---
_id: '14315'
abstract:
- lang: eng
  text: During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly
    demolish the nuclear pore complex. However, for poorly understood reasons, caspases
    are also activated during cell differentiation. Here, we show that sublethal activation
    of caspases during myogenesis results in the transient proteolysis of four peripheral
    Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective,
    and we identified in an unbiased manner several classes of cytoplasmic, plasma
    membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC
    trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic
    reticulum stress. Our results suggest that caspases can reversibly modulate nuclear
    transport activity, which allows them to function as agents of cell differentiation
    and adaptation at sublethal levels.
acknowledgement: 'We thank the members of the Hetzer laboratory, Tony Hunter (Salk),
  Lorenzo Puri (Sanford Burnham Prebys), and Jongmin Kim (Massachusetts General Hospital)
  for the critical reading of the manuscript; Kenneth Diffenderfer and Aimee Pankonin
  (Stem Cell Core at the Salk Institute) for help with neurogenesis; Carol Marchetto
  and Fred Gage (Salk) for providing H9 embryonic stem cells; Lorenzo Puri, Alexandra
  Sacco, and Luca Caputo (Sanford Burnham Prebys) for helpful discussions and sharing
  mouse primary myoblasts. This work was supported by a Glenn Foundation for Medical
  Research Postdoctoral Fellowship in Aging Research (UHC), the NOMIS foundation (MWH),
  and the National Institutes of Health (R01 NS096786 to MWH and K01 AR080828 to UHC).
  This work was also supported by the Mass Spectrometry Core of the Salk Institute
  with funding from NIH-NCI CCSG: P30 014195 and the Helmsley Center for Genomic Medicine.
  We thank Jolene Diedrich and Antonio Pinto for technical support.'
article_number: RP89066
article_processing_charge: Yes
article_type: original
author:
- first_name: Ukrae H.
  full_name: Cho, Ukrae H.
  last_name: Cho
- first_name: Martin W
  full_name: Hetzer, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: Hetzer
  orcid: 0000-0002-2111-992X
citation:
  ama: Cho UH, Hetzer M. Caspase-mediated nuclear pore complex trimming in cell differentiation
    and endoplasmic reticulum stress. <i>eLife</i>. 2023;12. doi:<a href="https://doi.org/10.7554/eLife.89066">10.7554/eLife.89066</a>
  apa: Cho, U. H., &#38; Hetzer, M. (2023). Caspase-mediated nuclear pore complex
    trimming in cell differentiation and endoplasmic reticulum stress. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.89066">https://doi.org/10.7554/eLife.89066</a>
  chicago: Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex
    Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>.
    eLife Sciences Publications, 2023. <a href="https://doi.org/10.7554/eLife.89066">https://doi.org/10.7554/eLife.89066</a>.
  ieee: U. H. Cho and M. Hetzer, “Caspase-mediated nuclear pore complex trimming in
    cell differentiation and endoplasmic reticulum stress,” <i>eLife</i>, vol. 12.
    eLife Sciences Publications, 2023.
  ista: Cho UH, Hetzer M. 2023. Caspase-mediated nuclear pore complex trimming in
    cell differentiation and endoplasmic reticulum stress. eLife. 12, RP89066.
  mla: Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming
    in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>, vol.
    12, RP89066, eLife Sciences Publications, 2023, doi:<a href="https://doi.org/10.7554/eLife.89066">10.7554/eLife.89066</a>.
  short: U.H. Cho, M. Hetzer, ELife 12 (2023).
date_created: 2023-09-10T22:01:11Z
date_published: 2023-09-04T00:00:00Z
date_updated: 2023-09-15T07:07:10Z
day: '04'
ddc:
- '570'
department:
- _id: MaHe
doi: 10.7554/eLife.89066
external_id:
  pmid:
  - '37665327'
file:
- access_level: open_access
  checksum: db24bf3d595507387b48d3799c33e289
  content_type: application/pdf
  creator: dernst
  date_created: 2023-09-15T06:59:10Z
  date_updated: 2023-09-15T06:59:10Z
  file_id: '14336'
  file_name: 2023_eLife_Cho.pdf
  file_size: 3703097
  relation: main_file
  success: 1
file_date_updated: 2023-09-15T06:59:10Z
has_accepted_license: '1'
intvolume: '        12'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Caspase-mediated nuclear pore complex trimming in cell differentiation and
  endoplasmic reticulum stress
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2023'
...
---
_id: '13316'
abstract:
- lang: eng
  text: Although budding yeast has been extensively used as a model organism for studying
    organelle functions and intracellular vesicle trafficking, whether it possesses
    an independent endocytic early/sorting compartment that sorts endocytic cargos
    to the endo-lysosomal pathway or the recycling pathway has long been unclear.
    The structure and properties of the endocytic early/sorting compartment differ
    significantly between organisms; in plant cells, the trans-Golgi network (TGN)
    serves this role, whereas in mammalian cells a separate intracellular structure
    performs this function. The yeast syntaxin homolog Tlg2p, widely localizing to
    the TGN and endosomal compartments, is presumed to act as a Q-SNARE for endocytic
    vesicles, but which compartment is the direct target for endocytic vesicles remained
    unanswered. Here we demonstrate by high-speed and high-resolution 4D imaging of
    fluorescently labeled endocytic cargos that the Tlg2p-residing compartment within
    the TGN functions as the early/sorting compartment. After arriving here, endocytic
    cargos are recycled to the plasma membrane or transported to the yeast Rab5-residing
    endosomal compartment through the pathway requiring the clathrin adaptors GGAs.
    Interestingly, Gga2p predominantly localizes at the Tlg2p-residing compartment,
    and the deletion of GGAs has little effect on another TGN region where Sec7p is
    present but suppresses dynamics of the Tlg2-residing early/sorting compartment,
    indicating that the Tlg2p- and Sec7p-residing regions are discrete entities in
    the mutant. Thus, the Tlg2p-residing region seems to serve as an early/sorting
    compartment and function independently of the Sec7p-residing region within the
    TGN.
acknowledgement: 'This work was supported by JSPS KAKENHI grant #18K062291, and the
  Takeda Science Foundation to JYT., as well as JSPS KAKENHI grant #19K065710, the
  Takeda Science Foundation, and Life Science Foundation of Japan to JT.'
article_number: e84850
article_processing_charge: Yes
article_type: original
author:
- first_name: Junko Y.
  full_name: Toshima, Junko Y.
  last_name: Toshima
- first_name: Ayana
  full_name: Tsukahara, Ayana
  last_name: Tsukahara
- first_name: Makoto
  full_name: Nagano, Makoto
  last_name: Nagano
- first_name: Takuro
  full_name: Tojima, Takuro
  last_name: Tojima
- first_name: Daria E
  full_name: Siekhaus, Daria E
  id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
  last_name: Siekhaus
  orcid: 0000-0001-8323-8353
- first_name: Akihiko
  full_name: Nakano, Akihiko
  last_name: Nakano
- first_name: Jiro
  full_name: Toshima, Jiro
  last_name: Toshima
citation:
  ama: Toshima JY, Tsukahara A, Nagano M, et al. The yeast endocytic early/sorting
    compartment exists as an independent sub-compartment within the trans-Golgi network.
    <i>eLife</i>. 2023;12. doi:<a href="https://doi.org/10.7554/eLife.84850">10.7554/eLife.84850</a>
  apa: Toshima, J. Y., Tsukahara, A., Nagano, M., Tojima, T., Siekhaus, D. E., Nakano,
    A., &#38; Toshima, J. (2023). The yeast endocytic early/sorting compartment exists
    as an independent sub-compartment within the trans-Golgi network. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.84850">https://doi.org/10.7554/eLife.84850</a>
  chicago: Toshima, Junko Y., Ayana Tsukahara, Makoto Nagano, Takuro Tojima, Daria
    E Siekhaus, Akihiko Nakano, and Jiro Toshima. “The Yeast Endocytic Early/Sorting
    Compartment Exists as an Independent Sub-Compartment within the Trans-Golgi Network.”
    <i>ELife</i>. eLife Sciences Publications, 2023. <a href="https://doi.org/10.7554/eLife.84850">https://doi.org/10.7554/eLife.84850</a>.
  ieee: J. Y. Toshima <i>et al.</i>, “The yeast endocytic early/sorting compartment
    exists as an independent sub-compartment within the trans-Golgi network,” <i>eLife</i>,
    vol. 12. eLife Sciences Publications, 2023.
  ista: Toshima JY, Tsukahara A, Nagano M, Tojima T, Siekhaus DE, Nakano A, Toshima
    J. 2023. The yeast endocytic early/sorting compartment exists as an independent
    sub-compartment within the trans-Golgi network. eLife. 12, e84850.
  mla: Toshima, Junko Y., et al. “The Yeast Endocytic Early/Sorting Compartment Exists
    as an Independent Sub-Compartment within the Trans-Golgi Network.” <i>ELife</i>,
    vol. 12, e84850, eLife Sciences Publications, 2023, doi:<a href="https://doi.org/10.7554/eLife.84850">10.7554/eLife.84850</a>.
  short: J.Y. Toshima, A. Tsukahara, M. Nagano, T. Tojima, D.E. Siekhaus, A. Nakano,
    J. Toshima, ELife 12 (2023).
date_created: 2023-07-30T22:01:02Z
date_published: 2023-07-21T00:00:00Z
date_updated: 2023-12-13T11:37:36Z
day: '21'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.7554/eLife.84850
external_id:
  isi:
  - '001035372800001'
  pmid:
  - '37477116'
file:
- access_level: open_access
  checksum: 2af111a00cf5e3a956f7f0fd13199b15
  content_type: application/pdf
  creator: dernst
  date_created: 2023-07-31T07:43:00Z
  date_updated: 2023-07-31T07:43:00Z
  file_id: '13324'
  file_name: 2023_eLife_Toshima.pdf
  file_size: 11980913
  relation: main_file
  success: 1
file_date_updated: 2023-07-31T07:43:00Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: The yeast endocytic early/sorting compartment exists as an independent sub-compartment
  within the trans-Golgi network
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2023'
...
---
_id: '10736'
abstract:
- lang: eng
  text: Predicting function from sequence is a central problem of biology. Currently,
    this is possible only locally in a narrow mutational neighborhood around a wildtype
    sequence rather than globally from any sequence. Using random mutant libraries,
    we developed a biophysical model that accounts for multiple features of σ70 binding
    bacterial promoters to predict constitutive gene expression levels from any sequence.
    We experimentally and theoretically estimated that 10–20% of random sequences
    lead to expression and ~80% of non-expressing sequences are one mutation away
    from a functional promoter. The potential for generating expression from random
    sequences is so pervasive that selection acts against σ70-RNA polymerase binding
    sites even within inter-genic, promoter-containing regions. This pervasiveness
    of σ70-binding sites implies that emergence of promoters is not the limiting step
    in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter
    function into a mechanistic model enabled not only more accurate predictions of
    gene expression levels, but also identified that promoters evolve more rapidly
    than previously thought.
acknowledgement: 'We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao,
  Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on
  the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded
  by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML;
  IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme
  7 (2007–2013, grant agreement number 648440) to JPB.'
article_number: e64543
article_processing_charge: No
article_type: original
author:
- first_name: Mato
  full_name: Lagator, Mato
  id: 345D25EC-F248-11E8-B48F-1D18A9856A87
  last_name: Lagator
- first_name: Srdjan
  full_name: Sarikas, Srdjan
  id: 35F0286E-F248-11E8-B48F-1D18A9856A87
  last_name: Sarikas
- first_name: Magdalena
  full_name: Steinrueck, Magdalena
  last_name: Steinrueck
- first_name: David
  full_name: Toledo-Aparicio, David
  last_name: Toledo-Aparicio
- first_name: Jonathan P
  full_name: Bollback, Jonathan P
  id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
  last_name: Bollback
  orcid: 0000-0002-4624-4612
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
citation:
  ama: Lagator M, Sarikas S, Steinrueck M, et al. Predicting bacterial promoter function
    and evolution from random sequences. <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/eLife.64543">10.7554/eLife.64543</a>
  apa: Lagator, M., Sarikas, S., Steinrueck, M., Toledo-Aparicio, D., Bollback, J.
    P., Guet, C. C., &#38; Tkačik, G. (2022). Predicting bacterial promoter function
    and evolution from random sequences. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.64543">https://doi.org/10.7554/eLife.64543</a>
  chicago: Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, David Toledo-Aparicio,
    Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter
    Function and Evolution from Random Sequences.” <i>ELife</i>. eLife Sciences Publications,
    2022. <a href="https://doi.org/10.7554/eLife.64543">https://doi.org/10.7554/eLife.64543</a>.
  ieee: M. Lagator <i>et al.</i>, “Predicting bacterial promoter function and evolution
    from random sequences,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.
  ista: Lagator M, Sarikas S, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC,
    Tkačik G. 2022. Predicting bacterial promoter function and evolution from random
    sequences. eLife. 11, e64543.
  mla: Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution
    from Random Sequences.” <i>ELife</i>, vol. 11, e64543, eLife Sciences Publications,
    2022, doi:<a href="https://doi.org/10.7554/eLife.64543">10.7554/eLife.64543</a>.
  short: M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback,
    C.C. Guet, G. Tkačik, ELife 11 (2022).
date_created: 2022-02-06T23:01:32Z
date_published: 2022-01-26T00:00:00Z
date_updated: 2023-08-02T14:09:02Z
day: '26'
ddc:
- '576'
department:
- _id: CaGu
- _id: GaTk
- _id: NiBa
doi: 10.7554/eLife.64543
ec_funded: 1
external_id:
  isi:
  - '000751104400001'
  pmid:
  - '35080492'
file:
- access_level: open_access
  checksum: decdcdf600ff51e9a9703b49ca114170
  content_type: application/pdf
  creator: cchlebak
  date_created: 2022-02-07T07:14:09Z
  date_updated: 2022-02-07T07:14:09Z
  file_id: '10739'
  file_name: 2022_ELife_Lagator.pdf
  file_size: 5604343
  relation: main_file
  success: 1
file_date_updated: 2022-02-07T07:14:09Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Predicting bacterial promoter function and evolution from random sequences
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: 11
year: '2022'
...
---
_id: '11419'
abstract:
- lang: eng
  text: Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in
    Alzheimer’s disease. We addressed whether tau elevation affects synaptic transmission
    at the calyx of Held in slices from mice brainstem. Whole-cell loading of WT human
    tau (h-tau) in presynaptic terminals at 10–20 µM caused microtubule (MT) assembly
    and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements
    revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking
    MT assembly using nocodazole prevented tau-induced impairments of endocytosis
    and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly
    by WT h-tau loading was associated with an increased MT-bound fraction of the
    endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin
    1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced
    impairments of endocytosis and neurotransmission. We conclude that elevation of
    presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free
    dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired,
    causing activity-dependent rundown of neurotransmission.
acknowledgement: We thank Yasuo Ihara, Nobuyuki Nukina, and Takeshi Sakaba for comments
  and Patrick Stoney for editing this paper. We also thank Shota Okuda and Mikako
  Matsubara for their contributions in the early stage of this study, and Satoko Wada-Kakuda
  for technical assistant with in vitro analysis of tau. This research was supported
  by funding from Okinawa Institute of Science and Technology and from Technology
  (OIST) and Core Research for the Evolutional Science and Technology of Japan Science
  and Technology Agency (CREST) to TT, and by Scientific Research on Innovative Areas
  to TM (Brain Protein Aging and Dementia Control 26117004).
article_number: e73542
article_processing_charge: No
article_type: original
author:
- first_name: Tetsuya
  full_name: Hori, Tetsuya
  last_name: Hori
- first_name: Kohgaku
  full_name: Eguchi, Kohgaku
  id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
  last_name: Eguchi
  orcid: 0000-0002-6170-2546
- first_name: Han Ying
  full_name: Wang, Han Ying
  last_name: Wang
- first_name: Tomohiro
  full_name: Miyasaka, Tomohiro
  last_name: Miyasaka
- first_name: Laurent
  full_name: Guillaud, Laurent
  last_name: Guillaud
- first_name: Zacharie
  full_name: Taoufiq, Zacharie
  last_name: Taoufiq
- first_name: Satyajit
  full_name: Mahapatra, Satyajit
  last_name: Mahapatra
- first_name: Hiroshi
  full_name: Yamada, Hiroshi
  last_name: Yamada
- first_name: Kohji
  full_name: Takei, Kohji
  last_name: Takei
- first_name: Tomoyuki
  full_name: Takahashi, Tomoyuki
  last_name: Takahashi
citation:
  ama: Hori T, Eguchi K, Wang HY, et al. Microtubule assembly by tau impairs endocytosis
    and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse
    model. <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/eLife.73542">10.7554/eLife.73542</a>
  apa: Hori, T., Eguchi, K., Wang, H. Y., Miyasaka, T., Guillaud, L., Taoufiq, Z.,
    … Takahashi, T. (2022). Microtubule assembly by tau impairs endocytosis and neurotransmission
    via dynamin sequestration in Alzheimer’s disease synapse model. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.73542">https://doi.org/10.7554/eLife.73542</a>
  chicago: Hori, Tetsuya, Kohgaku Eguchi, Han Ying Wang, Tomohiro Miyasaka, Laurent
    Guillaud, Zacharie Taoufiq, Satyajit Mahapatra, Hiroshi Yamada, Kohji Takei, and
    Tomoyuki Takahashi. “Microtubule Assembly by Tau Impairs Endocytosis and Neurotransmission
    via Dynamin Sequestration in Alzheimer’s Disease Synapse Model.” <i>ELife</i>.
    eLife Sciences Publications, 2022. <a href="https://doi.org/10.7554/eLife.73542">https://doi.org/10.7554/eLife.73542</a>.
  ieee: T. Hori <i>et al.</i>, “Microtubule assembly by tau impairs endocytosis and
    neurotransmission via dynamin sequestration in Alzheimer’s disease synapse model,”
    <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.
  ista: Hori T, Eguchi K, Wang HY, Miyasaka T, Guillaud L, Taoufiq Z, Mahapatra S,
    Yamada H, Takei K, Takahashi T. 2022. Microtubule assembly by tau impairs endocytosis
    and neurotransmission via dynamin sequestration in Alzheimer’s disease synapse
    model. eLife. 11, e73542.
  mla: Hori, Tetsuya, et al. “Microtubule Assembly by Tau Impairs Endocytosis and
    Neurotransmission via Dynamin Sequestration in Alzheimer’s Disease Synapse Model.”
    <i>ELife</i>, vol. 11, e73542, eLife Sciences Publications, 2022, doi:<a href="https://doi.org/10.7554/eLife.73542">10.7554/eLife.73542</a>.
  short: T. Hori, K. Eguchi, H.Y. Wang, T. Miyasaka, L. Guillaud, Z. Taoufiq, S. Mahapatra,
    H. Yamada, K. Takei, T. Takahashi, ELife 11 (2022).
date_created: 2022-05-29T22:01:54Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2023-08-03T07:15:49Z
day: '05'
ddc:
- '616'
department:
- _id: RySh
doi: 10.7554/eLife.73542
external_id:
  isi:
  - '000876231600001'
  pmid:
  - '35471147 '
file:
- access_level: open_access
  checksum: ccddbd167e00ff8375f12998af497152
  content_type: application/pdf
  creator: cchlebak
  date_created: 2022-05-30T08:09:16Z
  date_updated: 2022-05-30T08:09:16Z
  file_id: '11421'
  file_name: elife-73542-v2.pdf
  file_size: 2466296
  relation: main_file
  success: 1
file_date_updated: 2022-05-30T08:09:16Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin
  sequestration in Alzheimer's disease synapse model
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: 11
year: '2022'
...
---
_id: '11843'
abstract:
- lang: eng
  text: A key attribute of persistent or recurring bacterial infections is the ability
    of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
    type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
    establish persistent infections. However, the molecular mechanisms and strategies
    by which bacteria actively circumvent the immune response of the host remain poorly
    understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
    detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein
    located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids
    involved in CD14 binding are highly conserved across pathogenic and non-pathogenic
    strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration
    by overactivation of integrins and blunted expression of co-stimulatory molecules
    by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both
    rate-limiting factors of T cell activation. This response was binary at the single-cell
    level, but averaged in larger populations exposed to both piliated and non-piliated
    pathogens, presumably via the exchange of immunomodulatory cytokines. While defining
    an active molecular mechanism of immune evasion by pathogens, the interaction
    between FimH and CD14 represents a potential target to interfere with persistent
    and recurrent infections, such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89,
  and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and
  Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and
  Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific
  Service Units, especially the Bioimaging facility, the Preclinical facility and
  the Electron microscopy facility for technical support, Jakob Wallner and all members
  of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically
  reading the manuscript. This work was supported by grants from the Austrian Research
  Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373),
  and the Austrian Science Fund (FWF P29911) to MS.
article_number: e78995
article_processing_charge: Yes
article_type: original
author:
- first_name: Kathrin
  full_name: Tomasek, Kathrin
  id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
  last_name: Tomasek
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
- first_name: Ivana
  full_name: Glatzová, Ivana
  id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
  last_name: Glatzová
- first_name: Michael S.
  full_name: Lukesch, Michael S.
  last_name: Lukesch
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
    uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
    <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/eLife.78995">10.7554/eLife.78995</a>
  apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38;
    Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the
    host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.78995">https://doi.org/10.7554/eLife.78995</a>
  chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
    Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
    Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences
    Publications, 2022. <a href="https://doi.org/10.7554/eLife.78995">https://doi.org/10.7554/eLife.78995</a>.
  ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
    K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
    response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications,
    2022.
  ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type
    1 piliated uropathogenic Escherichia coli hijack the host immune response by binding
    to CD14. eLife. 11, e78995.
  mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
    the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife
    Sciences Publications, 2022, doi:<a href="https://doi.org/10.7554/eLife.78995">10.7554/eLife.78995</a>.
  short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
    ELife 11 (2022).
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2023-08-03T12:54:21Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
  isi:
  - '000838410200001'
file:
- access_level: open_access
  checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4
  content_type: application/pdf
  creator: cchlebak
  date_created: 2022-08-16T08:57:37Z
  date_updated: 2022-08-16T08:57:37Z
  file_id: '11861'
  file_name: 2022_eLife_Tomasek.pdf
  file_size: 2057577
  relation: main_file
  success: 1
file_date_updated: 2022-08-16T08:57:37Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29911
  name: Mechanical adaptation of lamellipodial actin
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  record:
  - id: '10316'
    relation: earlier_version
    status: public
scopus_import: '1'
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
  by binding to CD14
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: 11
year: '2022'
...
---
_id: '12157'
abstract:
- lang: eng
  text: 'Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood.
    Here, we model this process analytically, in the plausible setting of a highly
    polygenic, quantitative trait that experiences a sudden shift in the fitness optimum.
    We show how the mean phenotype changes over time, depending on the effect sizes
    of loci that contribute to variance in the trait, and characterize the allele
    dynamics at these loci. Notably, we describe the two phases of the allele dynamics:
    The first is a rapid phase, in which directional selection introduces small frequency
    differences between alleles whose effects are aligned with or opposed to the shift,
    ultimately leading to small differences in their probability of fixation during
    a second, longer phase, governed by stabilizing selection. As we discuss, key
    results should hold in more general settings and have important implications for
    efforts to identify the genetic basis of adaptation in humans and other species.'
acknowledgement: "We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and
  Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim
  Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel
  and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health
  GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372
  Laura Katharine Hayward"
article_number: '66697'
article_processing_charge: No
article_type: original
author:
- first_name: Laura
  full_name: Hayward, Laura
  id: fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b
  last_name: Hayward
- first_name: Guy
  full_name: Sella, Guy
  last_name: Sella
citation:
  ama: Hayward L, Sella G. Polygenic adaptation after a sudden change in environment.
    <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/elife.66697">10.7554/elife.66697</a>
  apa: Hayward, L., &#38; Sella, G. (2022). Polygenic adaptation after a sudden change
    in environment. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.66697">https://doi.org/10.7554/elife.66697</a>
  chicago: Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change
    in Environment.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href="https://doi.org/10.7554/elife.66697">https://doi.org/10.7554/elife.66697</a>.
  ieee: L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,”
    <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.
  ista: Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment.
    eLife. 11, 66697.
  mla: Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change
    in Environment.” <i>ELife</i>, vol. 11, 66697, eLife Sciences Publications, 2022,
    doi:<a href="https://doi.org/10.7554/elife.66697">10.7554/elife.66697</a>.
  short: L. Hayward, G. Sella, ELife 11 (2022).
date_created: 2023-01-12T12:09:00Z
date_published: 2022-09-26T00:00:00Z
date_updated: 2023-08-04T09:04:58Z
day: '26'
ddc:
- '570'
department:
- _id: NiBa
doi: 10.7554/elife.66697
external_id:
  isi:
  - '000890735600001'
file:
- access_level: open_access
  checksum: 28de155b231ac1c8d4501c98b2fb359a
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-24T12:21:32Z
  date_updated: 2023-01-24T12:21:32Z
  file_id: '12363'
  file_name: 2022_eLife_Hayward.pdf
  file_size: 18935612
  relation: main_file
  success: 1
file_date_updated: 2023-01-24T12:21:32Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Polygenic adaptation after a sudden change in environment
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: 11
year: '2022'
...
---
_id: '12288'
abstract:
- lang: eng
  text: To understand the function of neuronal circuits, it is crucial to disentangle
    the connectivity patterns within the network. However, most tools currently used
    to explore connectivity have low throughput, low selectivity, or limited accessibility.
    Here, we report the development of an improved packaging system for the production
    of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers
    orders of magnitude higher with no background contamination, at a fraction of
    the production time, while preserving the efficiency of transsynaptic labeling.
    Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic
    RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal
    populations, tailored for diverse experimental requirements. We demonstrate the
    power and flexibility of the new system by uncovering hidden local and distal
    inhibitory connections in the mouse hippocampal formation and by imaging the functional
    properties of a cortical microcircuit across weeks. Our novel production pipeline
    provides a convenient approach to generate new rabies vectors, while our toolkit
    flexibly and efficiently expands the current capacity to label, manipulate and
    image the neuronal activity of interconnected neuronal circuits in vitro and in
    vivo.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c
  viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript.
  This research was supported by the Scientific Service Units (SSU) of IST-Austria
  through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical
  Facility (PCF). This project was funded by the European Research Council (ERC) under
  the European Union’s Horizon 2020 research and innovation programme (ERC advanced
  grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der
  Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier
  Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).
article_number: '79848'
article_processing_charge: No
article_type: original
author:
- first_name: Anton L
  full_name: Sumser, Anton L
  id: 3320A096-F248-11E8-B48F-1D18A9856A87
  last_name: Sumser
  orcid: 0000-0002-4792-1881
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
citation:
  ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production
    of improved rabies viral vectors for specific, efficient and versatile transsynaptic
    retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/elife.79848">10.7554/elife.79848</a>
  apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast,
    high-throughput production of improved rabies viral vectors for specific, efficient
    and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences
    Publications. <a href="https://doi.org/10.7554/elife.79848">https://doi.org/10.7554/elife.79848</a>
  chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon.
    “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific,
    Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife
    Sciences Publications, 2022. <a href="https://doi.org/10.7554/elife.79848">https://doi.org/10.7554/elife.79848</a>.
  ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput
    production of improved rabies viral vectors for specific, efficient and versatile
    transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications,
    2022.
  ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production
    of improved rabies viral vectors for specific, efficient and versatile transsynaptic
    retrograde labeling. eLife. 11, 79848.
  mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies
    Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.”
    <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href="https://doi.org/10.7554/elife.79848">10.7554/elife.79848</a>.
  short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).
date_created: 2023-01-16T10:04:15Z
date_published: 2022-09-15T00:00:00Z
date_updated: 2023-08-04T10:29:48Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PeJo
doi: 10.7554/elife.79848
ec_funded: 1
external_id:
  isi:
  - '000892204300001'
  pmid:
  - '36040301'
file:
- access_level: open_access
  checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T11:50:53Z
  date_updated: 2023-01-30T11:50:53Z
  file_id: '12463'
  file_name: 2022_eLife_Sumser.pdf
  file_size: 8506811
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T11:50:53Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: 266D407A-B435-11E9-9278-68D0E5697425
  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
    colliculus
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast, high-throughput production of improved rabies viral vectors for specific,
  efficient and versatile transsynaptic retrograde labeling
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: 11
year: '2022'
...
---
_id: '12333'
abstract:
- lang: eng
  text: Together, copy-number and point mutations form the basis for most evolutionary
    novelty, through the process of gene duplication and divergence. While a plethora
    of genomic data reveals the long-term fate of diverging coding sequences and their
    cis-regulatory elements, little is known about the early dynamics around the duplication
    event itself. In microorganisms, selection for increased gene expression often
    drives the expansion of gene copy-number mutations, which serves as a crude adaptation,
    prior to divergence through refining point mutations. Using a simple synthetic
    genetic reporter system that can distinguish between copy-number and point mutations,
    we study their early and transient adaptive dynamics in real time in Escherichia
    coli. We find two qualitatively different routes of adaptation, depending on the
    level of functional improvement needed. In conditions of high gene expression
    demand, the two mutation types occur as a combination. However, under low gene
    expression demand, copy-number and point mutations are mutually exclusive; here,
    owing to their higher frequency, adaptation is dominated by copy-number mutations,
    in a process we term amplification hindrance. Ultimately, due to high reversal
    rates and pleiotropic cost, copy-number mutations may not only serve as a crude
    and transient adaptation, but also constrain sequence divergence over evolutionary
    time scales.
acknowledgement: "We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska,
  R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek
  for help with flow cytometry."
article_number: e82240
article_processing_charge: No
article_type: original
author:
- first_name: Isabella
  full_name: Tomanek, Isabella
  id: 3981F020-F248-11E8-B48F-1D18A9856A87
  last_name: Tomanek
  orcid: 0000-0001-6197-363X
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Tomanek I, Guet CC. Adaptation dynamics between copynumber and point mutations.
    <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/ELIFE.82240">10.7554/ELIFE.82240</a>
  apa: Tomanek, I., &#38; Guet, C. C. (2022). Adaptation dynamics between copynumber
    and point mutations. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/ELIFE.82240">https://doi.org/10.7554/ELIFE.82240</a>
  chicago: Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber
    and Point Mutations.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href="https://doi.org/10.7554/ELIFE.82240">https://doi.org/10.7554/ELIFE.82240</a>.
  ieee: I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point
    mutations,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.
  ista: Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point
    mutations. eLife. 11, e82240.
  mla: Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber
    and Point Mutations.” <i>ELife</i>, vol. 11, e82240, eLife Sciences Publications,
    2022, doi:<a href="https://doi.org/10.7554/ELIFE.82240">10.7554/ELIFE.82240</a>.
  short: I. Tomanek, C.C. Guet, ELife 11 (2022).
date_created: 2023-01-22T23:00:55Z
date_published: 2022-12-22T00:00:00Z
date_updated: 2023-08-03T14:23:07Z
day: '22'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.7554/ELIFE.82240
external_id:
  isi:
  - '000912674700001'
file:
- access_level: open_access
  checksum: 9321fd5f06ff59d5e2d33daee84b3da1
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-23T08:56:21Z
  date_updated: 2023-01-23T08:56:21Z
  file_id: '12338'
  file_name: 2022_eLife_Tomanek.pdf
  file_size: 8835954
  relation: main_file
  success: 1
file_date_updated: 2023-01-23T08:56:21Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://doi.org/10.5281/zenodo.6974122
  record:
  - id: '12339'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Adaptation dynamics between copynumber and point mutations
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: 11
year: '2022'
...
---
_id: '9243'
abstract:
- lang: eng
  text: Peptidoglycan is an essential component of the bacterial cell envelope that
    surrounds the cytoplasmic membrane to protect the cell from osmotic lysis. Important
    antibiotics such as β-lactams and glycopeptides target peptidoglycan biosynthesis.
    Class A penicillin-binding proteins (PBPs) are bifunctional membrane-bound peptidoglycan
    synthases that polymerize glycan chains and connect adjacent stem peptides by
    transpeptidation. How these enzymes work in their physiological membrane environment
    is poorly understood. Here, we developed a novel Förster resonance energy transfer-based
    assay to follow in real time both reactions of class A PBPs reconstituted in liposomes
    or supported lipid bilayers and applied this assay with PBP1B homologues from
    Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii in the presence
    or absence of their cognate lipoprotein activator. Our assay will allow unravelling
    the mechanisms of peptidoglycan synthesis in a lipid-bilayer environment and can
    be further developed to be used for high-throughput screening for new antimicrobials.
acknowledgement: 'We thank Alexander Egan (Newcastle University) for purified proteins
  LpoB(sol) and LpoPPa(sol), Federico Corona (Newcastle University) for purified MepM,
  and Oliver Birkholz and Jacob Piehler (Department of Biology and Center of Cellular
  Nanoanalytics, University of Osnabru¨ ck) for their help with PBP1B reconstitution
  into polymer-SLBs and initial guidance on single particle tracking. We also acknowledge
  Christian P Richter and Changjiang You (Department of Biology and Center of Cellular
  Nanoanalytics, University of Osnabru¨ ck) for providing SLIMfast software and tris-DODA-NTA
  reagent, respectively. This work was funded by the BBSRC grant BB/R017409/1 (to
  WV), the European Research Council through grant ERC-2015-StG-679239 (to ML), and
  long-term fellowships HFSP LT 000824/2016-L4 and EMBO ALTF 1163–2015 (to NB). '
article_number: 1-32
article_processing_charge: No
article_type: original
author:
- first_name: Víctor M.
  full_name: Hernández-Rocamora, Víctor M.
  last_name: Hernández-Rocamora
- 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: Katharina
  full_name: Peters, Katharina
  last_name: Peters
- first_name: Eefjan
  full_name: Breukink, Eefjan
  last_name: Breukink
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
- first_name: Waldemar
  full_name: Vollmer, Waldemar
  last_name: Vollmer
citation:
  ama: Hernández-Rocamora VM, Baranova NS, Peters K, Breukink E, Loose M, Vollmer
    W. Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin
    binding proteins. <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/eLife.61525">10.7554/eLife.61525</a>
  apa: Hernández-Rocamora, V. M., Baranova, N. S., Peters, K., Breukink, E., Loose,
    M., &#38; Vollmer, W. (2021). Real time monitoring of peptidoglycan synthesis
    by membrane-reconstituted penicillin binding proteins. <i>ELife</i>. eLife Sciences
    Publications. <a href="https://doi.org/10.7554/eLife.61525">https://doi.org/10.7554/eLife.61525</a>
  chicago: Hernández-Rocamora, Víctor M., Natalia S. Baranova, Katharina Peters, Eefjan
    Breukink, Martin Loose, and Waldemar Vollmer. “Real Time Monitoring of Peptidoglycan
    Synthesis by Membrane-Reconstituted Penicillin Binding Proteins.” <i>ELife</i>.
    eLife Sciences Publications, 2021. <a href="https://doi.org/10.7554/eLife.61525">https://doi.org/10.7554/eLife.61525</a>.
  ieee: V. M. Hernández-Rocamora, N. S. Baranova, K. Peters, E. Breukink, M. Loose,
    and W. Vollmer, “Real time monitoring of peptidoglycan synthesis by membrane-reconstituted
    penicillin binding proteins,” <i>eLife</i>, vol. 10. eLife Sciences Publications,
    2021.
  ista: Hernández-Rocamora VM, Baranova NS, Peters K, Breukink E, Loose M, Vollmer
    W. 2021. Real time monitoring of peptidoglycan synthesis by membrane-reconstituted
    penicillin binding proteins. eLife. 10, 1–32.
  mla: Hernández-Rocamora, Víctor M., et al. “Real Time Monitoring of Peptidoglycan
    Synthesis by Membrane-Reconstituted Penicillin Binding Proteins.” <i>ELife</i>,
    vol. 10, 1–32, eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/eLife.61525">10.7554/eLife.61525</a>.
  short: V.M. Hernández-Rocamora, N.S. Baranova, K. Peters, E. Breukink, M. Loose,
    W. Vollmer, ELife 10 (2021).
date_created: 2021-03-14T23:01:33Z
date_published: 2021-02-24T00:00:00Z
date_updated: 2023-08-07T14:10:50Z
day: '24'
ddc:
- '570'
department:
- _id: MaLo
doi: 10.7554/eLife.61525
ec_funded: 1
external_id:
  isi:
  - '000627596400001'
file:
- access_level: open_access
  checksum: 79897a09bfecd9914d39c4aea2841855
  content_type: application/pdf
  creator: dernst
  date_created: 2021-03-22T07:36:08Z
  date_updated: 2021-03-22T07:36:08Z
  file_id: '9268'
  file_name: 2021_eLife_HernandezRocamora.pdf
  file_size: 2314698
  relation: main_file
  success: 1
file_date_updated: 2021-03-22T07:36:08Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '679239'
  name: Self-Organization of the Bacterial Cell
- _id: 2596EAB6-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 2015-1163
  name: Synthesis of bacterial cell wall
- _id: 259B655A-B435-11E9-9278-68D0E5697425
  grant_number: LT000824/2016
  name: Reconstitution of bacterial cell wall sythesis
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin
  binding proteins
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: 10
year: '2021'
...
---
_id: '9437'
abstract:
- lang: eng
  text: The synaptic connection from medial habenula (MHb) to interpeduncular nucleus
    (IPN) is critical for emotion-related behaviors and uniquely expresses R-type
    Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel
    tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates
    or inhibits transmitter release from MHb terminals depending on the IPN subnucleus,
    but the role of KCTDs is unknown. We therefore examined the localization and function
    of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells
    that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3
    currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3
    co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional
    modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase
    of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3
    with KCTDs therefore scales synaptic strength independent of GBR activation.
acknowledgement: We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST
  antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for
  kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided
  by Tsutomu Tanabe. 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. 694539 to Ryuichi Shigemoto,
  no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385
  to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard
  Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.
article_number: e68274
article_processing_charge: No
article_type: original
author:
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Diego
  full_name: Fernández-Fernández, Diego
  last_name: Fernández-Fernández
- first_name: Thorsten
  full_name: Fritzius, Thorsten
  last_name: Fritzius
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
- first_name: Jacqueline-Claire
  full_name: Montanaro-Punzengruber, Jacqueline-Claire
  id: 3786AB44-F248-11E8-B48F-1D18A9856A87
  last_name: Montanaro-Punzengruber
- first_name: Martin
  full_name: Gassmann, Martin
  last_name: Gassmann
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Akos
  full_name: Kulik, Akos
  last_name: Kulik
- first_name: Bernhard
  full_name: Bettler, Bernhard
  last_name: Bettler
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
citation:
  ama: Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary
    subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>.
    2021;10. doi:<a href="https://doi.org/10.7554/ELIFE.68274">10.7554/ELIFE.68274</a>
  apa: Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst,
    D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits
    modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/ELIFE.68274">https://doi.org/10.7554/ELIFE.68274</a>
  chicago: Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten
    Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber,
    et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from
    Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a
    href="https://doi.org/10.7554/ELIFE.68274">https://doi.org/10.7554/ELIFE.68274</a>.
  ieee: P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated
    release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences
    Publications, 2021.
  ista: Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D,
    Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B,
    Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate
    Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.
  mla: Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated
    Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife
    Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/ELIFE.68274">10.7554/ELIFE.68274</a>.
  short: P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst,
    H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B.
    Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).
date_created: 2021-05-30T22:01:23Z
date_published: 2021-04-29T00:00:00Z
date_updated: 2024-03-25T23:30:16Z
day: '29'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.7554/ELIFE.68274
ec_funded: 1
external_id:
  isi:
  - '000651761700001'
file:
- access_level: open_access
  checksum: 6ebcb79999f889766f7cd79ee134ad28
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-05-31T09:43:09Z
  date_updated: 2021-05-31T09:43:09Z
  file_id: '9440'
  file_name: 2021_eLife_Bhandari.pdf
  file_size: 8174719
  relation: main_file
  success: 1
file_date_updated: 2021-05-31T09:43:09Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '04'
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: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - relation: earlier_version
    url: https://doi.org/10.1101/2020.04.16.045112
  record:
  - id: '9562'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial
  habenula terminals
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: 10
year: '2021'
...
---
_id: '10116'
abstract:
- lang: eng
  text: The ubiquitous Ca2+ sensor calmodulin (CaM) binds and regulates many proteins,
    including ion channels, CaM kinases, and calcineurin, according to Ca2+-CaM levels.
    What regulates neuronal CaM levels, is, however, unclear. CaM-binding transcription
    activators (CAMTAs) are ancient proteins expressed broadly in nervous systems
    and whose loss confers pleiotropic behavioral defects in flies, mice, and humans.
    Using Caenorhabditis elegans and Drosophila, we show that CAMTAs control neuronal
    CaM levels. The behavioral and neuronal Ca2+ signaling defects in mutants lacking
    camt-1, the sole C. elegans CAMTA, can be rescued by supplementing neuronal CaM.
    CAMT-1 binds multiple sites in the CaM promoter and deleting these sites phenocopies
    camt-1. Our data suggest CAMTAs mediate a conserved and general mechanism that
    controls neuronal CaM levels, thereby regulating Ca2+ signaling, physiology, and
    behavior.
acknowledgement: The authors thank the MRC-LMB Flow Cytometry facility and Imaging
  Service for support, the Cancer Research UK Cambridge Institute Genomics Core for
  Next Generation Sequencing, Julie Ahringer and Alex Appert for advice and technical
  help for ChIP-seq experiments, Paula Freire-Pritchett, Tim Stevens, and Gurpreet
  Ghattaoraya for RNA-seq and ChIP-seq analyses, Nikos Chronis for the TN-XL plasmid,
  Hong-Sheng Li and Daisuke Yamamoto for generously sending the tes2 and cro mutants,
  Daria Siekhaus for hosting the fly work, Michaela Misova for technical assistance.
  The authors are very grateful to Salihah Ece Sönmez for teaching us how to dissect,
  mount and stain Drosophila retinae. This work was supported by an Advanced ERC grant
  (269058 ACMO) and a Wellcome Investigator Award (209504/Z/17/Z) to MdB, and an IST
  Plus Fellowship to TV-B (Marie Sklodowska-Curie Agreement no 754411).
article_number: e68238
article_processing_charge: No
article_type: original
author:
- first_name: Thanh
  full_name: Vuong-Brender, Thanh
  id: D389312E-10C4-11EA-ABF4-A4B43DDC885E
  last_name: Vuong-Brender
- first_name: Sean
  full_name: Flynn, Sean
  last_name: Flynn
- first_name: Yvonne
  full_name: Vallis, Yvonne
  id: 05A2795C-31B5-11EA-83A7-7DA23DDC885E
  last_name: Vallis
- first_name: Mario
  full_name: De Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: De Bono
  orcid: 0000-0001-8347-0443
citation:
  ama: Vuong-Brender T, Flynn S, Vallis Y, de Bono M. Neuronal calmodulin levels are
    controlled by CAMTA transcription factors. <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/eLife.68238">10.7554/eLife.68238</a>
  apa: Vuong-Brender, T., Flynn, S., Vallis, Y., &#38; de Bono, M. (2021). Neuronal
    calmodulin levels are controlled by CAMTA transcription factors. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.68238">https://doi.org/10.7554/eLife.68238</a>
  chicago: Vuong-Brender, Thanh, Sean Flynn, Yvonne Vallis, and Mario de Bono. “Neuronal
    Calmodulin Levels Are Controlled by CAMTA Transcription Factors.” <i>ELife</i>.
    eLife Sciences Publications, 2021. <a href="https://doi.org/10.7554/eLife.68238">https://doi.org/10.7554/eLife.68238</a>.
  ieee: T. Vuong-Brender, S. Flynn, Y. Vallis, and M. de Bono, “Neuronal calmodulin
    levels are controlled by CAMTA transcription factors,” <i>eLife</i>, vol. 10.
    eLife Sciences Publications, 2021.
  ista: Vuong-Brender T, Flynn S, Vallis Y, de Bono M. 2021. Neuronal calmodulin levels
    are controlled by CAMTA transcription factors. eLife. 10, e68238.
  mla: Vuong-Brender, Thanh, et al. “Neuronal Calmodulin Levels Are Controlled by
    CAMTA Transcription Factors.” <i>ELife</i>, vol. 10, e68238, eLife Sciences Publications,
    2021, doi:<a href="https://doi.org/10.7554/eLife.68238">10.7554/eLife.68238</a>.
  short: T. Vuong-Brender, S. Flynn, Y. Vallis, M. de Bono, ELife 10 (2021).
date_created: 2021-10-10T22:01:22Z
date_published: 2021-09-17T00:00:00Z
date_updated: 2023-08-14T07:23:39Z
day: '17'
ddc:
- '610'
department:
- _id: MaDe
doi: 10.7554/eLife.68238
ec_funded: 1
external_id:
  isi:
  - '000695716100001'
  pmid:
  - '34499028'
file:
- access_level: open_access
  checksum: b465e172d2b1f57aa26a2571a085d052
  content_type: application/pdf
  creator: cchlebak
  date_created: 2021-10-11T14:15:07Z
  date_updated: 2021-10-11T14:15:07Z
  file_id: '10122'
  file_name: 2021_eLife_VuongBrender.pdf
  file_size: 1774624
  relation: main_file
  success: 1
file_date_updated: 2021-10-11T14:15:07Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neuronal calmodulin levels are controlled by CAMTA transcription factors
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: 10
year: '2021'
...
---
_id: '10403'
abstract:
- lang: eng
  text: Synaptic transmission, connectivity, and dendritic morphology mature in parallel
    during brain development and are often disrupted in neurodevelopmental disorders.
    Yet how these changes influence the neuronal computations necessary for normal
    brain function are not well understood. To identify cellular mechanisms underlying
    the maturation of synaptic integration in interneurons, we combined patch-clamp
    recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional
    reconstruction of SC morphology with excitatory synapse location, and biophysical
    modeling. We found that postnatal maturation of postsynaptic strength was homogeneously
    reduced along the somatodendritic axis, but dendritic integration was always sublinear.
    However, dendritic branching increased without changes in synapse density, leading
    to a substantial gain in distal inputs. Thus, changes in synapse distribution,
    rather than dendrite cable properties, are the dominant mechanism underlying the
    maturation of neuronal computation. These mechanisms favor the emergence of a
    spatially compartmentalized two-stage integration model promoting location-dependent
    integration within dendritic subunits.
acknowledgement: This study was supported by the Centre National de la Recherche Scientifique
  and the Agence Nationale de la Recherche (ANR-13-BSV4-00166, to LC and DAD). TA
  was supported by fellowships from the Fondation pour la Recherche Medicale and the
  Swedish Research Council. We thank Dmitry Ershov from the Image Analysis Hub of
  the Institut Pasteur, Elodie Le Monnier, Elena Hollergschwandtner, Vanessa Zheden,
  and Corinne Nantet for technical support and Haining Zhong for providing the Venus-tagged
  PSD95 mouse line. We would like to thank Alberto Bacci, Ann Lohof, and Nelson Rebola
  for comments on the manuscript.
article_number: e65954
article_processing_charge: No
article_type: original
author:
- first_name: Celia
  full_name: Biane, Celia
  last_name: Biane
- first_name: Florian
  full_name: Rückerl, Florian
  last_name: Rückerl
- first_name: Therese
  full_name: Abrahamsson, Therese
  last_name: Abrahamsson
- first_name: Cécile
  full_name: Saint-Cloment, Cécile
  last_name: Saint-Cloment
- first_name: Jean
  full_name: Mariani, Jean
  last_name: Mariani
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: David A.
  full_name: Digregorio, David A.
  last_name: Digregorio
- first_name: Rachel M.
  full_name: Sherrard, Rachel M.
  last_name: Sherrard
- first_name: Laurence
  full_name: Cathala, Laurence
  last_name: Cathala
citation:
  ama: Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage
    nonlinear synaptic integration in cerebellar interneurons. <i>eLife</i>. 2021;10.
    doi:<a href="https://doi.org/10.7554/eLife.65954">10.7554/eLife.65954</a>
  apa: Biane, C., Rückerl, F., Abrahamsson, T., Saint-Cloment, C., Mariani, J., Shigemoto,
    R., … Cathala, L. (2021). Developmental emergence of two-stage nonlinear synaptic
    integration in cerebellar interneurons. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.65954">https://doi.org/10.7554/eLife.65954</a>
  chicago: Biane, Celia, Florian Rückerl, Therese Abrahamsson, Cécile Saint-Cloment,
    Jean Mariani, Ryuichi Shigemoto, David A. Digregorio, Rachel M. Sherrard, and
    Laurence Cathala. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration
    in Cerebellar Interneurons.” <i>ELife</i>. eLife Sciences Publications, 2021.
    <a href="https://doi.org/10.7554/eLife.65954">https://doi.org/10.7554/eLife.65954</a>.
  ieee: C. Biane <i>et al.</i>, “Developmental emergence of two-stage nonlinear synaptic
    integration in cerebellar interneurons,” <i>eLife</i>, vol. 10. eLife Sciences
    Publications, 2021.
  ista: Biane C, Rückerl F, Abrahamsson T, Saint-Cloment C, Mariani J, Shigemoto R,
    Digregorio DA, Sherrard RM, Cathala L. 2021. Developmental emergence of two-stage
    nonlinear synaptic integration in cerebellar interneurons. eLife. 10, e65954.
  mla: Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic
    Integration in Cerebellar Interneurons.” <i>ELife</i>, vol. 10, e65954, eLife
    Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/eLife.65954">10.7554/eLife.65954</a>.
  short: C. Biane, F. Rückerl, T. Abrahamsson, C. Saint-Cloment, J. Mariani, R. Shigemoto,
    D.A. Digregorio, R.M. Sherrard, L. Cathala, ELife 10 (2021).
date_created: 2021-12-05T23:01:40Z
date_published: 2021-11-03T00:00:00Z
date_updated: 2023-08-14T13:12:07Z
day: '03'
ddc:
- '570'
department:
- _id: RySh
doi: 10.7554/eLife.65954
external_id:
  isi:
  - '000715789500001'
file:
- access_level: open_access
  checksum: c7c33c3319428d56e332e22349c50ed3
  content_type: application/pdf
  creator: cchlebak
  date_created: 2021-12-10T08:31:41Z
  date_updated: 2021-12-10T08:31:41Z
  file_id: '10528'
  file_name: 2021_eLife_Biane.pdf
  file_size: 13131322
  relation: main_file
  success: 1
file_date_updated: 2021-12-10T08:31:41Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Developmental emergence of two-stage nonlinear synaptic integration in cerebellar
  interneurons
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: 10
year: '2021'
...
---
_id: '10606'
abstract:
- lang: eng
  text: Cell division orientation is thought to result from a competition between
    cell geometry and polarity domains controlling the position of the mitotic spindle
    during mitosis. Depending on the level of cell shape anisotropy or the strength
    of the polarity domain, one dominates the other and determines the orientation
    of the spindle. Whether and how such competition is also at work to determine
    unequal cell division (UCD), producing daughter cells of different size, remains
    unclear. Here, we show that cell geometry and polarity domains cooperate, rather
    than compete, in positioning the cleavage plane during UCDs in early ascidian
    embryos. We found that the UCDs and their orientation at the ascidian third cleavage
    rely on the spindle tilting in an anisotropic cell shape, and cortical polarity
    domains exerting different effects on spindle astral microtubules. By systematically
    varying mitotic cell shape, we could modulate the effect of attractive and repulsive
    polarity domains and consequently generate predicted daughter cell size asymmetries
    and position. We therefore propose that the spindle position during UCD is set
    by the combined activities of cell geometry and polarity domains, where cell geometry
    modulates the effect of cortical polarity domain(s).
acknowledged_ssus:
- _id: NanoFab
- _id: Bio
acknowledgement: 'We thank members of the Heisenberg and McDougall groups for technical
  advice and discussion. We are grateful to the Bioimaging and Nanofabrication facilities
  of IST Austria and the Imaging Platform (PIM) and animal facility (CRB) of Institut
  de la Mer de Villefranche (IMEV), which is supported by EMBRC-France, whose French
  state funds are managed by the ANR within the Investments of the Future program
  under reference ANR-10-INBS-0, for continuous support. This work was supported by
  a collaborative grant from the French Government funding agency Agence National
  de la Recherche to McDougall (ANR ''MorCell'': ANR-17-CE 13-0028) and the Austrian
  Science Fund to Heisenberg (FWF: I 3601-B27).'
article_number: e75639
article_processing_charge: No
article_type: original
author:
- first_name: Benoit G
  full_name: Godard, Benoit G
  id: 33280250-F248-11E8-B48F-1D18A9856A87
  last_name: Godard
- first_name: Remi
  full_name: Dumollard, Remi
  last_name: Dumollard
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
- first_name: Alex
  full_name: Mcdougall, Alex
  last_name: Mcdougall
citation:
  ama: Godard BG, Dumollard R, Heisenberg C-PJ, Mcdougall A. Combined effect of cell
    geometry and polarity domains determines the orientation of unequal division.
    <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/eLife.75639">10.7554/eLife.75639</a>
  apa: Godard, B. G., Dumollard, R., Heisenberg, C.-P. J., &#38; Mcdougall, A. (2021).
    Combined effect of cell geometry and polarity domains determines the orientation
    of unequal division. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.75639">https://doi.org/10.7554/eLife.75639</a>
  chicago: Godard, Benoit G, Remi Dumollard, Carl-Philipp J Heisenberg, and Alex Mcdougall.
    “Combined Effect of Cell Geometry and Polarity Domains Determines the Orientation
    of Unequal Division.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href="https://doi.org/10.7554/eLife.75639">https://doi.org/10.7554/eLife.75639</a>.
  ieee: B. G. Godard, R. Dumollard, C.-P. J. Heisenberg, and A. Mcdougall, “Combined
    effect of cell geometry and polarity domains determines the orientation of unequal
    division,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.
  ista: Godard BG, Dumollard R, Heisenberg C-PJ, Mcdougall A. 2021. Combined effect
    of cell geometry and polarity domains determines the orientation of unequal division.
    eLife. 10, e75639.
  mla: Godard, Benoit G., et al. “Combined Effect of Cell Geometry and Polarity Domains
    Determines the Orientation of Unequal Division.” <i>ELife</i>, vol. 10, e75639,
    eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/eLife.75639">10.7554/eLife.75639</a>.
  short: B.G. Godard, R. Dumollard, C.-P.J. Heisenberg, A. Mcdougall, ELife 10 (2021).
date_created: 2022-01-09T23:01:26Z
date_published: 2021-12-21T00:00:00Z
date_updated: 2023-08-17T06:32:44Z
day: '21'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.7554/eLife.75639
external_id:
  isi:
  - '000733610100001'
file:
- access_level: open_access
  checksum: 759c7a873d554c48a6639e6350746ca6
  content_type: application/pdf
  creator: alisjak
  date_created: 2022-01-10T09:40:37Z
  date_updated: 2022-01-10T09:40:37Z
  file_id: '10611'
  file_name: 2021_eLife_Godard.pdf
  file_size: 7769934
  relation: main_file
  success: 1
file_date_updated: 2022-01-10T09:40:37Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 2646861A-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03601
  name: Control of embryonic cleavage pattern
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Combined effect of cell geometry and polarity domains determines the orientation
  of unequal division
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: 10
year: '2021'
...
---
_id: '9746'
abstract:
- lang: eng
  text: Evolutionary adaptation is a major source of antibiotic resistance in bacterial
    pathogens. Evolution-informed therapy aims to constrain resistance by accounting
    for bacterial evolvability. Sequential treatments with antibiotics that target
    different bacterial processes were previously shown to limit adaptation through
    genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous
    sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly
    lead to cross-resistance. We here challenged this assumption by determining the
    evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments
    involving both heterogenous and homogeneous antibiotic sets. To our surprise,
    we found that fast switching between only β-lactam antibiotics resulted in increased
    extinction of bacterial populations. We demonstrate that extinction is favored
    by low rates of spontaneous resistance emergence and low levels of spontaneous
    cross-resistance among the antibiotics in sequence. The uncovered principles may
    help to guide the optimized use of available antibiotics in highly potent, evolution-informed
    treatment designs.
acknowledgement: We would like to thank Leif Tueffers and João Botelho for discussions
  and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge
  financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS,
  and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the
  Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS
  scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus
  Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further
  supported by the German Science Foundation Research Infrastructure NGS_CC (project
  407495230) as part of the Next Generation Sequencing Competence Network (project
  423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis
  Kiel (CCGA Kiel).
article_number: e68876
article_processing_charge: No
article_type: original
author:
- first_name: Aditi
  full_name: Batra, Aditi
  last_name: Batra
- first_name: Roderich
  full_name: Römhild, Roderich
  id: 68E56E44-62B0-11EA-B963-444F3DDC885E
  last_name: Römhild
  orcid: 0000-0001-9480-5261
- first_name: Emilie
  full_name: Rousseau, Emilie
  last_name: Rousseau
- first_name: Sören
  full_name: Franzenburg, Sören
  last_name: Franzenburg
- first_name: Stefan
  full_name: Niemann, Stefan
  last_name: Niemann
- first_name: Hinrich
  full_name: Schulenburg, Hinrich
  last_name: Schulenburg
citation:
  ama: Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High
    potency of sequential therapy with only beta-lactam antibiotics. <i>eLife</i>.
    2021;10. doi:<a href="https://doi.org/10.7554/elife.68876">10.7554/elife.68876</a>
  apa: Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., &#38; Schulenburg,
    H. (2021). High potency of sequential therapy with only beta-lactam antibiotics.
    <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.68876">https://doi.org/10.7554/elife.68876</a>
  chicago: Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan
    Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only
    Beta-Lactam Antibiotics.” <i>ELife</i>. eLife Sciences Publications, 2021. <a
    href="https://doi.org/10.7554/elife.68876">https://doi.org/10.7554/elife.68876</a>.
  ieee: A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg,
    “High potency of sequential therapy with only beta-lactam antibiotics,” <i>eLife</i>,
    vol. 10. eLife Sciences Publications, 2021.
  ista: Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021.
    High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10,
    e68876.
  mla: Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam
    Antibiotics.” <i>ELife</i>, vol. 10, e68876, eLife Sciences Publications, 2021,
    doi:<a href="https://doi.org/10.7554/elife.68876">10.7554/elife.68876</a>.
  short: A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg,
    ELife 10 (2021).
date_created: 2021-07-28T13:36:57Z
date_published: 2021-07-28T00:00:00Z
date_updated: 2023-08-11T10:26:29Z
day: '28'
department:
- _id: CaGu
doi: 10.7554/elife.68876
external_id:
  isi:
  - '000692027800001'
  pmid:
  - '34318749'
intvolume: '        10'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.7554/eLife.68876
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: High potency of sequential therapy with only beta-lactam antibiotics
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '9999'
abstract:
- lang: eng
  text: 'The developmental strategies used by progenitor cells to endure a safe journey
    from their induction place towards the site of terminal differentiation are still
    poorly understood. Here we uncovered a progenitor cell allocation mechanism that
    stems from an incomplete process of epithelial delamination that allows progenitors
    to coordinate their movement with adjacent extra-embryonic tissues. Progenitors
    of the zebrafish laterality organ originate from the surface epithelial enveloping
    layer by an apical constriction process of cell delamination. During this process,
    progenitors retain long-term apical contacts that enable the epithelial layer
    to pull a subset of progenitors along their way towards the vegetal pole. The
    remaining delaminated progenitors follow apically-attached progenitors’ movement
    by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm,
    ensuring their fate and collective allocation at the differentiation site. Thus,
    we reveal that incomplete delamination serves as a cellular platform for coordinated
    tissue movements during development. Impact Statement: Incomplete delamination
    serves as a cellular platform for coordinated tissue movements during development,
    guiding newly formed progenitor cell groups to the differentiation site.'
article_number: e66483
article_processing_charge: Yes
article_type: original
author:
- first_name: Eduardo
  full_name: Pulgar, Eduardo
  last_name: Pulgar
- first_name: Cornelia
  full_name: Schwayer, Cornelia
  id: 3436488C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwayer
  orcid: 0000-0001-5130-2226
- first_name: Néstor
  full_name: Guerrero, Néstor
  last_name: Guerrero
- first_name: Loreto
  full_name: López, Loreto
  last_name: López
- first_name: Susana
  full_name: Márquez, Susana
  last_name: Márquez
- first_name: Steffen
  full_name: Härtel, Steffen
  last_name: Härtel
- first_name: Rodrigo
  full_name: Soto, Rodrigo
  last_name: Soto
- first_name: Carl Philipp
  full_name: Heisenberg, Carl Philipp
  last_name: Heisenberg
- first_name: Miguel L.
  full_name: Concha, Miguel L.
  last_name: Concha
citation:
  ama: Pulgar E, Schwayer C, Guerrero N, et al. Apical contacts stemming from incomplete
    delamination guide progenitor cell allocation through a dragging mechanism. <i>eLife</i>.
    2021;10. doi:<a href="https://doi.org/10.7554/eLife.66483">10.7554/eLife.66483</a>
  apa: Pulgar, E., Schwayer, C., Guerrero, N., López, L., Márquez, S., Härtel, S.,
    … Concha, M. L. (2021). Apical contacts stemming from incomplete delamination
    guide progenitor cell allocation through a dragging mechanism. <i>ELife</i>. eLife
    Sciences Publications. <a href="https://doi.org/10.7554/eLife.66483">https://doi.org/10.7554/eLife.66483</a>
  chicago: Pulgar, Eduardo, Cornelia Schwayer, Néstor Guerrero, Loreto López, Susana
    Márquez, Steffen Härtel, Rodrigo Soto, Carl Philipp Heisenberg, and Miguel L.
    Concha. “Apical Contacts Stemming from Incomplete Delamination Guide Progenitor
    Cell Allocation through a Dragging Mechanism.” <i>ELife</i>. eLife Sciences Publications,
    2021. <a href="https://doi.org/10.7554/eLife.66483">https://doi.org/10.7554/eLife.66483</a>.
  ieee: E. Pulgar <i>et al.</i>, “Apical contacts stemming from incomplete delamination
    guide progenitor cell allocation through a dragging mechanism,” <i>eLife</i>,
    vol. 10. eLife Sciences Publications, 2021.
  ista: Pulgar E, Schwayer C, Guerrero N, López L, Márquez S, Härtel S, Soto R, Heisenberg
    CP, Concha ML. 2021. Apical contacts stemming from incomplete delamination guide
    progenitor cell allocation through a dragging mechanism. eLife. 10, e66483.
  mla: Pulgar, Eduardo, et al. “Apical Contacts Stemming from Incomplete Delamination
    Guide Progenitor Cell Allocation through a Dragging Mechanism.” <i>ELife</i>,
    vol. 10, e66483, eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/eLife.66483">10.7554/eLife.66483</a>.
  short: E. Pulgar, C. Schwayer, N. Guerrero, L. López, S. Márquez, S. Härtel, R.
    Soto, C.P. Heisenberg, M.L. Concha, ELife 10 (2021).
date_created: 2021-09-12T22:01:23Z
date_published: 2021-08-27T00:00:00Z
date_updated: 2023-08-14T06:53:33Z
day: '27'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.7554/eLife.66483
ec_funded: 1
external_id:
  isi:
  - '000700428500001'
  pmid:
  - '34448451'
file:
- access_level: open_access
  checksum: a3f82b0499cc822ac1eab48a01f3f57e
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-13T08:03:37Z
  date_updated: 2022-05-13T08:03:37Z
  file_id: '11371'
  file_name: 2021_eLife_Pulgar.pdf
  file_size: 9010446
  relation: main_file
  success: 1
file_date_updated: 2022-05-13T08:03:37Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
keyword:
- cell delamination
- apical constriction
- dragging
- mechanical forces
- collective 18 locomotion
- dorsal forerunner cells
- zebrafish
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Apical contacts stemming from incomplete delamination guide progenitor cell
  allocation through a dragging mechanism
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: 10
year: '2021'
...
---
_id: '8127'
abstract:
- lang: eng
  text: Mechanistic modeling in neuroscience aims to explain observed phenomena in
    terms of underlying causes. However, determining which model parameters agree
    with complex and stochastic neural data presents a significant challenge. We address
    this challenge with a machine learning tool which uses deep neural density estimators—trained
    using model simulations—to carry out Bayesian inference and retrieve the full
    space of parameters compatible with raw data or selected data features. Our method
    is scalable in parameters and data features and can rapidly analyze new data after
    initial training. We demonstrate the power and flexibility of our approach on
    receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize
    the space of circuit configurations giving rise to rhythmic activity in the crustacean
    stomatogastric ganglion, and use these results to derive hypotheses for underlying
    compensation mechanisms. Our approach will help close the gap between data-driven
    and theory-driven models of neural dynamics.
acknowledgement: We thank Mahmood S Hoseini and Michael Stryker for sharing their
  data for Figure 2, and Philipp Berens, Sean Bittner, Jan Boelts, John Cunningham,
  Richard Gao, Scott Linderman, Eve Marder, Iain Murray, George Papamakarios, Astrid
  Prinz, Auguste Schulz and Srinivas Turaga for discussions and/or comments on the
  manuscript. This work was supported by the German Research Foundation (DFG) through
  SFB 1233 ‘Robust Vision’, (276693517), SFB 1089 ‘Synaptic Microcircuits’, SPP 2041
  ‘Computational Connectomics’ and Germany's Excellence Strategy – EXC-Number 2064/1
  – Project number 390727645 and the German Federal Ministry of Education and Research
  (BMBF, project ‘ADIMEM’, FKZ 01IS18052 A-D) to JHM, a Sir Henry Dale Fellowship
  by the Wellcome Trust and the Royal Society (WT100000; WFP and TPV), a Wellcome
  Trust Senior Research Fellowship (214316/Z/18/Z; TPV), a ERC Consolidator Grant
  (SYNAPSEEK; WPF and CC), and a UK Research and Innovation, Biotechnology and Biological
  Sciences Research Council (CC, UKRI-BBSRC BB/N019512/1). We gratefully acknowledge
  the Leibniz Supercomputing Centre for funding this project by providing computing
  time on its Linux-Cluster.
article_number: e56261
article_processing_charge: No
article_type: original
author:
- first_name: Pedro J.
  full_name: Gonçalves, Pedro J.
  last_name: Gonçalves
  orcid: 0000-0002-6987-4836
- first_name: Jan-Matthis
  full_name: Lueckmann, Jan-Matthis
  last_name: Lueckmann
  orcid: 0000-0003-4320-4663
- first_name: Michael
  full_name: Deistler, Michael
  last_name: Deistler
  orcid: 0000-0002-3573-0404
- first_name: Marcel
  full_name: Nonnenmacher, Marcel
  last_name: Nonnenmacher
  orcid: 0000-0001-6044-6627
- first_name: Kaan
  full_name: Öcal, Kaan
  last_name: Öcal
  orcid: 0000-0002-8528-6858
- first_name: Giacomo
  full_name: Bassetto, Giacomo
  last_name: Bassetto
- first_name: Chaitanya
  full_name: Chintaluri, Chaitanya
  id: BA06AFEE-A4BA-11EA-AE5C-14673DDC885E
  last_name: Chintaluri
  orcid: 0000-0003-4252-1608
- first_name: William F.
  full_name: Podlaski, William F.
  last_name: Podlaski
  orcid: 0000-0001-6619-7502
- first_name: Sara A.
  full_name: Haddad, Sara A.
  last_name: Haddad
  orcid: 0000-0003-0807-0823
- first_name: Tim P
  full_name: Vogels, Tim P
  id: CB6FF8D2-008F-11EA-8E08-2637E6697425
  last_name: Vogels
  orcid: 0000-0003-3295-6181
- first_name: David S.
  full_name: Greenberg, David S.
  last_name: Greenberg
- first_name: Jakob H.
  full_name: Macke, Jakob H.
  last_name: Macke
  orcid: 0000-0001-5154-8912
citation:
  ama: Gonçalves PJ, Lueckmann J-M, Deistler M, et al. Training deep neural density
    estimators to identify mechanistic models of neural dynamics. <i>eLife</i>. 2020;9.
    doi:<a href="https://doi.org/10.7554/eLife.56261">10.7554/eLife.56261</a>
  apa: Gonçalves, P. J., Lueckmann, J.-M., Deistler, M., Nonnenmacher, M., Öcal, K.,
    Bassetto, G., … Macke, J. H. (2020). Training deep neural density estimators to
    identify mechanistic models of neural dynamics. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.56261">https://doi.org/10.7554/eLife.56261</a>
  chicago: Gonçalves, Pedro J., Jan-Matthis Lueckmann, Michael Deistler, Marcel Nonnenmacher,
    Kaan Öcal, Giacomo Bassetto, Chaitanya Chintaluri, et al. “Training Deep Neural
    Density Estimators to Identify Mechanistic Models of Neural Dynamics.” <i>ELife</i>.
    eLife Sciences Publications, 2020. <a href="https://doi.org/10.7554/eLife.56261">https://doi.org/10.7554/eLife.56261</a>.
  ieee: P. J. Gonçalves <i>et al.</i>, “Training deep neural density estimators to
    identify mechanistic models of neural dynamics,” <i>eLife</i>, vol. 9. eLife Sciences
    Publications, 2020.
  ista: Gonçalves PJ, Lueckmann J-M, Deistler M, Nonnenmacher M, Öcal K, Bassetto
    G, Chintaluri C, Podlaski WF, Haddad SA, Vogels TP, Greenberg DS, Macke JH. 2020.
    Training deep neural density estimators to identify mechanistic models of neural
    dynamics. eLife. 9, e56261.
  mla: Gonçalves, Pedro J., et al. “Training Deep Neural Density Estimators to Identify
    Mechanistic Models of Neural Dynamics.” <i>ELife</i>, vol. 9, e56261, eLife Sciences
    Publications, 2020, doi:<a href="https://doi.org/10.7554/eLife.56261">10.7554/eLife.56261</a>.
  short: P.J. Gonçalves, J.-M. Lueckmann, M. Deistler, M. Nonnenmacher, K. Öcal, G.
    Bassetto, C. Chintaluri, W.F. Podlaski, S.A. Haddad, T.P. Vogels, D.S. Greenberg,
    J.H. Macke, ELife 9 (2020).
date_created: 2020-07-16T12:26:04Z
date_published: 2020-09-17T00:00:00Z
date_updated: 2023-08-22T07:54:52Z
day: '17'
ddc:
- '570'
department:
- _id: TiVo
doi: 10.7554/eLife.56261
ec_funded: 1
external_id:
  isi:
  - '000584989400001'
  pmid:
  - '32940606'
file:
- access_level: open_access
  checksum: c4300ddcd93ed03fc9c6cdf1f77890be
  content_type: application/pdf
  creator: cziletti
  date_created: 2020-10-27T11:37:32Z
  date_updated: 2020-10-27T11:37:32Z
  file_id: '8709'
  file_name: 2020_eLife_Gonçalves.pdf
  file_size: 17355867
  relation: main_file
  success: 1
file_date_updated: 2020-10-27T11:37:32Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
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.
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Training deep neural density estimators to identify mechanistic models of neural
  dynamics
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: 9
year: '2020'
...
---
_id: '7490'
abstract:
- lang: eng
  text: In plants, clathrin mediated endocytosis (CME) represents the major route
    for cargo internalisation from the cell surface. It has been assumed to operate
    in an evolutionary conserved manner as in yeast and animals. Here we report characterisation
    of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement
    in electron microscopy and quantitative live imaging techniques. Arabidopsis CME
    appears to follow the constant curvature model and the bona fide CME population
    generates vesicles of a predominantly hexagonal-basket type; larger and with faster
    kinetics than in other models. Contrary to the existing paradigm, actin is dispensable
    for CME events at the plasma membrane but plays a unique role in collecting endocytic
    vesicles, sorting of internalised cargos and directional endosome movement that
    itself actively promote CME events. Internalized vesicles display a strongly delayed
    and sequential uncoating. These unique features highlight the independent evolution
    of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
article_number: e52067
article_processing_charge: No
article_type: original
author:
- first_name: Madhumitha
  full_name: Narasimhan, Madhumitha
  id: 44BF24D0-F248-11E8-B48F-1D18A9856A87
  last_name: Narasimhan
  orcid: 0000-0002-8600-0671
- 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: Roshan
  full_name: Prizak, Roshan
  id: 4456104E-F248-11E8-B48F-1D18A9856A87
  last_name: Prizak
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Shutang
  full_name: Tan, Shutang
  id: 2DE75584-F248-11E8-B48F-1D18A9856A87
  last_name: Tan
  orcid: 0000-0002-0471-8285
- first_name: Barbara E
  full_name: Casillas Perez, Barbara E
  id: 351ED2AA-F248-11E8-B48F-1D18A9856A87
  last_name: Casillas Perez
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic
    framework of clathrin-mediated endocytosis in plants. <i>eLife</i>. 2020;9. doi:<a
    href="https://doi.org/10.7554/eLife.52067">10.7554/eLife.52067</a>
  apa: Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas
    Perez, B. E., &#38; Friml, J. (2020). Evolutionarily unique mechanistic framework
    of clathrin-mediated endocytosis in plants. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.52067">https://doi.org/10.7554/eLife.52067</a>
  chicago: Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann,
    Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique
    Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>.
    eLife Sciences Publications, 2020. <a href="https://doi.org/10.7554/eLife.52067">https://doi.org/10.7554/eLife.52067</a>.
  ieee: M. Narasimhan <i>et al.</i>, “Evolutionarily unique mechanistic framework
    of clathrin-mediated endocytosis in plants,” <i>eLife</i>, vol. 9. eLife Sciences
    Publications, 2020.
  ista: Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE,
    Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated
    endocytosis in plants. eLife. 9, e52067.
  mla: Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework
    of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>, vol. 9, e52067, eLife
    Sciences Publications, 2020, doi:<a href="https://doi.org/10.7554/eLife.52067">10.7554/eLife.52067</a>.
  short: M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas
    Perez, J. Friml, ELife 9 (2020).
date_created: 2020-02-16T23:00:50Z
date_published: 2020-01-23T00:00:00Z
date_updated: 2023-08-18T06:33:07Z
day: '23'
ddc:
- '570'
- '580'
department:
- _id: JiFr
- _id: GaTk
- _id: EM-Fac
- _id: SyCr
doi: 10.7554/eLife.52067
ec_funded: 1
external_id:
  isi:
  - '000514104100001'
  pmid:
  - '31971511'
file:
- access_level: open_access
  checksum: 2052daa4be5019534f3a42f200a09f32
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-18T07:21:16Z
  date_updated: 2020-07-14T12:47:59Z
  file_id: '7494'
  file_name: 2020_eLife_Narasimhan.pdf
  file_size: 7247468
  relation: main_file
file_date_updated: 2020-07-14T12:47:59Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 26538374-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03630
  name: Molecular mechanisms of endocytic cargo recognition in plants
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis
  in plants
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: 9
year: '2020'
...
---
_id: '9445'
abstract:
- lang: eng
  text: Cytosine methylation regulates essential genome functions across eukaryotes,
    but the fundamental question of whether nucleosomal or naked DNA is the preferred
    substrate of plant and animal methyltransferases remains unresolved. Here, we
    show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler
    biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana
    and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome,
    suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases
    in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone
    H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of
    species that diverged from flowering plants and animals over a billion years ago.
    Our results indicate that in the absence of remodeling, nucleosomes are strong
    barriers to DNA methyltransferases. Linker-specific methylation can evolve simply
    by breaking the connection between nucleosome remodeling and DNA methylation.
article_number: e30674
article_processing_charge: No
article_type: original
author:
- first_name: David B
  full_name: Lyons, David B
  last_name: Lyons
- first_name: Daniel
  full_name: Zilberman, Daniel
  id: 6973db13-dd5f-11ea-814e-b3e5455e9ed1
  last_name: Zilberman
  orcid: 0000-0002-0123-8649
citation:
  ama: Lyons DB, Zilberman D. DDM1 and Lsh remodelers allow methylation of DNA wrapped
    in nucleosomes. <i>eLife</i>. 2017;6. doi:<a href="https://doi.org/10.7554/elife.30674">10.7554/elife.30674</a>
  apa: Lyons, D. B., &#38; Zilberman, D. (2017). DDM1 and Lsh remodelers allow methylation
    of DNA wrapped in nucleosomes. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.30674">https://doi.org/10.7554/elife.30674</a>
  chicago: Lyons, David B, and Daniel Zilberman. “DDM1 and Lsh Remodelers Allow Methylation
    of DNA Wrapped in Nucleosomes.” <i>ELife</i>. eLife Sciences Publications, 2017.
    <a href="https://doi.org/10.7554/elife.30674">https://doi.org/10.7554/elife.30674</a>.
  ieee: D. B. Lyons and D. Zilberman, “DDM1 and Lsh remodelers allow methylation of
    DNA wrapped in nucleosomes,” <i>eLife</i>, vol. 6. eLife Sciences Publications,
    2017.
  ista: Lyons DB, Zilberman D. 2017. DDM1 and Lsh remodelers allow methylation of
    DNA wrapped in nucleosomes. eLife. 6, e30674.
  mla: Lyons, David B., and Daniel Zilberman. “DDM1 and Lsh Remodelers Allow Methylation
    of DNA Wrapped in Nucleosomes.” <i>ELife</i>, vol. 6, e30674, eLife Sciences Publications,
    2017, doi:<a href="https://doi.org/10.7554/elife.30674">10.7554/elife.30674</a>.
  short: D.B. Lyons, D. Zilberman, ELife 6 (2017).
date_created: 2021-06-02T14:28:58Z
date_published: 2017-11-15T00:00:00Z
date_updated: 2021-12-14T07:54:36Z
day: '15'
ddc:
- '570'
department:
- _id: DaZi
doi: 10.7554/elife.30674
extern: '1'
external_id:
  pmid:
  - '29140247'
file:
- access_level: open_access
  checksum: 4cfcdd67511ae4aed3d993550e46e146
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-06-02T14:33:36Z
  date_updated: 2021-06-02T14:33:36Z
  file_id: '9446'
  file_name: 2017_eLife_Lyons.pdf
  file_size: 1603102
  relation: main_file
  success: 1
file_date_updated: 2021-06-02T14:33:36Z
has_accepted_license: '1'
intvolume: '         6'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
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: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 6
year: '2017'
...
