    in the immediate wound vicinity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
article_number: '202003346'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Lukas
  full_name: Hörmayer, Lukas
  id: 2EEE7A2A-F248-11E8-B48F-1D18A9856A87
  last_name: Hörmayer
  orcid: 0000-0001-8295-2926
- first_name: Juan C
  full_name: Montesinos López, Juan C
  id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
  last_name: Montesinos López
  orcid: 0000-0001-9179-6099
- first_name: Petra
  full_name: Marhavá, Petra
  id: 44E59624-F248-11E8-B48F-1D18A9856A87
  last_name: Marhavá
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Saiko
  full_name: Yoshida, Saiko
  id: 2E46069C-F248-11E8-B48F-1D18A9856A87
  last_name: Yoshida
  orcid: 0000-0001-6111-9353
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J.
    Wounding-induced changes in cellular pressure and localized auxin signalling spatially
    coordinate restorative divisions in roots. <i>Proceedings of the National Academy
    of Sciences of the United States of America</i>. 2020;117(26). doi:<a href="https://doi.org/10.1073/pnas.2003346117">10.1073/pnas.2003346117</a>
  apa: Hörmayer, L., Montesinos López, J. C., Marhavá, P., Benková, E., Yoshida, S.,
    &#38; Friml, J. (2020). Wounding-induced changes in cellular pressure and localized
    auxin signalling spatially coordinate restorative divisions in roots. <i>Proceedings
    of the National Academy of Sciences of the United States of America</i>. National
    Academy of Sciences. <a href="https://doi.org/10.1073/pnas.2003346117">https://doi.org/10.1073/pnas.2003346117</a>
  chicago: Hörmayer, Lukas, Juan C Montesinos López, Petra Marhavá, Eva Benková, Saiko
    Yoshida, and Jiří Friml. “Wounding-Induced Changes in Cellular Pressure and Localized
    Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.” <i>Proceedings
    of the National Academy of Sciences of the United States of America</i>. National
    Academy of Sciences, 2020. <a href="https://doi.org/10.1073/pnas.2003346117">https://doi.org/10.1073/pnas.2003346117</a>.
  ieee: L. Hörmayer, J. C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, and
    J. Friml, “Wounding-induced changes in cellular pressure and localized auxin signalling
    spatially coordinate restorative divisions in roots,” <i>Proceedings of the National
    Academy of Sciences of the United States of America</i>, vol. 117, no. 26. National
    Academy of Sciences, 2020.
  ista: Hörmayer L, Montesinos López JC, Marhavá P, Benková E, Yoshida S, Friml J.
    2020. Wounding-induced changes in cellular pressure and localized auxin signalling
    spatially coordinate restorative divisions in roots. Proceedings of the National
    Academy of Sciences of the United States of America. 117(26), 202003346.
  mla: Hörmayer, Lukas, et al. “Wounding-Induced Changes in Cellular Pressure and
    Localized Auxin Signalling Spatially Coordinate Restorative Divisions in Roots.”
    <i>Proceedings of the National Academy of Sciences of the United States of America</i>,
    vol. 117, no. 26, 202003346, National Academy of Sciences, 2020, doi:<a href="https://doi.org/10.1073/pnas.2003346117">10.1073/pnas.2003346117</a>.
  short: L. Hörmayer, J.C. Montesinos López, P. Marhavá, E. Benková, S. Yoshida, J.
    Friml, Proceedings of the National Academy of Sciences of the United States of
    America 117 (2020).
corr_author: '1'
date_created: 2020-06-22T13:33:52Z
date_published: 2020-06-30T00:00:00Z
date_updated: 2026-04-23T22:30:35Z
day: '30'
ddc:
- '580'
department:
- _id: JiFr
- _id: EvBe
doi: 10.1073/pnas.2003346117
ec_funded: 1
external_id:
  isi:
  - '000565729700033'
  pmid:
  - '32541049'
file:
- access_level: open_access
  checksum: 908b09437680181de9990915f2113aca
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  date_created: 2020-06-23T11:30:53Z
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  file_id: '8009'
  file_name: 2020_PNAS_Hoermayer.pdf
  file_size: 2407102
  relation: main_file
file_date_updated: 2020-07-14T12:48:07Z
has_accepted_license: '1'
intvolume: '       117'
isi: 1
issue: '26'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 262EF96E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29988
  name: RNA-directed DNA methylation in plant development
publication: Proceedings of the National Academy of Sciences of the United States
  of America
publication_identifier:
  eissn:
  - 1091-6490
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/how-wounded-plants-coordinate-their-healing/
  record:
  - id: '9992'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Wounding-induced changes in cellular pressure and localized auxin signalling
  spatially coordinate restorative divisions in roots
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: 117
year: '2020'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '9160'
abstract:
- lang: eng
  text: Auxin is a key hormonal regulator, that governs plant growth and development
    in concert with other hormonal pathways. The unique feature of auxin is its polar,
    cell-to-cell transport that leads to the formation of local auxin maxima and gradients,
    which coordinate initiation and patterning of plant organs. The molecular machinery
    mediating polar auxin transport is one of the important points of interaction
    with other hormones. Multiple hormonal pathways converge at the regulation of
    auxin transport and form a regulatory network that integrates various developmental
    and environmental inputs to steer plant development. In this review, we discuss
    recent advances in understanding the mechanisms that underlie regulation of polar
    auxin transport by multiple hormonal pathways. Specifically, we focus on the post-translational
    mechanisms that contribute to fine-tuning of the abundance and polarity of auxin
    transporters at the plasma membrane and thereby enable rapid modification of the
    auxin flow to coordinate plant growth and development.
acknowledgement: H.S. is the recipient of a DOC Fellowship of the Austrian Academy
  of Sciences at the Institute of Science and Technology, Austria. J.C.M. is the recipient
  of an EMBO Long-Term Fellowship (ALTF number 710-2016). We would like to thank Jiri
  Friml and Carina Baskett for critical reading of the manuscript and Shutang Tan
  and Maciek Adamowski for helpful discussions. No conflict of interest declared.
article_number: '100048'
article_processing_charge: No
article_type: original
author:
- first_name: Hana
  full_name: Semeradova, Hana
  id: 42FE702E-F248-11E8-B48F-1D18A9856A87
  last_name: Semeradova
- first_name: Juan C
  full_name: Montesinos López, Juan C
  id: 310A8E3E-F248-11E8-B48F-1D18A9856A87
  last_name: Montesinos López
  orcid: 0000-0001-9179-6099
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
citation:
  ama: 'Semerádová H, Montesinos López JC, Benková E. All roads lead to auxin: Post-translational
    regulation of auxin transport by multiple hormonal pathways. <i>Plant Communications</i>.
    2020;1(3). doi:<a href="https://doi.org/10.1016/j.xplc.2020.100048">10.1016/j.xplc.2020.100048</a>'
  apa: 'Semerádová, H., Montesinos López, J. C., &#38; Benková, E. (2020). All roads
    lead to auxin: Post-translational regulation of auxin transport by multiple hormonal
    pathways. <i>Plant Communications</i>. Elsevier. <a href="https://doi.org/10.1016/j.xplc.2020.100048">https://doi.org/10.1016/j.xplc.2020.100048</a>'
  chicago: 'Semerádová, Hana, Juan C Montesinos López, and Eva Benková. “All Roads
    Lead to Auxin: Post-Translational Regulation of Auxin Transport by Multiple Hormonal
    Pathways.” <i>Plant Communications</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.xplc.2020.100048">https://doi.org/10.1016/j.xplc.2020.100048</a>.'
  ieee: 'H. Semerádová, J. C. Montesinos López, and E. Benková, “All roads lead to
    auxin: Post-translational regulation of auxin transport by multiple hormonal pathways,”
    <i>Plant Communications</i>, vol. 1, no. 3. Elsevier, 2020.'
  ista: 'Semerádová H, Montesinos López JC, Benková E. 2020. All roads lead to auxin:
    Post-translational regulation of auxin transport by multiple hormonal pathways.
    Plant Communications. 1(3), 100048.'
  mla: 'Semerádová, Hana, et al. “All Roads Lead to Auxin: Post-Translational Regulation
    of Auxin Transport by Multiple Hormonal Pathways.” <i>Plant Communications</i>,
    vol. 1, no. 3, 100048, Elsevier, 2020, doi:<a href="https://doi.org/10.1016/j.xplc.2020.100048">10.1016/j.xplc.2020.100048</a>.'
  short: H. Semerádová, J.C. Montesinos López, E. Benková, Plant Communications 1
    (2020).
corr_author: '1'
date_created: 2021-02-18T10:18:43Z
date_published: 2020-05-11T00:00:00Z
date_updated: 2026-04-23T22:30:36Z
day: '11'
ddc:
- '580'
department:
- _id: EvBe
doi: 10.1016/j.xplc.2020.100048
external_id:
  isi:
  - '000654052800010'
  pmid:
  - '33367243'
file:
- access_level: open_access
  checksum: 785b266d82a94b007cf40dbbe7c4847e
  content_type: application/pdf
  creator: dernst
  date_created: 2021-02-18T10:23:59Z
  date_updated: 2021-02-18T10:23:59Z
  file_id: '9161'
  file_name: 2020_PlantComm_Semeradova.pdf
  file_size: 840289
  relation: main_file
  success: 1
file_date_updated: 2021-02-18T10:23:59Z
has_accepted_license: '1'
intvolume: '         1'
isi: 1
issue: '3'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261821BC-B435-11E9-9278-68D0E5697425
  grant_number: '24746'
  name: Molecular mechanisms of the cytokinin regulated endomembrane trafficking to
    coordinate plant organogenesis
- _id: 253E54C8-B435-11E9-9278-68D0E5697425
  grant_number: ALTF710-2016
  name: Molecular mechanism of auxindriven formative divisions delineating lateral
    root organogenesis in plants
publication: Plant Communications
publication_identifier:
  issn:
  - 2590-3462
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '10135'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: 'All roads lead to auxin: Post-translational regulation of auxin transport
  by multiple hormonal pathways'
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: 0043cee0-e5fc-11ee-9736-f83bc23afbf0
volume: 1
year: '2020'
...
---
_id: '8831'
abstract:
- lang: eng
  text: Holes in planar Ge have high mobilities, strong spin-orbit interaction and
    electrically tunable g-factors, and are therefore emerging as a promising candidate
    for hybrid superconductorsemiconductor devices. This is further motivated by the
    observation of supercurrent transport in planar Ge Josephson Field effect transistors
    (JoFETs). A key challenge towards hybrid germanium quantum technology is the design
    of high quality interfaces and superconducting contacts that are robust against
    magnetic fields. By combining the assets of Al, which has a long superconducting
    coherence, and Nb, which has a significant superconducting gap, we form low-disordered
    JoFETs with large ICRN products that are capable of withstanding high magnetic
    fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs
    opening up an avenue to explore topological superconductivity in planar Ge. The
    persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves
    the way towards integrating spin qubits and proximity-induced superconductivity
    on the same chip.
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
acknowledgement: "This research and related results were made possible with the support
  of the NOMIS Foundation. This research was supported by the Scientific Service Units
  of IST Austria through resources provided by the MIBA Machine Shop and the nanofabrication
  facility, the European Union’s Horizon 2020 research and innovation program under
  the Marie Sklodowska-Curie grant agreement #844511 and the Grant Agreement #862046.
  ICN2 acknowledge funding from Generalitat de Catalunya 2017 SGR 327. ICN2 is supported
  by the Severo Ochoa\r\nprogram from Spanish MINECO (Grant No. SEV2017-0706) and
  is funded by the CERCA Programme / Generalitat de Catalunya. Part of the present
  work has been performed in the framework of Universitat Aut`onoma de Barcelona Materials
  Science PhD program. The HAADF-STEM microscopy was conducted in the Laboratorio
  de Microscopias Avanzadas at Instituto de Nanociencia de Aragon-Universidad de Zaragoza.
  Authors acknowledge the LMA-INA for offering access to their instruments and expertise.
  We acknowledge support from CSIC Research Platform on Quantum Technologies PTI-001.
  This project has received funding from\r\nthe European Union’s Horizon 2020 research
  and innovation programme under grant agreement No 823717 – ESTEEM3. M.B. acknowledges
  support from SUR Generalitat de Catalunya and the EU Social Fund; project ref. 2020
  FI 00103. GS and MV acknowledge support through a projectruimte grant associated
  with the Netherlands Organization of Scientific Research (NWO)."
article_number: '2012.00322'
article_processing_charge: No
arxiv: 1
author:
- first_name: Kushagra
  full_name: Aggarwal, Kushagra
  id: b22ab905-3539-11eb-84c3-fc159dcd79cb
  last_name: Aggarwal
  orcid: 0000-0001-9985-9293
- first_name: Andrea C
  full_name: Hofmann, Andrea C
  id: 340F461A-F248-11E8-B48F-1D18A9856A87
  last_name: Hofmann
- first_name: Daniel
  full_name: Jirovec, Daniel
  id: 4C473F58-F248-11E8-B48F-1D18A9856A87
  last_name: Jirovec
  orcid: 0000-0002-7197-4801
- first_name: Ivan
  full_name: Prieto Gonzalez, Ivan
  id: 2A307FE2-F248-11E8-B48F-1D18A9856A87
  last_name: Prieto Gonzalez
  orcid: 0000-0002-7370-5357
- first_name: Amir
  full_name: Sammak, Amir
  last_name: Sammak
- first_name: Marc
  full_name: Botifoll, Marc
  last_name: Botifoll
- first_name: Sara
  full_name: Marti-Sanchez, Sara
  last_name: Marti-Sanchez
- first_name: Menno
  full_name: Veldhorst, Menno
  last_name: Veldhorst
- first_name: Jordi
  full_name: Arbiol, Jordi
  last_name: Arbiol
- first_name: Giordano
  full_name: Scappucci, Giordano
  last_name: Scappucci
- first_name: Georgios
  full_name: Katsaros, Georgios
  id: 38DB5788-F248-11E8-B48F-1D18A9856A87
  last_name: Katsaros
  orcid: 0000-0001-8342-202X
citation:
  ama: Aggarwal K, Hofmann AC, Jirovec D, et al. Enhancement of proximity induced
    superconductivity in planar Germanium. <i>arXiv</i>. doi:<a href="https://doi.org/10.48550/arXiv.2012.00322">10.48550/arXiv.2012.00322</a>
  apa: Aggarwal, K., Hofmann, A. C., Jirovec, D., Prieto Gonzalez, I., Sammak, A.,
    Botifoll, M., … Katsaros, G. (n.d.). Enhancement of proximity induced superconductivity
    in planar Germanium. <i>arXiv</i>. <a href="https://doi.org/10.48550/arXiv.2012.00322">https://doi.org/10.48550/arXiv.2012.00322</a>
  chicago: Aggarwal, Kushagra, Andrea C Hofmann, Daniel Jirovec, Ivan Prieto Gonzalez,
    Amir Sammak, Marc Botifoll, Sara Marti-Sanchez, et al. “Enhancement of Proximity
    Induced Superconductivity in Planar Germanium.” <i>ArXiv</i>, n.d. <a href="https://doi.org/10.48550/arXiv.2012.00322">https://doi.org/10.48550/arXiv.2012.00322</a>.
  ieee: K. Aggarwal <i>et al.</i>, “Enhancement of proximity induced superconductivity
    in planar Germanium,” <i>arXiv</i>. .
  ista: Aggarwal K, Hofmann AC, Jirovec D, Prieto Gonzalez I, Sammak A, Botifoll M,
    Marti-Sanchez S, Veldhorst M, Arbiol J, Scappucci G, Katsaros G. Enhancement of
    proximity induced superconductivity in planar Germanium. arXiv, 2012.00322.
  mla: Aggarwal, Kushagra, et al. “Enhancement of Proximity Induced Superconductivity
    in Planar Germanium.” <i>ArXiv</i>, 2012.00322, doi:<a href="https://doi.org/10.48550/arXiv.2012.00322">10.48550/arXiv.2012.00322</a>.
  short: K. Aggarwal, A.C. Hofmann, D. Jirovec, I. Prieto Gonzalez, A. Sammak, M.
    Botifoll, S. Marti-Sanchez, M. Veldhorst, J. Arbiol, G. Scappucci, G. Katsaros,
    ArXiv (n.d.).
corr_author: '1'
date_created: 2020-12-02T10:42:53Z
date_published: 2020-12-02T00:00:00Z
date_updated: 2026-04-23T22:30:36Z
day: '02'
ddc:
- '530'
department:
- _id: GeKa
doi: 10.48550/arXiv.2012.00322
ec_funded: 1
external_id:
  arxiv:
  - '2012.00322'
file:
- access_level: open_access
  checksum: 22a612e206232fa94b138b2c2f957582
  content_type: application/pdf
  creator: gkatsaro
  date_created: 2020-12-02T10:42:31Z
  date_updated: 2020-12-02T10:42:31Z
  file_id: '8832'
  file_name: Superconducting_2D_Ge.pdf
  file_size: 1697939
  relation: main_file
file_date_updated: 2020-12-02T10:42:31Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
project:
- _id: 262116AA-B435-11E9-9278-68D0E5697425
  name: Hybrid Semiconductor - Superconductor Quantum Devices
- _id: 26A151DA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '844511'
  name: Majorana bound states in Ge/SiGe heterostructures
- _id: 237E5020-32DE-11EA-91FC-C7463DDC885E
  call_identifier: H2020
  grant_number: '862046'
  name: TOPOLOGICALLY PROTECTED AND SCALABLE QUANTUM BITS
publication: arXiv
publication_status: draft
related_material:
  record:
  - id: '10559'
    relation: later_version
    status: public
  - id: '8834'
    relation: research_data
    status: public
  - id: '10058'
    relation: dissertation_contains
    status: public
status: public
title: Enhancement of proximity induced superconductivity in planar Germanium
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8532'
abstract:
- lang: eng
  text: The molecular anatomy of synapses defines their characteristics in transmission
    and plasticity. Precise measurements of the number and distribution of synaptic
    proteins are important for our understanding of synapse heterogeneity within and
    between brain regions. Freeze–fracture replica immunogold electron microscopy
    enables us to analyze them quantitatively on a two-dimensional membrane surface.
    Here, we introduce Darea software, which utilizes deep learning for analysis of
    replica images and demonstrate its usefulness for quick measurements of the pre-
    and postsynaptic areas, density and distribution of gold particles at synapses
    in a reproducible manner. We used Darea for comparing glutamate receptor and calcium
    channel distributions between hippocampal CA3-CA1 spine synapses on apical and
    basal dendrites, which differ in signaling pathways involved in synaptic plasticity.
    We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
    acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic
    size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA)
    receptors with size. Interestingly, AMPA and NMDA receptors are segregated within
    postsynaptic sites and negatively correlated in density among both apical and
    basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels
    show similar densities in apical and basal synapses with distributions consistent
    with an exclusion zone model of calcium channel-release site topography.
acknowledgement: "This research was funded by Austrian Academy of Sciences, DOC fellowship
  to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human
  Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner
  for technical support."
article_number: '6737'
article_processing_charge: No
article_type: original
author:
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Jacqueline-Claire
  full_name: Montanaro-Punzengruber, Jacqueline-Claire
  id: 3786AB44-F248-11E8-B48F-1D18A9856A87
  last_name: Montanaro-Punzengruber
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: Matthew J
  full_name: Case, Matthew J
  id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
  last_name: Case
- first_name: Yugo
  full_name: Fukazawa, Yugo
  last_name: Fukazawa
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
    Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture
    replica images applied to glutamate receptors and calcium channels at hippocampal
    synapses. <i>International Journal of Molecular Sciences</i>. 2020;21(18). doi:<a
    href="https://doi.org/10.3390/ijms21186737">10.3390/ijms21186737</a>
  apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J.,
    Fukazawa, Y., &#38; Shigemoto, R. (2020). Deep learning-assisted high-throughput
    analysis of freeze-fracture replica images applied to glutamate receptors and
    calcium channels at hippocampal synapses. <i>International Journal of Molecular
    Sciences</i>. MDPI. <a href="https://doi.org/10.3390/ijms21186737">https://doi.org/10.3390/ijms21186737</a>
  chicago: Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari,
    Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted
    High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate
    Receptors and Calcium Channels at Hippocampal Synapses.” <i>International Journal
    of Molecular Sciences</i>. MDPI, 2020. <a href="https://doi.org/10.3390/ijms21186737">https://doi.org/10.3390/ijms21186737</a>.
  ieee: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y.
    Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of
    freeze-fracture replica images applied to glutamate receptors and calcium channels
    at hippocampal synapses,” <i>International Journal of Molecular Sciences</i>,
    vol. 21, no. 18. MDPI, 2020.
  ista: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
    Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture
    replica images applied to glutamate receptors and calcium channels at hippocampal
    synapses. International Journal of Molecular Sciences. 21(18), 6737.
  mla: Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis
    of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels
    at Hippocampal Synapses.” <i>International Journal of Molecular Sciences</i>,
    vol. 21, no. 18, 6737, MDPI, 2020, doi:<a href="https://doi.org/10.3390/ijms21186737">10.3390/ijms21186737</a>.
  short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y.
    Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).
corr_author: '1'
date_created: 2020-09-20T22:01:35Z
date_published: 2020-09-14T00:00:00Z
date_updated: 2026-04-23T22:30:37Z
day: '14'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3390/ijms21186737
ec_funded: 1
external_id:
  isi:
  - '000579945300001'
file:
- access_level: open_access
  checksum: 2e4f62f3cfe945b7391fc3070e5a289f
  content_type: application/pdf
  creator: dernst
  date_created: 2020-09-21T14:08:58Z
  date_updated: 2020-09-21T14:08:58Z
  file_id: '8551'
  file_name: 2020_JournMolecSciences_Kleindienst.pdf
  file_size: 5748456
  relation: main_file
  success: 1
file_date_updated: 2020-09-21T14:08:58Z
has_accepted_license: '1'
intvolume: '        21'
isi: 1
issue: '18'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 25D32BC0-B435-11E9-9278-68D0E5697425
  name: Mechanism of formation and maintenance of input side-dependent asymmetry in
    the hippocampus
- _id: 26436750-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '785907'
  name: Human Brain Project Specific Grant Agreement 2
publication: International Journal of Molecular Sciences
publication_identifier:
  eissn:
  - 1422-0067
  issn:
  - 1661-6596
publication_status: published
publisher: MDPI
quality_controlled: '1'
related_material:
  record:
  - id: '9562'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Deep learning-assisted high-throughput analysis of freeze-fracture replica
  images applied to glutamate receptors and calcium channels at hippocampal synapses
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: 21
year: '2020'
...
---
OA_place: publisher
_id: '8657'
abstract:
- lang: eng
  text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
    studies anchor translation into the context of bacterial physiology and reveal
    several mathematical relationships, called “growth laws,” which capture physiological
    feedbacks between protein synthesis and cell growth. Growth laws describe the
    dependency of the ribosome abundance as a function of growth rate, which can change
    depending on the growth conditions. Perturbations of translation reveal that bacteria
    employ a compensatory strategy in which the reduced translation capability results
    in increased expression of the translation machinery.\r\nPerturbations of translation
    are achieved in various ways; clinically interesting is the application of translation-targeting
    antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
    are often poorly understood. Bacterial responses to two or more simultaneously
    applied antibiotics are even more puzzling. The combined antibiotic effect determines
    the type of drug interaction, which ranges from synergy (the effect is stronger
    than expected) to antagonism (the effect is weaker) and suppression (one of the
    drugs loses its potency).\r\nIn the first part of this work, we systematically
    measure the pairwise interaction network for translation inhibitors that interfere
    with different steps in translation. We find that the interactions are surprisingly
    diverse and tend to be more antagonistic. To explore the underlying mechanisms,
    we begin with a minimal biophysical model of combined antibiotic action. We base
    this model on the kinetics of antibiotic uptake and binding together with the
    physiological response described by the growth laws. The biophysical model explains
    some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
    the second part of this work, we hypothesize that elusive suppressive drug interactions
    result from the interplay between ribosomes halted in different stages of translation.
    To elucidate this putative mechanism of drug interactions between translation
    inhibitors, we generate translation bottlenecks genetically using in- ducible
    control of translation factors that regulate well-defined translation cycle steps.
    These perturbations accurately mimic antibiotic action and drug interactions,
    supporting that the interplay of different translation bottlenecks partially causes
    these interactions.\r\nWe extend this approach by varying two translation bottlenecks
    simultaneously. This approach reveals the suppression of translocation inhibition
    by inhibited translation. We rationalize this effect by modeling dense traffic
    of ribosomes that move on transcripts in a translation factor-mediated manner.
    This model predicts a dissolution of traffic jams caused by inhibited translocation
    when the density of ribosome traffic is reduced by lowered initiation. We base
    this model on the growth laws and quantitative relationships between different
    translation and growth parameters.\r\nIn the final part of this work, we describe
    a set of tools aimed at quantification of physiological and translation parameters.
    We further develop a simple model that directly connects the abundance of a translation
    factor with the growth rate, which allows us to extract physiological parameters
    describing initiation. We demonstrate the development of tools for measuring translation
    rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
    mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
    Furthermore, by a gradual transition from combinations of antibiotics to precise
    genetic interventions, we demonstrated the equivalency between genetic and chemi-
    cal perturbations of translation. These findings tile the path for quantitative
    studies of antibiotic combinations and illustrate future approaches towards the
    quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
  providing top-notch laboratory materials, keeping the devices humming, and coordinating
  the repairs and building of custom-designed laboratory equipment with the MIBA Machine
  shop.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
citation:
  ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics
    and physiology. 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:8657">10.15479/AT:ISTA:8657</a>'
  apa: 'Kavcic, B. (2020). <i>Perturbations of protein synthesis: from antibiotics
    to genetics and physiology</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT:ISTA:8657">https://doi.org/10.15479/AT:ISTA:8657</a>'
  chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
    Genetics and Physiology.” Institute of Science and Technology Austria, 2020. <a
    href="https://doi.org/10.15479/AT:ISTA:8657">https://doi.org/10.15479/AT:ISTA:8657</a>.'
  ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
    and physiology,” Institute of Science and Technology Austria, 2020.'
  ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
    and physiology. Institute of Science and Technology Austria.'
  mla: 'Kavcic, Bor. <i>Perturbations of Protein Synthesis: From Antibiotics to Genetics
    and Physiology</i>. Institute of Science and Technology Austria, 2020, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:8657">10.15479/AT:ISTA:8657</a>.'
  short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
    and Physiology, Institute of Science and Technology Austria, 2020.'
corr_author: '1'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2026-04-08T07:27:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
file:
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has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
  isbn:
  - 978-3-99078-011-4
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7673'
    relation: part_of_dissertation
    status: public
  - id: '8250'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2020'
...
---
_id: '8569'
abstract:
- lang: eng
  text: Concerted radial migration of newly born cortical projection neurons, from
    their birthplace to their final target lamina, is a key step in the assembly of
    the cerebral cortex. The cellular and molecular mechanisms regulating the specific
    sequential steps of radial neuronal migration in vivo are however still unclear,
    let alone the effects and interactions with the extracellular environment. In
    any in vivo context, cells will always be exposed to a complex extracellular environment
    consisting of (1) secreted factors acting as potential signaling cues, (2) the
    extracellular matrix, and (3) other cells providing cell–cell interaction through
    receptors and/or direct physical stimuli. Most studies so far have described and
    focused mainly on intrinsic cell-autonomous gene functions in neuronal migration
    but there is accumulating evidence that non-cell-autonomous-, local-, systemic-,
    and/or whole tissue-wide effects substantially contribute to the regulation of
    radial neuronal migration. These non-cell-autonomous effects may differentially
    affect cortical neuron migration in distinct cellular environments. However, the
    cellular and molecular natures of such non-cell-autonomous mechanisms are mostly
    unknown. Furthermore, physical forces due to collective migration and/or community
    effects (i.e., interactions with surrounding cells) may play important roles in
    neocortical projection neuron migration. In this concise review, we first outline
    distinct models of non-cell-autonomous interactions of cortical projection neurons
    along their radial migration trajectory during development. We then summarize
    experimental assays and platforms that can be utilized to visualize and potentially
    probe non-cell-autonomous mechanisms. Lastly, we define key questions to address
    in the future.
acknowledgement: AH was a recipient of a DOC Fellowship (24812) of the Austrian Academy
  of Sciences. This work also received support from IST Austria institutional funds;
  the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework
  Programme (FP7/2007–2013) under REA Grant Agreement No. 618444 to SH.
article_number: '574382'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Hansen AH, Hippenmeyer S. Non-cell-autonomous mechanisms in radial projection
    neuron migration in the developing cerebral cortex. <i>Frontiers in Cell and Developmental
    Biology</i>. 2020;8(9). doi:<a href="https://doi.org/10.3389/fcell.2020.574382">10.3389/fcell.2020.574382</a>
  apa: Hansen, A. H., &#38; Hippenmeyer, S. (2020). Non-cell-autonomous mechanisms
    in radial projection neuron migration in the developing cerebral cortex. <i>Frontiers
    in Cell and Developmental Biology</i>. Frontiers. <a href="https://doi.org/10.3389/fcell.2020.574382">https://doi.org/10.3389/fcell.2020.574382</a>
  chicago: Hansen, Andi H, and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms
    in Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers
    in Cell and Developmental Biology</i>. Frontiers, 2020. <a href="https://doi.org/10.3389/fcell.2020.574382">https://doi.org/10.3389/fcell.2020.574382</a>.
  ieee: A. H. Hansen and S. Hippenmeyer, “Non-cell-autonomous mechanisms in radial
    projection neuron migration in the developing cerebral cortex,” <i>Frontiers in
    Cell and Developmental Biology</i>, vol. 8, no. 9. Frontiers, 2020.
  ista: Hansen AH, Hippenmeyer S. 2020. Non-cell-autonomous mechanisms in radial projection
    neuron migration in the developing cerebral cortex. Frontiers in Cell and Developmental
    Biology. 8(9), 574382.
  mla: Hansen, Andi H., and Simon Hippenmeyer. “Non-Cell-Autonomous Mechanisms in
    Radial Projection Neuron Migration in the Developing Cerebral Cortex.” <i>Frontiers
    in Cell and Developmental Biology</i>, vol. 8, no. 9, 574382, Frontiers, 2020,
    doi:<a href="https://doi.org/10.3389/fcell.2020.574382">10.3389/fcell.2020.574382</a>.
  short: A.H. Hansen, S. Hippenmeyer, Frontiers in Cell and Developmental Biology
    8 (2020).
corr_author: '1'
date_created: 2020-09-26T06:11:07Z
date_published: 2020-09-25T00:00:00Z
date_updated: 2026-04-23T22:30:39Z
day: '25'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3389/fcell.2020.574382
ec_funded: 1
external_id:
  isi:
  - '000577915900001'
  pmid:
  - '33102480'
file:
- access_level: open_access
  checksum: 01f731824194c94c81a5da360d997073
  content_type: application/pdf
  creator: dernst
  date_created: 2020-09-28T13:11:17Z
  date_updated: 2020-09-28T13:11:17Z
  file_id: '8584'
  file_name: 2020_Frontiers_Hansen.pdf
  file_size: 5527139
  relation: main_file
  success: 1
file_date_updated: 2020-09-28T13:11:17Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular mechanisms of radial neuronal migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
publication: Frontiers in Cell and Developmental Biology
publication_identifier:
  issn:
  - 2296-634X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
related_material:
  record:
  - id: '9962'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Non-cell-autonomous mechanisms in radial projection neuron migration in the
  developing cerebral cortex
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2020'
...
---
_id: '8250'
abstract:
- lang: eng
  text: 'Antibiotics that interfere with translation, when combined, interact in diverse
    and difficult-to-predict ways. Here, we explain these interactions by “translation
    bottlenecks”: points in the translation cycle where antibiotics block ribosomal
    progression. To elucidate the underlying mechanisms of drug interactions between
    translation inhibitors, we generate translation bottlenecks genetically using
    inducible control of translation factors that regulate well-defined translation
    cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
    supporting that the interplay of different translation bottlenecks causes these
    interactions. We further show that growth laws, combined with drug uptake and
    binding kinetics, enable the direct prediction of a large fraction of observed
    interactions, yet fail to predict suppression. However, varying two translation
    bottlenecks simultaneously supports that dense traffic of ribosomes and competition
    for translation factors account for the previously unexplained suppression. These
    results highlight the importance of “continuous epistasis” in bacterial physiology.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
  Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
  comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
  which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
  many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
  the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
  We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
  Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
  work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
  27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
  T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
  and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
  (to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
article_processing_charge: No
article_type: original
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between
    translation-inhibiting antibiotics. <i>Nature Communications</i>. 2020;11. doi:<a
    href="https://doi.org/10.1038/s41467-020-17734-z">10.1038/s41467-020-17734-z</a>
  apa: Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). Mechanisms of drug
    interactions between translation-inhibiting antibiotics. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-020-17734-z">https://doi.org/10.1038/s41467-020-17734-z</a>
  chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
    Drug Interactions between Translation-Inhibiting Antibiotics.” <i>Nature Communications</i>.
    Springer Nature, 2020. <a href="https://doi.org/10.1038/s41467-020-17734-z">https://doi.org/10.1038/s41467-020-17734-z</a>.
  ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
    between translation-inhibiting antibiotics,” <i>Nature Communications</i>, vol.
    11. Springer Nature, 2020.
  ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
    translation-inhibiting antibiotics. Nature Communications. 11, 4013.
  mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
    Antibiotics.” <i>Nature Communications</i>, vol. 11, 4013, Springer Nature, 2020,
    doi:<a href="https://doi.org/10.1038/s41467-020-17734-z">10.1038/s41467-020-17734-z</a>.
  short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2026-04-23T22:30:38Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
  isi:
  - '000562769300008'
  pmid:
  - '32782250'
file:
- access_level: open_access
  checksum: 986bebb308850a55850028d3d2b5b664
  content_type: application/pdf
  creator: dernst
  date_created: 2020-08-17T07:36:57Z
  date_updated: 2020-08-17T07:36:57Z
  file_id: '8275'
  file_name: 2020_NatureComm_Kavcic.pdf
  file_size: 1965672
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  success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '8657'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Mechanisms of drug interactions between translation-inhibiting antibiotics
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: 11
year: '2020'
...
