---
_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. eLife. 2020;9. doi:10.7554/eLife.52067
apa: Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas
Perez, B. E., & Friml, J. (2020). Evolutionarily unique mechanistic framework
of clathrin-mediated endocytosis in plants. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.52067
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.” ELife.
eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.52067.
ieee: M. Narasimhan et al., “Evolutionarily unique mechanistic framework
of clathrin-mediated endocytosis in plants,” eLife, 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.” ELife, vol. 9, e52067, eLife
Sciences Publications, 2020, doi:10.7554/eLife.52067.
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: '9779'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Distribution of crosstalk values. 2020. doi:10.1371/journal.pcbi.1007642.s003
apa: Grah, R., & Friedlander, T. (2020). Distribution of crosstalk values. Public
Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s003
chicago: Grah, Rok, and Tamar Friedlander. “Distribution of Crosstalk Values.” Public
Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s003.
ieee: R. Grah and T. Friedlander, “Distribution of crosstalk values.” Public Library
of Science, 2020.
ista: Grah R, Friedlander T. 2020. Distribution of crosstalk values, Public Library
of Science, 10.1371/journal.pcbi.1007642.s003.
mla: Grah, Rok, and Tamar Friedlander. Distribution of Crosstalk Values.
Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s003.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:24:37Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-08-18T06:47:47Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s003
month: '02'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: research_data
status: public
status: public
title: Distribution of crosstalk values
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '9776'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Supporting information. 2020. doi:10.1371/journal.pcbi.1007642.s001
apa: Grah, R., & Friedlander, T. (2020). Supporting information. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642.s001
chicago: Grah, Rok, and Tamar Friedlander. “Supporting Information.” Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s001.
ieee: R. Grah and T. Friedlander, “Supporting information.” Public Library of Science,
2020.
ista: Grah R, Friedlander T. 2020. Supporting information, Public Library of Science,
10.1371/journal.pcbi.1007642.s001.
mla: Grah, Rok, and Tamar Friedlander. Supporting Information. Public Library
of Science, 2020, doi:10.1371/journal.pcbi.1007642.s001.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:15:04Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-08-18T06:47:47Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s001
month: '02'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: used_in_publication
status: public
status: public
title: Supporting information
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '7656'
abstract:
- lang: eng
text: 'We propose that correlations among neurons are generically strong enough
to organize neural activity patterns into a discrete set of clusters, which can
each be viewed as a population codeword. Our reasoning starts with the analysis
of retinal ganglion cell data using maximum entropy models, showing that the population
is robustly in a frustrated, marginally sub-critical, or glassy, state. This leads
to an argument that neural populations in many other brain areas might share this
structure. Next, we use latent variable models to show that this glassy state
possesses well-defined clusters of neural activity. Clusters have three appealing
properties: (i) clusters exhibit error correction, i.e., they are reproducibly
elicited by the same stimulus despite variability at the level of constituent
neurons; (ii) clusters encode qualitatively different visual features than their
constituent neurons; and (iii) clusters can be learned by downstream neural circuits
in an unsupervised fashion. We hypothesize that these properties give rise to
a “learnable” neural code which the cortical hierarchy uses to extract increasingly
complex features without supervision or reinforcement.'
article_number: '20'
article_processing_charge: No
article_type: original
author:
- first_name: Michael J.
full_name: Berry, Michael J.
last_name: Berry
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: 'Berry MJ, Tkačik G. Clustering of neural activity: A design principle for
population codes. Frontiers in Computational Neuroscience. 2020;14. doi:10.3389/fncom.2020.00020'
apa: 'Berry, M. J., & Tkačik, G. (2020). Clustering of neural activity: A design
principle for population codes. Frontiers in Computational Neuroscience.
Frontiers. https://doi.org/10.3389/fncom.2020.00020'
chicago: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity:
A Design Principle for Population Codes.” Frontiers in Computational Neuroscience.
Frontiers, 2020. https://doi.org/10.3389/fncom.2020.00020.'
ieee: 'M. J. Berry and G. Tkačik, “Clustering of neural activity: A design principle
for population codes,” Frontiers in Computational Neuroscience, vol. 14.
Frontiers, 2020.'
ista: 'Berry MJ, Tkačik G. 2020. Clustering of neural activity: A design principle
for population codes. Frontiers in Computational Neuroscience. 14, 20.'
mla: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design
Principle for Population Codes.” Frontiers in Computational Neuroscience,
vol. 14, 20, Frontiers, 2020, doi:10.3389/fncom.2020.00020.'
short: M.J. Berry, G. Tkačik, Frontiers in Computational Neuroscience 14 (2020).
date_created: 2020-04-12T22:00:40Z
date_published: 2020-03-13T00:00:00Z
date_updated: 2023-08-18T10:30:11Z
day: '13'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.3389/fncom.2020.00020
external_id:
isi:
- '000525543200001'
pmid:
- '32231528'
file:
- access_level: open_access
checksum: 2b1da23823eae9cedbb42d701945b61e
content_type: application/pdf
creator: dernst
date_created: 2020-04-14T12:20:39Z
date_updated: 2020-07-14T12:48:01Z
file_id: '7659'
file_name: 2020_Frontiers_Berry.pdf
file_size: 4082937
relation: main_file
file_date_updated: 2020-07-14T12:48:01Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Computational Neuroscience
publication_identifier:
eissn:
- '16625188'
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Clustering of neural activity: A design principle for population codes'
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: 14
year: '2020'
...
---
_id: '8698'
abstract:
- lang: eng
text: The brain represents and reasons probabilistically about complex stimuli and
motor actions using a noisy, spike-based neural code. A key building block for
such neural computations, as well as the basis for supervised and unsupervised
learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional
neural activity patterns. Despite progress in statistical modeling of neural responses
and deep learning, current approaches either do not scale to large neural populations
or cannot be implemented using biologically realistic mechanisms. Inspired by
the sparse and random connectivity of real neuronal circuits, we present a model
for neural codes that accurately estimates the likelihood of individual spiking
patterns and has a straightforward, scalable, efficient, learnable, and realistic
neural implementation. This model’s performance on simultaneously recorded spiking
activity of >100 neurons in the monkey visual and prefrontal cortices is comparable
with or better than that of state-of-the-art models. Importantly, the model can
be learned using a small number of samples and using a local learning rule that
utilizes noise intrinsic to neural circuits. Slower, structural changes in random
connectivity, consistent with rewiring and pruning processes, further improve
the efficiency and sparseness of the resulting neural representations. Our results
merge insights from neuroanatomy, machine learning, and theoretical neuroscience
to suggest random sparse connectivity as a key design principle for neuronal computation.
acknowledgement: We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir
Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn
for invaluable discussions of the learning rule. This work was supported by European
Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12
(to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs.
Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to
R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration
on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative
Research in Computational Neuroscience) grant (to R.K. and E.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Ori
full_name: Maoz, Ori
last_name: Maoz
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mohamad Saleh
full_name: Esteki, Mohamad Saleh
last_name: Esteki
- first_name: Roozbeh
full_name: Kiani, Roozbeh
last_name: Kiani
- first_name: Elad
full_name: Schneidman, Elad
last_name: Schneidman
citation:
ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the
National Academy of Sciences of the United States of America. 2020;117(40):25066-25073.
doi:10.1073/pnas.1912804117
apa: Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., & Schneidman, E. (2020).
Learning probabilistic neural representations with randomly connected circuits.
Proceedings of the National Academy of Sciences of the United States of America.
National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117
chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad
Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected
Circuits.” Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117.
ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic
neural representations with randomly connected circuits,” Proceedings of the
National Academy of Sciences of the United States of America, vol. 117, no.
40. National Academy of Sciences, pp. 25066–25073, 2020.
ista: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the National
Academy of Sciences of the United States of America. 117(40), 25066–25073.
mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly
Connected Circuits.” Proceedings of the National Academy of Sciences of the
United States of America, vol. 117, no. 40, National Academy of Sciences,
2020, pp. 25066–73, doi:10.1073/pnas.1912804117.
short: O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of
the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.
date_created: 2020-10-25T23:01:16Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:23Z
day: '06'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.1912804117
external_id:
isi:
- '000579045200012'
pmid:
- '32948691'
file:
- access_level: open_access
checksum: c6a24fdecf3f28faf447078e7a274a88
content_type: application/pdf
creator: cziletti
date_created: 2020-10-27T14:57:50Z
date_updated: 2020-10-27T14:57:50Z
file_id: '8713'
file_name: 2020_PNAS_Maoz.pdf
file_size: 1755359
relation: main_file
success: 1
file_date_updated: 2020-10-27T14:57:50Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '40'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 25066-25073
pmid: 1
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Learning probabilistic neural representations with randomly connected circuits
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
---
_id: '8955'
abstract:
- lang: eng
text: Skeletal muscle activity is continuously modulated across physiologic states
to provide coordination, flexibility and responsiveness to body tasks and external
inputs. Despite the central role the muscular system plays in facilitating vital
body functions, the network of brain-muscle interactions required to control hundreds
of muscles and synchronize their activation in relation to distinct physiologic
states has not been investigated. Recent approaches have focused on general associations
between individual brain rhythms and muscle activation during movement tasks.
However, the specific forms of coupling, the functional network of cortico-muscular
coordination, and how network structure and dynamics are modulated by autonomic
regulation across physiologic states remains unknown. To identify and quantify
the cortico-muscular interaction network and uncover basic features of neuro-autonomic
control of muscle function, we investigate the coupling between synchronous bursts
in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing
the concept of time delay stability and a novel network physiology approach, we
find that the brain-muscle network exhibits complex dynamic patterns of communication
involving multiple brain rhythms across cortical locations and different electromyographic
frequency bands. Moreover, our results show that during each physiologic state
the cortico-muscular network is characterized by a specific profile of network
links strength, where particular brain rhythms play role of main mediators of
interaction and control. Further, we discover a hierarchical reorganization in
network structure across physiologic states, with high connectivity and network
link strength during wake, intermediate during REM and light sleep, and low during
deep sleep, a sleep-stage stratification that demonstrates a unique association
between physiologic states and cortico-muscular network structure. The reported
empirical observations are consistent across individual subjects, indicating universal
behavior in network structure and dynamics, and high sensitivity of cortico-muscular
control to changes in autonomic regulation, even at low levels of physical activity
and muscle tone during sleep. Our findings demonstrate previously unrecognized
basic principles of brain-muscle network communication and control, and provide
new perspectives on the regulatory mechanisms of brain dynamics and locomotor
activation, with potential clinical implications for neurodegenerative, movement
and sleep disorders, and for developing efficient treatment strategies.
acknowledgement: We acknowledge support from the W. M. Keck Foundation, National Institutes
of Health (NIH Grant 1R01-HL098437), the US-Israel Binational Science Foundation
(BSF Grant 2012219), and the Office of Naval Research (ONR Grant 000141010078).
FL acknowledges support also from the European Union's Horizon 2020 research and
innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754411.
article_number: '558070'
article_processing_charge: No
article_type: original
author:
- first_name: Rossella
full_name: Rizzo, Rossella
last_name: Rizzo
- first_name: Xiyun
full_name: Zhang, Xiyun
last_name: Zhang
- first_name: Jilin W.J.L.
full_name: Wang, Jilin W.J.L.
last_name: Wang
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Plamen Ch
full_name: Ivanov, Plamen Ch
last_name: Ivanov
citation:
ama: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. Network physiology of cortico–muscular
interactions. Frontiers in Physiology. 2020;11. doi:10.3389/fphys.2020.558070
apa: Rizzo, R., Zhang, X., Wang, J. W. J. L., Lombardi, F., & Ivanov, P. C.
(2020). Network physiology of cortico–muscular interactions. Frontiers in Physiology.
Frontiers. https://doi.org/10.3389/fphys.2020.558070
chicago: Rizzo, Rossella, Xiyun Zhang, Jilin W.J.L. Wang, Fabrizio Lombardi, and
Plamen Ch Ivanov. “Network Physiology of Cortico–Muscular Interactions.” Frontiers
in Physiology. Frontiers, 2020. https://doi.org/10.3389/fphys.2020.558070.
ieee: R. Rizzo, X. Zhang, J. W. J. L. Wang, F. Lombardi, and P. C. Ivanov, “Network
physiology of cortico–muscular interactions,” Frontiers in Physiology,
vol. 11. Frontiers, 2020.
ista: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. 2020. Network physiology
of cortico–muscular interactions. Frontiers in Physiology. 11, 558070.
mla: Rizzo, Rossella, et al. “Network Physiology of Cortico–Muscular Interactions.”
Frontiers in Physiology, vol. 11, 558070, Frontiers, 2020, doi:10.3389/fphys.2020.558070.
short: R. Rizzo, X. Zhang, J.W.J.L. Wang, F. Lombardi, P.C. Ivanov, Frontiers in
Physiology 11 (2020).
date_created: 2020-12-20T23:01:18Z
date_published: 2020-11-26T00:00:00Z
date_updated: 2023-08-24T11:00:45Z
day: '26'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.3389/fphys.2020.558070
ec_funded: 1
external_id:
isi:
- '000596849400001'
pmid:
- '33324233'
file:
- access_level: open_access
checksum: ef9515b28c5619b7126c0f347958bcb3
content_type: application/pdf
creator: dernst
date_created: 2020-12-21T10:37:50Z
date_updated: 2020-12-21T10:37:50Z
file_id: '8961'
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call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Frontiers in Physiology
publication_identifier:
eissn:
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publication_status: published
publisher: Frontiers
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title: Network physiology of cortico–muscular interactions
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legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
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user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '9000'
abstract:
- lang: eng
text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
quantitative mapping from promoter sequences to gene-expression levels that is
compatible with in vivo and in vitro biophysical measurements. Such concordance
has not been achieved for models of enhancer function in eukaryotes. In equilibrium
models, it is difficult to reconcile the reported short transcription factor (TF)
residence times on the DNA with the high specificity of regulation. In nonequilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal nonequilibrium enhancer
models that yield desired regulatory phenotypes: low TF residence time, high specificity,
and tunable cooperativity. We find that a single extra parameter, interpretable
as the “linking rate,” by which bound TFs interact with Mediator components, enables
our models to escape equilibrium bounds and access optimal regulatory phenotypes,
while remaining consistent with the reported phenomenology and simple enough to
be inferred from upcoming experiments. We further find that high specificity in
nonequilibrium models is in a trade-off with gene-expression noise, predicting
bursty dynamics—an experimentally observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space of nonequilibrium enhancer models
to a much smaller subspace that optimally realizes biological function, we deliver
a rich class of models that could be tractably inferred from data in the near
future.'
acknowledgement: G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018.
R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks
S. Avvakumov for helpful discussions.
article_processing_charge: No
article_type: original
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function.
PNAS. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal
enhancer function. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of
Optimal Enhancer Function.” PNAS. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer
function,” PNAS, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622,
2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer
function. PNAS. 117(50), 31614–31622.
mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS,
vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117.
short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622.
date_created: 2021-01-10T23:01:17Z
date_published: 2020-12-15T00:00:00Z
date_updated: 2023-08-24T11:10:22Z
day: '15'
ddc:
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department:
- _id: GaTk
doi: 10.1073/pnas.2006731117
external_id:
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pmid:
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grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/
scopus_import: '1'
status: public
title: Nonequilibrium models of optimal enhancer function
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
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user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
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...
---
_id: '8084'
abstract:
- lang: eng
text: Origin and functions of intermittent transitions among sleep stages, including
brief awakenings and arousals, constitute a challenge to the current homeostatic
framework for sleep regulation, focusing on factors modulating sleep over large
time scales. Here we propose that the complex micro-architecture characterizing
sleep on scales of seconds and minutes results from intrinsic non-equilibrium
critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in
rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned
(male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms
exhibit complex temporal organization, with long-range correlations and robust
duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts,
quiescent phase) duration distributions, features typical of non-equilibrium systems
self-organizing at criticality. We show that such non-equilibrium behavior relates
to anti-correlated coupling between θ- and δ-bursts, persists across a range of
time scales, and is independent of the dominant physiologic state; indications
of a basic principle in sleep regulation. Further, we find that VLPO lesions lead
to a modulation of cortical dynamics resulting in altered dynamical parameters
of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings
and model simulations demonstrate that θ–δ coupling is essential for the emerging
non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate
that VLPO neurons may have dual role for both sleep and arousal/brief wake activation.
The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates
a mechanism essential for the micro-architecture of spontaneous sleep-stage and
arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.
article_processing_charge: No
article_type: original
author:
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Manuel
full_name: Gómez-Extremera, Manuel
last_name: Gómez-Extremera
- first_name: Pedro
full_name: Bernaola-Galván, Pedro
last_name: Bernaola-Galván
- first_name: Ramalingam
full_name: Vetrivelan, Ramalingam
last_name: Vetrivelan
- first_name: Clifford B.
full_name: Saper, Clifford B.
last_name: Saper
- first_name: Thomas E.
full_name: Scammell, Thomas E.
last_name: Scammell
- first_name: Plamen Ch.
full_name: Ivanov, Plamen Ch.
last_name: Ivanov
citation:
ama: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics
and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism
for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake.
Journal of Neuroscience. 2020;40(1):171-190. doi:10.1523/jneurosci.1278-19.2019
apa: Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper,
C. B., Scammell, T. E., & Ivanov, P. C. (2020). Critical dynamics and coupling
in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage
transitions and dual role of VLPO neurons in both sleep and wake. Journal of
Neuroscience. Society for Neuroscience. https://doi.org/10.1523/jneurosci.1278-19.2019
chicago: Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam
Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical
Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism
for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.”
Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/jneurosci.1278-19.2019.
ieee: F. Lombardi et al., “Critical dynamics and coupling in bursts of cortical
rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
role of VLPO neurons in both sleep and wake,” Journal of Neuroscience,
vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020.
ista: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB,
Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical
rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190.
mla: Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical
Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual
Role of VLPO Neurons in Both Sleep and Wake.” Journal of Neuroscience,
vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:10.1523/jneurosci.1278-19.2019.
short: F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B.
Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190.
date_created: 2020-07-05T15:24:51Z
date_published: 2020-01-02T00:00:00Z
date_updated: 2023-09-05T14:02:55Z
day: '02'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1523/jneurosci.1278-19.2019
ec_funded: 1
external_id:
isi:
- '000505167600016'
pmid:
- '31694962'
file:
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content_type: application/pdf
creator: dernst
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date_updated: 2020-07-22T11:44:48Z
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oa_version: Published Version
page: 171-190
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- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Journal of Neuroscience
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eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic
mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep
and wake
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 40
year: '2020'
...
---
_id: '8155'
abstract:
- lang: eng
text: "In the thesis we focus on the interplay of the biophysics and evolution of
gene regulation. We start by addressing how the type of prokaryotic gene regulation
– activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional
crosstalk. We propose that regulatory interference caused by excess regulatory
proteins in the dense cellular medium – global crosstalk – could be a factor in
determining which type of gene regulatory network is evolutionarily preferred.
Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium
enhancer models that optimize so-called regulatory phenotypes. We find a class
of models that differ from standard thermodynamic equilibrium models by a single
parameter that notably increases the regulatory performance. Next chapter addresses
the question of genotype-phenotype-fitness maps of higher dimensional phenotypes.
We show that our biophysically realistic approach allows us to understand how
the mechanisms of promoter function constrain genotypephenotype maps, and how
they affect the evolutionary trajectories of promoters.\r\nIn the last chapter
we ask whether the intrinsic instability of gene duplication and amplification
provides a generic alternative to canonical gene regulation. Using mathematical
modeling, we show that amplifications can tune gene expression in many environments,
including those where transcription factor-based schemes are\r\nhard to evolve
or maintain. "
acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship
of the Austrian Academy of Sciences.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
citation:
ama: Grah R. Gene regulation across scales – how biophysical constraints shape evolution.
2020. doi:10.15479/AT:ISTA:8155
apa: Grah, R. (2020). Gene regulation across scales – how biophysical constraints
shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155
chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints
Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155.
ieee: R. Grah, “Gene regulation across scales – how biophysical constraints shape
evolution,” Institute of Science and Technology Austria, 2020.
ista: Grah R. 2020. Gene regulation across scales – how biophysical constraints
shape evolution. Institute of Science and Technology Austria.
mla: Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape
Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155.
short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape
Evolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-07-23T09:51:28Z
date_published: 2020-07-24T00:00:00Z
date_updated: 2023-09-07T13:13:27Z
day: '24'
ddc:
- '530'
- '570'
degree_awarded: PhD
department:
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- _id: GaTk
doi: 10.15479/AT:ISTA:8155
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name: Biophysically realistic genotype-phenotype maps for regulatory networks
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status: public
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relation: part_of_dissertation
status: public
status: public
supervisor:
- 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
title: Gene regulation across scales – how biophysical constraints shape evolution
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '7675'
abstract:
- lang: eng
text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
quantitative mapping from promoter sequences to gene expression levels that is
compatible with in vivo and in vitro bio-physical measurements. Such concordance
has not been achieved for models of enhancer function in eukaryotes. In equilibrium
models, it is difficult to reconcile the reported short transcription factor (TF)
residence times on the DNA with the high specificity of regulation. In non-equilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal non-equilibrium enhancer
models that yield desired regulatory phenotypes: low TF residence time, high specificity
and tunable cooperativity. We find that a single extra parameter, interpretable
as the “linking rate” by which bound TFs interact with Mediator components, enables
our models to escape equilibrium bounds and access optimal regulatory phenotypes,
while remaining consistent with the reported phenomenology and simple enough to
be inferred from upcoming experiments. We further find that high specificity in
non-equilibrium models is in a tradeoff with gene expression noise, predicting
bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space to a much smaller subspace that
optimally realizes biological function prior to inference from data, our normative
approach holds promise for mathematical models in systems biology.'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv.
2020. doi:10.1101/2020.04.08.029405
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer
function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer
Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,”
bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv,
10.1101/2020.04.08.029405.
mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv,
Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405.
short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).
date_created: 2020-04-23T10:12:51Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2023-09-07T13:13:26Z
day: '09'
department:
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- _id: GaTk
doi: 10.1101/2020.04.08.029405
language:
- iso: eng
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month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 2665AAFE-B435-11E9-9278-68D0E5697425
grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
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record:
- id: '8155'
relation: dissertation_contains
status: public
status: public
title: Normative models of enhancer function
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...