---
_id: '15033'
abstract:
- lang: eng
text: The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF)
is among the best studied trafficking regulators in plants, playing crucial and
unique developmental roles in patterning and polarity. The current models place
GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at
the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis
(CME). The mechanistic basis of the developmental function of GN, distinct from
the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains
elusive. Insights from this study largely extend the current notions of GN function.
We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures
distinct from clathrin-coated pits, while CME and secretion proceed normally in
gn knockouts. The functional GN mutant variant GNfewerroots,
absent from the GA, suggests that the cell periphery is the major site of GN action
responsible for its developmental function. Following inhibition by Brefeldin
A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting
selective molecular associations en route to the cell periphery. A study of GN-GNL1
chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN
function in a partially redundant manner. Together, this study offers significant
steps toward the elucidation of the mechanism underlying unique cellular and development
functions of GNOM.
acknowledgement: "The authors would like to gratefully acknowledge Dr Xixi Zhang for
cloning the GNL1/pDONR221 construct and for useful discussions.H2020 European Research\r\nCouncil
Advanced Grant ETAP742985 to Jiří Friml, Austrian Science Fund I 3630-B25 to Jiří
Friml"
article_processing_charge: Yes
article_type: original
author:
- first_name: Maciek
full_name: Adamowski, Maciek
id: 45F536D2-F248-11E8-B48F-1D18A9856A87
last_name: Adamowski
orcid: 0000-0001-6463-5257
- first_name: Ivana
full_name: Matijevic, Ivana
id: 83c17ce3-15b2-11ec-abd3-f486545870bd
last_name: Matijevic
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
citation:
ama: Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM
ARF-GEF mediated from the cell periphery. eLife. 2024;13. doi:10.7554/elife.68993
apa: Adamowski, M., Matijevic, I., & Friml, J. (2024). Developmental patterning
function of GNOM ARF-GEF mediated from the cell periphery. ELife. eLife
Sciences Publications. https://doi.org/10.7554/elife.68993
chicago: Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning
Function of GNOM ARF-GEF Mediated from the Cell Periphery.” ELife. eLife
Sciences Publications, 2024. https://doi.org/10.7554/elife.68993.
ieee: M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function
of GNOM ARF-GEF mediated from the cell periphery,” eLife, vol. 13. eLife
Sciences Publications, 2024.
ista: Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function
of GNOM ARF-GEF mediated from the cell periphery. eLife. 13.
mla: Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF
Mediated from the Cell Periphery.” ELife, vol. 13, eLife Sciences Publications,
2024, doi:10.7554/elife.68993.
short: M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024).
date_created: 2024-02-27T07:10:11Z
date_published: 2024-02-21T00:00:00Z
date_updated: 2024-02-28T12:29:43Z
day: '21'
ddc:
- '580'
department:
- _id: JiFr
doi: 10.7554/elife.68993
ec_funded: 1
has_accepted_license: '1'
intvolume: ' 13'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.7554/eLife.68993
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 26538374-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03630
name: Molecular mechanisms of endocytic cargo recognition in plants
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: epub_ahead
publisher: eLife Sciences Publications
quality_controlled: '1'
status: public
title: Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery
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: 13
year: '2024'
...
---
_id: '14683'
abstract:
- lang: eng
text: "Mosaic analysis with double markers (MADM) technology enables the generation
of genetic mosaic tissue in mice and high-resolution phenotyping at the individual
cell level. Here, we present a protocol for isolating MADM-labeled cells with
high yield for downstream molecular analyses using fluorescence-activated cell
sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion,
single-cell suspension, and debris removal. We then detail procedures for cell
sorting by FACS and downstream analysis. This protocol is suitable for embryonic
to adult mice.\r\nFor complete details on the use and execution of this protocol,
please refer to Contreras et al. (2021).1"
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Imaging & Optics Facility (IOF)
and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme
(T 1031). G.C. received support from the European Union’s Horizon 2020 research
and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411
as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional
funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780
LinPro) to S.H.
article_number: '102771'
article_processing_charge: No
article_type: review
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains
labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols.
2023;5(1). doi:10.1016/j.xpro.2023.102771
apa: Amberg, N., Cheung, G. T., & Hippenmeyer, S. (2023). Protocol for sorting
cells from mouse brains labeled with mosaic analysis with double markers by flow
cytometry. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102771
chicago: Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for
Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers
by Flow Cytometry.” STAR Protocols. Elsevier, 2023. https://doi.org/10.1016/j.xpro.2023.102771.
ieee: N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from
mouse brains labeled with mosaic analysis with double markers by flow cytometry,”
STAR Protocols, vol. 5, no. 1. Elsevier, 2023.
ista: Amberg N, Cheung GT, Hippenmeyer S. 2023. Protocol for sorting cells from
mouse brains labeled with mosaic analysis with double markers by flow cytometry.
STAR Protocols. 5(1), 102771.
mla: Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled
with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols,
vol. 5, no. 1, 102771, Elsevier, 2023, doi:10.1016/j.xpro.2023.102771.
short: N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023).
date_created: 2023-12-13T11:48:05Z
date_published: 2023-12-08T00:00:00Z
date_updated: 2023-12-18T08:06:14Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2023.102771
ec_funded: 1
external_id:
pmid:
- '38070137'
intvolume: ' 5'
issue: '1'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.xpro.2023.102771
month: '12'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: STAR Protocols
publication_identifier:
issn:
- 2666-1667
publication_status: epub_ahead
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Protocol for sorting cells from mouse brains labeled with mosaic analysis with
double markers by flow cytometry
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: 5
year: '2023'
...
---
_id: '12562'
abstract:
- lang: eng
text: Presynaptic inputs determine the pattern of activation of postsynaptic neurons
in a neural circuit. Molecular and genetic pathways that regulate the selective
formation of subsets of presynaptic inputs are largely unknown, despite significant
understanding of the general process of synaptogenesis. In this study, we have
begun to identify such factors using the spinal monosynaptic stretch reflex circuit
as a model system. In this neuronal circuit, Ia proprioceptive afferents establish
monosynaptic connections with spinal motor neurons that project to the same muscle
(termed homonymous connections) or muscles with related or synergistic function.
However, monosynaptic connections are not formed with motor neurons innervating
muscles with antagonistic functions. The ETS transcription factor ER81 (also known
as ETV1) is expressed by all proprioceptive afferents, but only a small set of
motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional
mouse genetic techniques to eliminate Er81 expression selectively from motor neurons.
We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive
afferents conveying information from homonymous and synergistic muscles, with
no change observed in the connectivity pattern from antagonistic proprioceptive
afferents. In summary, these findings suggest a role for ER81 in defined motor
neuron pools to control the assembly of specific presynaptic inputs and thereby
influence the profile of activation of these motor neurons.
acknowledgement: The authors gratefully thank Dr. Silvia Arber, University of Basel
and Friedrich Miescher Institute for Biomedical Research, for support and in whose
lab the data were collected. For advice on statistical analysis, we thank Michael
Bottomley from the Statistical Consulting Center, College of Science and Mathematics,
Wright State University.
article_processing_charge: No
article_type: original
author:
- first_name: David R.
full_name: Ladle, David R.
last_name: Ladle
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Ladle DR, Hippenmeyer S. Loss of ETV1/ER81 in motor neurons leads to reduced
monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology.
2023;129(3):501-512. doi:10.1152/jn.00172.2022
apa: Ladle, D. R., & Hippenmeyer, S. (2023). Loss of ETV1/ER81 in motor neurons
leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal
of Neurophysiology. American Physiological Society. https://doi.org/10.1152/jn.00172.2022
chicago: Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons
Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” Journal
of Neurophysiology. American Physiological Society, 2023. https://doi.org/10.1152/jn.00172.2022.
ieee: D. R. Ladle and S. Hippenmeyer, “Loss of ETV1/ER81 in motor neurons leads
to reduced monosynaptic inputs from proprioceptive sensory neurons,” Journal
of Neurophysiology, vol. 129, no. 3. American Physiological Society, pp. 501–512,
2023.
ista: Ladle DR, Hippenmeyer S. 2023. Loss of ETV1/ER81 in motor neurons leads to
reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology.
129(3), 501–512.
mla: Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons
Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” Journal
of Neurophysiology, vol. 129, no. 3, American Physiological Society, 2023,
pp. 501–12, doi:10.1152/jn.00172.2022.
short: D.R. Ladle, S. Hippenmeyer, Journal of Neurophysiology 129 (2023) 501–512.
date_created: 2023-02-15T14:46:14Z
date_published: 2023-03-01T00:00:00Z
date_updated: 2023-09-05T12:13:34Z
day: '01'
department:
- _id: SiHi
doi: 10.1152/jn.00172.2022
external_id:
isi:
- '000957721600001'
pmid:
- '36695533'
intvolume: ' 129'
isi: 1
issue: '3'
keyword:
- Physiology
- General Neuroscience
language:
- iso: eng
month: '03'
oa_version: None
page: 501-512
pmid: 1
publication: Journal of Neurophysiology
publication_identifier:
eissn:
- 1522-1598
issn:
- 0022-3077
publication_status: published
publisher: American Physiological Society
quality_controlled: '1'
status: public
title: Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from
proprioceptive sensory neurons
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 129
year: '2023'
...
---
_id: '12679'
abstract:
- lang: eng
text: How to generate a brain of correct size and with appropriate cell-type diversity
during development is a major question in Neuroscience. In the developing neocortex,
radial glial progenitor (RGP) cells are the main neural stem cells that produce
cortical excitatory projection neurons, glial cells, and establish the prospective
postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated
developmental program that when disrupted can result in severe cortical malformations
such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms
instructing faithful RGP lineage progression are however not well understood.
This review will summarize recent conceptual advances that contribute to our understanding
of the general principles of RGP lineage progression.
acknowledgement: "I wish to thank all current and past members of the Hippenmeyer
laboratory at ISTA for exciting discussions on the subject of this review. I apologize
to colleagues whose work I could not cite and/or discuss in the frame of the available
space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported
by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council
(ERC) under the European Union’s Horizon 2020 Research and Innovation Programme
(grant agree-ment no. 725780 LinPro) to SH."
article_number: '102695'
article_processing_charge: Yes (via OA deal)
article_type: review
author:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: 'Hippenmeyer S. Principles of neural stem cell lineage progression: Insights
from developing cerebral cortex. Current Opinion in Neurobiology. 2023;79(4).
doi:10.1016/j.conb.2023.102695'
apa: 'Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression:
Insights from developing cerebral cortex. Current Opinion in Neurobiology.
Elsevier. https://doi.org/10.1016/j.conb.2023.102695'
chicago: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression:
Insights from Developing Cerebral Cortex.” Current Opinion in Neurobiology.
Elsevier, 2023. https://doi.org/10.1016/j.conb.2023.102695.'
ieee: 'S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights
from developing cerebral cortex,” Current Opinion in Neurobiology, vol.
79, no. 4. Elsevier, 2023.'
ista: 'Hippenmeyer S. 2023. Principles of neural stem cell lineage progression:
Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4),
102695.'
mla: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights
from Developing Cerebral Cortex.” Current Opinion in Neurobiology, vol.
79, no. 4, 102695, Elsevier, 2023, doi:10.1016/j.conb.2023.102695.'
short: S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).
date_created: 2023-02-26T12:24:21Z
date_published: 2023-04-01T00:00:00Z
date_updated: 2023-08-16T12:30:25Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.conb.2023.102695
ec_funded: 1
external_id:
isi:
- '000953497700001'
pmid:
- '36842274'
file:
- access_level: open_access
checksum: 4d11c4ca87e6cbc4d2ac46d3225ea615
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T12:29:06Z
date_updated: 2023-08-16T12:29:06Z
file_id: '14071'
file_name: 2023_CurrentOpinionNeurobio_Hippenmeyer.pdf
file_size: 1787894
relation: main_file
success: 1
file_date_updated: 2023-08-16T12:29:06Z
has_accepted_license: '1'
intvolume: ' 79'
isi: 1
issue: '4'
keyword:
- General Neuroscience
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Current Opinion in Neurobiology
publication_identifier:
issn:
- 0959-4388
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Principles of neural stem cell lineage progression: Insights from developing
cerebral cortex'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 79
year: '2023'
...
---
_id: '11447'
abstract:
- lang: eng
text: Empirical essays of fitness landscapes suggest that they may be rugged, that
is having multiple fitness peaks. Such fitness landscapes, those that have multiple
peaks, necessarily have special local structures, called reciprocal sign epistasis
(Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the
quantitative relationship between the number of fitness peaks and the number of
reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk
et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis
is a necessary but not sufficient condition for the existence of multiple peaks.
Applying discrete Morse theory, which to our knowledge has never been used in
this context, we extend this result by giving the minimal number of reciprocal
sign epistatic interactions required to create a given number of peaks.
acknowledgement: We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful
discussions. Open access funding provided by Austrian Science Fund (FWF). Partially
supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund
(I5127-B) grants to FAK.
article_number: '74'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Raimundo J
full_name: Saona Urmeneta, Raimundo J
id: BD1DF4C4-D767-11E9-B658-BC13E6697425
last_name: Saona Urmeneta
orcid: 0000-0001-5103-038X
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
- first_name: Kseniia
full_name: Khudiakova, Kseniia
id: 4E6DC800-AE37-11E9-AC72-31CAE5697425
last_name: Khudiakova
orcid: 0000-0002-6246-1465
citation:
ama: Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number
of peaks and the number of reciprocal sign epistatic interactions. Bulletin
of Mathematical Biology. 2022;84(8). doi:10.1007/s11538-022-01029-z
apa: Saona Urmeneta, R. J., Kondrashov, F., & Khudiakova, K. (2022). Relation
between the number of peaks and the number of reciprocal sign epistatic interactions.
Bulletin of Mathematical Biology. Springer Nature. https://doi.org/10.1007/s11538-022-01029-z
chicago: Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova.
“Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic
Interactions.” Bulletin of Mathematical Biology. Springer Nature, 2022.
https://doi.org/10.1007/s11538-022-01029-z.
ieee: R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between
the number of peaks and the number of reciprocal sign epistatic interactions,”
Bulletin of Mathematical Biology, vol. 84, no. 8. Springer Nature, 2022.
ista: Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the
number of peaks and the number of reciprocal sign epistatic interactions. Bulletin
of Mathematical Biology. 84(8), 74.
mla: Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and
the Number of Reciprocal Sign Epistatic Interactions.” Bulletin of Mathematical
Biology, vol. 84, no. 8, 74, Springer Nature, 2022, doi:10.1007/s11538-022-01029-z.
short: R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical
Biology 84 (2022).
date_created: 2022-06-17T16:16:15Z
date_published: 2022-06-17T00:00:00Z
date_updated: 2023-08-03T07:20:53Z
day: '17'
ddc:
- '510'
- '570'
department:
- _id: GradSch
- _id: NiBa
- _id: JaMa
doi: 10.1007/s11538-022-01029-z
ec_funded: 1
external_id:
isi:
- '000812509800001'
file:
- access_level: open_access
checksum: 05a1fe7d10914a00c2bca9b447993a65
content_type: application/pdf
creator: dernst
date_created: 2022-06-20T07:51:32Z
date_updated: 2022-06-20T07:51:32Z
file_id: '11455'
file_name: 2022_BulletinMathBiology_Saona.pdf
file_size: 463025
relation: main_file
success: 1
file_date_updated: 2022-06-20T07:51:32Z
has_accepted_license: '1'
intvolume: ' 84'
isi: 1
issue: '8'
keyword:
- Computational Theory and Mathematics
- General Agricultural and Biological Sciences
- Pharmacology
- General Environmental Science
- General Biochemistry
- Genetics and Molecular Biology
- General Mathematics
- Immunology
- General Neuroscience
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771209'
name: Characterizing the fitness landscape on population and global scales
- _id: c098eddd-5a5b-11eb-8a69-abe27170a68f
grant_number: I05127
name: Evolutionary analysis of gene regulation
publication: Bulletin of Mathematical Biology
publication_identifier:
eissn:
- 1522-9602
issn:
- 0092-8240
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1007/s11538-022-01118-z
scopus_import: '1'
status: public
title: Relation between the number of peaks and the number of reciprocal sign epistatic
interactions
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: 84
year: '2022'
...
---
_id: '11448'
abstract:
- lang: eng
text: Studies of protein fitness landscapes reveal biophysical constraints guiding
protein evolution and empower prediction of functional proteins. However, generalisation
of these findings is limited due to scarceness of systematic data on fitness landscapes
of proteins with a defined evolutionary relationship. We characterized the fitness
peaks of four orthologous fluorescent proteins with a broad range of sequence
divergence. While two of the four studied fitness peaks were sharp, the other
two were considerably flatter, being almost entirely free of epistatic interactions.
Mutationally robust proteins, characterized by a flat fitness peak, were not optimal
templates for machine-learning-driven protein design – instead, predictions were
more accurate for fragile proteins with epistatic landscapes. Our work paves insights
for practical application of fitness landscape heterogeneity in protein engineering.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: "We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić
and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo
for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com)
for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova
for technical assistance and data interpretation. Core facility Biomolecular Interactions
and Crystallization of CEITEC Masaryk University is gratefully acknowledged for
the obtaining of the scientific data presented in this paper. This research was
supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources
provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF).
MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility
at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC),
Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular
Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility
in the Vanderbilt University Center for Structural Biology. We are grateful to Joel
M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator
grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4,
the Imperial College Research Fellowship and the MRC London Institute of Medical
Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie
Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\").
Experiments were partially carried out using equipment provided by the Institute
of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH).
This work was supported by a Russian Science Foundation grant 19-74-10102.This project
has received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385."
article_number: '75842'
article_processing_charge: No
article_type: original
author:
- first_name: Louisa
full_name: Gonzalez Somermeyer, Louisa
id: 4720D23C-F248-11E8-B48F-1D18A9856A87
last_name: Gonzalez Somermeyer
orcid: 0000-0001-9139-5383
- first_name: Aubin
full_name: Fleiss, Aubin
last_name: Fleiss
- first_name: Alexander S
full_name: Mishin, Alexander S
last_name: Mishin
- first_name: Nina G
full_name: Bozhanova, Nina G
last_name: Bozhanova
- first_name: Anna A
full_name: Igolkina, Anna A
last_name: Igolkina
- first_name: Jens
full_name: Meiler, Jens
last_name: Meiler
- first_name: Maria-Elisenda
full_name: Alaball Pujol, Maria-Elisenda
last_name: Alaball Pujol
- first_name: Ekaterina V
full_name: Putintseva, Ekaterina V
last_name: Putintseva
- first_name: Karen S
full_name: Sarkisyan, Karen S
last_name: Sarkisyan
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP
fitness landscape and data-driven protein design. eLife. 2022;11. doi:10.7554/elife.75842
apa: Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina,
A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape
and data-driven protein design. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.75842
chicago: Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova,
Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva,
Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape
and Data-Driven Protein Design.” ELife. eLife Sciences Publications, 2022.
https://doi.org/10.7554/elife.75842.
ieee: L. Gonzalez Somermeyer et al., “Heterogeneity of the GFP fitness landscape
and data-driven protein design,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler
J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity
of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.
mla: Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape
and Data-Driven Protein Design.” ELife, vol. 11, 75842, eLife Sciences
Publications, 2022, doi:10.7554/elife.75842.
short: L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina,
J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov,
ELife 11 (2022).
date_created: 2022-06-18T09:06:59Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2023-08-03T07:20:15Z
day: '05'
ddc:
- '570'
department:
- _id: GradSch
- _id: FyKo
doi: 10.7554/elife.75842
ec_funded: 1
external_id:
isi:
- '000799197200001'
file:
- access_level: open_access
checksum: 7573c28f44028ab0cc81faef30039e44
content_type: application/pdf
creator: dernst
date_created: 2022-06-20T07:44:19Z
date_updated: 2022-06-20T07:44:19Z
file_id: '11454'
file_name: 2022_eLife_Somermeyer.pdf
file_size: 5297213
relation: main_file
success: 1
file_date_updated: 2022-06-20T07:44:19Z
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: '05'
oa: 1
oa_version: Published Version
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771209'
name: Characterizing the fitness landscape on population and global scales
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Heterogeneity of the GFP fitness landscape and data-driven protein design
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: '12117'
abstract:
- lang: eng
text: "To understand how potential gene manipulations affect in vitro microglia,
we provide a set of short protocols to evaluate microglia identity and function.
We detail steps for immunostaining to determine microglia identity. We describe
three functional assays for microglia: phagocytosis, calcium response following
ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these
protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but
they can be also applied to other in vitro microglial models including primary
mouse microglia.\r\nFor complete details on the use and execution of this protocol,
please refer to Bartalska et al. (2022).1"
acknowledged_ssus:
- _id: Bio
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich
(grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for
their insights into functional assays and data analysis, Verena Seiboth for insights
into necessary institutional permission, and ISTA imaging & optics facility (IOF)
especially Bernhard Hochreiter for their support.
article_number: '101866'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Verena
full_name: Hübschmann, Verena
id: 32B7C918-F248-11E8-B48F-1D18A9856A87
last_name: Hübschmann
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity
and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866
apa: Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived
microglia identity and function by immunostaining, phagocytosis, calcium activity,
and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866
chicago: Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human
IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis,
Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022.
https://doi.org/10.1016/j.xpro.2022.101866.
ieee: V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia
identity and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022.
ista: Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia
identity and function by immunostaining, phagocytosis, calcium activity, and inflammation
assay. STAR Protocols. 3(4), 101866.
mla: Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity
and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation
Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866.
short: V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).
date_created: 2023-01-12T11:56:38Z
date_published: 2022-12-16T00:00:00Z
date_updated: 2023-11-02T12:21:32Z
day: '16'
ddc:
- '570'
department:
- _id: SaSi
- _id: GradSch
doi: 10.1016/j.xpro.2022.101866
ec_funded: 1
file:
- access_level: open_access
checksum: 3c71b8a60633d42c2f77c49025d5559b
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T09:50:51Z
date_updated: 2023-01-23T09:50:51Z
file_id: '12340'
file_name: 2022_STARProtocols_Huebschmann.pdf
file_size: 6251945
relation: main_file
success: 1
file_date_updated: 2023-01-23T09:50:51Z
has_accepted_license: '1'
intvolume: ' 3'
issue: '4'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
- _id: 9B99D380-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-017
name: How human microglia shape developing neurons during health and inflammation
publication: STAR Protocols
publication_identifier:
issn:
- 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '11478'
relation: other
status: public
scopus_import: '1'
status: public
title: Assessing human iPSC-derived microglia identity and function by immunostaining,
phagocytosis, calcium activity, and inflammation assay
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 3
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.
eLife. 2022;11. doi:10.7554/elife.66697
apa: Hayward, L., & Sella, G. (2022). Polygenic adaptation after a sudden change
in environment. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.66697
chicago: Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change
in Environment.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.66697.
ieee: L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,”
eLife, 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.” ELife, vol. 11, 66697, eLife Sciences Publications, 2022,
doi:10.7554/elife.66697.
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: '12244'
abstract:
- lang: eng
text: Environmental cues influence the highly dynamic morphology of microglia. Strategies
to characterize these changes usually involve user-selected morphometric features,
which preclude the identification of a spectrum of context-dependent morphological
phenotypes. Here we develop MorphOMICs, a topological data analysis approach,
which enables semiautomatic mapping of microglial morphology into an atlas of
cue-dependent phenotypes and overcomes feature-selection biases and biological
variability. We extract spatially heterogeneous and sexually dimorphic morphological
phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines
with maturation but increases over the disease trajectories in two neurodegeneration
mouse models, with females showing a faster morphological shift in affected brain
regions. Remarkably, microglia morphologies reflect an adaptation upon repeated
exposure to ketamine anesthesia and do not recover to control morphologies. Finally,
we demonstrate that both long primary processes and short terminal processes provide
distinct insights to morphological phenotypes. MorphOMICs opens a new perspective
to characterize microglial morphology.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
acknowledgement: We thank the scientific service units at ISTA, in particular M. Schunn’s
team at the preclinical facility, and especially our colony manager S. Haslinger,
for excellent support. We are also grateful to the ISTA Imaging & Optics Facility,
and in particular C. Sommer for helping with the data file conversions. We thank
R. Erhart from the ISTA Scientific Computing Unit for improving the script performance.
We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert
group for constant feedback on the project and on the manuscript. This research
was supported by the European Union Horizon 2020 research and innovation program
under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the
European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding
to the Blue Brain Project, a research center of the École polytechnique fédérale
de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes
of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB
Foundation. The funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript.
article_processing_charge: No
article_type: original
author:
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Lida
full_name: Kanari, Lida
last_name: Kanari
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Martina
full_name: Scolamiero, Martina
last_name: Scolamiero
- first_name: Jens
full_name: Agerberg, Jens
last_name: Agerberg
- first_name: Hansruedi
full_name: Mathys, Hansruedi
last_name: Mathys
- first_name: Li-Huei
full_name: Tsai, Li-Huei
last_name: Tsai
- first_name: Wojciech
full_name: Chachólski, Wojciech
last_name: Chachólski
- first_name: Kathryn
full_name: Hess, Kathryn
last_name: Hess
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology,
morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
2022;25(10):1379-1393. doi:10.1038/s41593-022-01167-6
apa: Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero,
M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
Springer Nature. https://doi.org/10.1038/s41593-022-01167-6
chicago: Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven
Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial
Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature
Neuroscience. Springer Nature, 2022. https://doi.org/10.1038/s41593-022-01167-6.
ieee: G. Colombo et al., “A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes,” Nature Neuroscience,
vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.
ista: Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg
J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping
microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes.
Nature Neuroscience. 25(10), 1379–1393.
mla: Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs,
Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature Neuroscience,
vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:10.1038/s41593-022-01167-6.
short: G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero,
J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature
Neuroscience 25 (2022) 1379–1393.
date_created: 2023-01-16T09:53:07Z
date_published: 2022-10-01T00:00:00Z
date_updated: 2024-03-25T23:30:10Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41593-022-01167-6
ec_funded: 1
external_id:
isi:
- '000862214700001'
pmid:
- '36180790'
file:
- access_level: open_access
checksum: 28431146873096f52e0107b534f178c9
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T08:06:56Z
date_updated: 2023-01-30T08:06:56Z
file_id: '12437'
file_name: 2022_NatureNeuroscience_Colombo.pdf
file_size: 23789835
relation: main_file
success: 1
file_date_updated: 2023-01-30T08:06:56Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '10'
keyword:
- General Neuroscience
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 1379-1393
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Nature Neuroscience
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/
record:
- id: '12378'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A tool for mapping microglial morphology, morphOMICs, reveals brain-region
and sex-dependent phenotypes
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: 25
year: '2022'
...
---
_id: '12251'
abstract:
- lang: eng
text: Amyloid formation is linked to devastating neurodegenerative diseases, motivating
detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated
with Alzheimer’s disease, the mechanism and rate of aggregation have been established
for a range of variants and conditions in vitro and
in bodily fluids. A key outstanding question is how the relative stabilities of
monomers, fibrils and intermediates affect each step in the fibril formation process.
By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or
guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying
microscopic steps and establish the importance of changes in relative stability
induced by the presence of denaturant for each individual step. Denaturants shift
the equilibrium towards the unfolded state of each species. We find that a non-ionic
denaturant, urea, reduces the overall aggregation rate, and that the effect on
nucleation is stronger than the effect on elongation. Urea reduces the rate of
secondary nucleation by decreasing the coverage of fibril surfaces and the rate
of nucleus formation. It also reduces the rate of primary nucleation, increasing
its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at
low denaturant concentrations and decelerates the aggregation at high denaturant
concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic
interactions between peptides by the charged denaturant dominates, leading to
an increased aggregation rate. At higher GuHCl concentrations, the electrostatic
repulsion is completely screened, and the denaturing effect dominates. The results
illustrate how the differential effects of denaturants on stability of monomer,
oligomer and fibril translate to differential effects on microscopic steps, with
the rate of nucleation being most strongly reduced.
acknowledgement: This work was supported by grants from the Swedish Research Council
(grant no. 2015-00143) and the European Research Council (grant no. 340890).
article_number: '943355'
article_processing_charge: No
article_type: original
author:
- first_name: Tanja
full_name: Weiffert, Tanja
last_name: Weiffert
- first_name: Georg
full_name: Meisl, Georg
last_name: Meisl
- first_name: Samo
full_name: Curk, Samo
last_name: Curk
- first_name: Risto
full_name: Cukalevski, Risto
last_name: Cukalevski
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Tuomas P. J.
full_name: Knowles, Tuomas P. J.
last_name: Knowles
- first_name: Sara
full_name: Linse, Sara
last_name: Linse
citation:
ama: Weiffert T, Meisl G, Curk S, et al. Influence of denaturants on amyloid β42
aggregation kinetics. Frontiers in Neuroscience. 2022;16. doi:10.3389/fnins.2022.943355
apa: Weiffert, T., Meisl, G., Curk, S., Cukalevski, R., Šarić, A., Knowles, T. P.
J., & Linse, S. (2022). Influence of denaturants on amyloid β42 aggregation
kinetics. Frontiers in Neuroscience. Frontiers Media. https://doi.org/10.3389/fnins.2022.943355
chicago: Weiffert, Tanja, Georg Meisl, Samo Curk, Risto Cukalevski, Anđela Šarić,
Tuomas P. J. Knowles, and Sara Linse. “Influence of Denaturants on Amyloid Β42
Aggregation Kinetics.” Frontiers in Neuroscience. Frontiers Media, 2022.
https://doi.org/10.3389/fnins.2022.943355.
ieee: T. Weiffert et al., “Influence of denaturants on amyloid β42 aggregation
kinetics,” Frontiers in Neuroscience, vol. 16. Frontiers Media, 2022.
ista: Weiffert T, Meisl G, Curk S, Cukalevski R, Šarić A, Knowles TPJ, Linse S.
2022. Influence of denaturants on amyloid β42 aggregation kinetics. Frontiers
in Neuroscience. 16, 943355.
mla: Weiffert, Tanja, et al. “Influence of Denaturants on Amyloid Β42 Aggregation
Kinetics.” Frontiers in Neuroscience, vol. 16, 943355, Frontiers Media,
2022, doi:10.3389/fnins.2022.943355.
short: T. Weiffert, G. Meisl, S. Curk, R. Cukalevski, A. Šarić, T.P.J. Knowles,
S. Linse, Frontiers in Neuroscience 16 (2022).
date_created: 2023-01-16T09:56:43Z
date_published: 2022-09-20T00:00:00Z
date_updated: 2023-08-04T09:48:56Z
day: '20'
ddc:
- '570'
department:
- _id: AnSa
doi: 10.3389/fnins.2022.943355
external_id:
isi:
- '000866287100001'
file:
- access_level: open_access
checksum: e67d16113ffb4fb4fa38a183d169f210
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T09:15:13Z
date_updated: 2023-01-30T09:15:13Z
file_id: '12442'
file_name: 2022_FrontiersNeuroscience_Weiffert2.pdf
file_size: 19798610
relation: main_file
success: 1
file_date_updated: 2023-01-30T09:15:13Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
keyword:
- General Neuroscience
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Frontiers in Neuroscience
publication_identifier:
issn:
- 1662-453X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Influence of denaturants on amyloid β42 aggregation kinetics
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: 16
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. eLife. 2022;11. doi:10.7554/elife.79848
apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast,
high-throughput production of improved rabies viral vectors for specific, efficient
and versatile transsynaptic retrograde labeling. ELife. eLife Sciences
Publications. https://doi.org/10.7554/elife.79848
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.” ELife. eLife
Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.
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,” eLife, 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.”
ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848.
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: '13356'
abstract:
- lang: eng
text: 'Self-assembly of nanoparticles can be mediated by polymers, but has so far
led almost exclusively to nanoparticle aggregates that are amorphous. Here, we
employed Coulombic interactions to generate a range of composite materials from
mixtures of charged nanoparticles and oppositely charged polymers. The assembly
behavior of these nanoparticle/polymer composites depends on their order of addition:
polymers added to nanoparticles give rise to stable aggregates, but nanoparticles
added to polymers disassemble the initially formed aggregates. The amorphous aggregates
were transformed into crystalline ones by transiently increasing the ionic strength
of the solution. The morphology of the resulting crystals depended on the length
of the polymer: short polymer chains mediated the self-assembly of nanoparticles
into strongly faceted crystals, whereas long chains led to pseudospherical nanoparticle/polymer
assemblies, within which the crystalline order of nanoparticles was retained.'
article_processing_charge: No
article_type: original
author:
- first_name: Tong
full_name: Bian, Tong
last_name: Bian
- first_name: Rafal
full_name: Klajn, Rafal
id: 8e84690e-1e48-11ed-a02b-a1e6fb8bb53b
last_name: Klajn
citation:
ama: Bian T, Klajn R. Morphology control in crystalline nanoparticle–polymer aggregates.
Annals of the New York Academy of Sciences. 2021;1505(1):191-201. doi:10.1111/nyas.14674
apa: Bian, T., & Klajn, R. (2021). Morphology control in crystalline nanoparticle–polymer
aggregates. Annals of the New York Academy of Sciences. Wiley. https://doi.org/10.1111/nyas.14674
chicago: Bian, Tong, and Rafal Klajn. “Morphology Control in Crystalline Nanoparticle–Polymer
Aggregates.” Annals of the New York Academy of Sciences. Wiley, 2021. https://doi.org/10.1111/nyas.14674.
ieee: T. Bian and R. Klajn, “Morphology control in crystalline nanoparticle–polymer
aggregates,” Annals of the New York Academy of Sciences, vol. 1505, no.
1. Wiley, pp. 191–201, 2021.
ista: Bian T, Klajn R. 2021. Morphology control in crystalline nanoparticle–polymer
aggregates. Annals of the New York Academy of Sciences. 1505(1), 191–201.
mla: Bian, Tong, and Rafal Klajn. “Morphology Control in Crystalline Nanoparticle–Polymer
Aggregates.” Annals of the New York Academy of Sciences, vol. 1505, no.
1, Wiley, 2021, pp. 191–201, doi:10.1111/nyas.14674.
short: T. Bian, R. Klajn, Annals of the New York Academy of Sciences 1505 (2021)
191–201.
date_created: 2023-08-01T09:33:39Z
date_published: 2021-12-01T00:00:00Z
date_updated: 2023-08-07T10:01:10Z
day: '01'
ddc:
- '540'
doi: 10.1111/nyas.14674
extern: '1'
external_id:
pmid:
- '34427923'
intvolume: ' 1505'
issue: '1'
keyword:
- History and Philosophy of Science
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1111/nyas.14674
month: '12'
oa: 1
oa_version: Published Version
page: 191-201
pmid: 1
publication: Annals of the New York Academy of Sciences
publication_identifier:
eissn:
- 1749-6632
issn:
- 0077-8923
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Morphology control in crystalline nanoparticle–polymer aggregates
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1505
year: '2021'
...
---
_id: '9073'
abstract:
- lang: eng
text: The sensory and cognitive abilities of the mammalian neocortex are underpinned
by intricate columnar and laminar circuits formed from an array of diverse neuronal
populations. One approach to determining how interactions between these circuit
components give rise to complex behavior is to investigate the rules by which
cortical circuits are formed and acquire functionality during development. This
review summarizes recent research on the development of the neocortex, from genetic
determination in neural stem cells through to the dynamic role that specific neuronal
populations play in the earliest circuits of neocortex, and how they contribute
to emergent function and cognition. While many of these endeavors take advantage
of model systems, consideration will also be given to advances in our understanding
of activity in nascent human circuits. Such cross-species perspective is imperative
when investigating the mechanisms underlying the dysfunction of early neocortical
circuits in neurodevelopmental disorders, so that one can identify targets amenable
to therapeutic intervention.
acknowledgement: Work in the I.L.H.-O. laboratory was supported by European Research
Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1,
Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported
by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical
Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and
102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by
European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This
work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G.
Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons
Foundation SFARI Research Award, and National Institutes of Health/National Institute
of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported
by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National
Institutes of Health, National Institute of General Medical Sciences R01GM134363-01,
and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the
University of California San Diego School of Medicine.
article_processing_charge: No
article_type: original
author:
- first_name: Ileana L.
full_name: Hanganu-Opatz, Ileana L.
last_name: Hanganu-Opatz
- first_name: Simon J. B.
full_name: Butt, Simon J. B.
last_name: Butt
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Natalia V.
full_name: De Marco García, Natalia V.
last_name: De Marco García
- first_name: Jessica A.
full_name: Cardin, Jessica A.
last_name: Cardin
- first_name: Bradley
full_name: Voytek, Bradley
last_name: Voytek
- first_name: Alysson R.
full_name: Muotri, Alysson R.
last_name: Muotri
citation:
ama: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical
circuits in health and disease. The Journal of Neuroscience. 2021;41(5):813-822.
doi:10.1523/jneurosci.1655-20.2020
apa: Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N.
V., Cardin, J. A., Voytek, B., & Muotri, A. R. (2021). The logic of developing
neocortical circuits in health and disease. The Journal of Neuroscience.
Society for Neuroscience. https://doi.org/10.1523/jneurosci.1655-20.2020
chicago: Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia
V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri.
“The Logic of Developing Neocortical Circuits in Health and Disease.” The Journal
of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/jneurosci.1655-20.2020.
ieee: I. L. Hanganu-Opatz et al., “The logic of developing neocortical circuits
in health and disease,” The Journal of Neuroscience, vol. 41, no. 5. Society
for Neuroscience, pp. 813–822, 2021.
ista: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA,
Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health
and disease. The Journal of Neuroscience. 41(5), 813–822.
mla: Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits
in Health and Disease.” The Journal of Neuroscience, vol. 41, no. 5, Society
for Neuroscience, 2021, pp. 813–22, doi:10.1523/jneurosci.1655-20.2020.
short: I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A.
Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.
date_created: 2021-02-03T12:23:51Z
date_published: 2021-02-03T00:00:00Z
date_updated: 2023-09-05T14:03:17Z
day: '03'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1523/jneurosci.1655-20.2020
ec_funded: 1
external_id:
isi:
- '000616763400002'
pmid:
- '33431633'
file:
- access_level: open_access
checksum: 578fd7ed1a0aef74bce61bea2d987b33
content_type: application/pdf
creator: dernst
date_created: 2022-05-27T06:59:55Z
date_updated: 2022-05-27T06:59:55Z
file_id: '11414'
file_name: 2021_JourNeuroscience_Hanganu.pdf
file_size: 1031150
relation: main_file
success: 1
file_date_updated: 2022-05-27T06:59:55Z
has_accepted_license: '1'
intvolume: ' 41'
isi: 1
issue: '5'
keyword:
- General Neuroscience
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 813-822
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: The Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: The logic of developing neocortical circuits in health and disease
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 41
year: '2021'
...
---
_id: '10301'
abstract:
- lang: eng
text: De novo protein synthesis is required for synapse modifications underlying
stable memory encoding. Yet neurons are highly compartmentalized cells and how
protein synthesis can be regulated at the synapse level is unknown. Here, we characterize
neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic
target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to
mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A
subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR
complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR
activation and restricts the mTOR-dependent translation of specific activity-regulated
mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent
protein synthesis, and facilitates the consolidation of associative and spatial
memories in mice. The memory enhancement becomes evident with light or spaced
training, can be achieved by selectively deleting GluN3A from excitatory neurons
during adulthood, and does not compromise other aspects of cognition such as memory
flexibility or extinction. Our findings provide mechanistic insight into synaptic
translational control and reveal a potentially selective target for cognitive
enhancement.
acknowledgement: We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a
knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral
and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and
Ana Navarro for expert technical help. Work was funded by the UTE project CIMA;
fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO
(to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.),
FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.);
ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program
RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077
FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637)
and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator
Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R),
Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence
Awards (SEV-2013-0317, SEV-2017-0723).
article_number: e71575
article_processing_charge: No
article_type: original
author:
- first_name: María J
full_name: Conde-Dusman, María J
last_name: Conde-Dusman
- first_name: Partha N
full_name: Dey, Partha N
last_name: Dey
- first_name: Óscar
full_name: Elía-Zudaire, Óscar
last_name: Elía-Zudaire
- first_name: Luis E
full_name: Garcia Rabaneda, Luis E
id: 33D1B084-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Rabaneda
- first_name: Carmen
full_name: García-Lira, Carmen
last_name: García-Lira
- first_name: Teddy
full_name: Grand, Teddy
last_name: Grand
- first_name: Victor
full_name: Briz, Victor
last_name: Briz
- first_name: Eric R
full_name: Velasco, Eric R
last_name: Velasco
- first_name: Raül
full_name: Andero Galí, Raül
last_name: Andero Galí
- first_name: Sergio
full_name: Niñerola, Sergio
last_name: Niñerola
- first_name: Angel
full_name: Barco, Angel
last_name: Barco
- first_name: Pierre
full_name: Paoletti, Pierre
last_name: Paoletti
- first_name: John F
full_name: Wesseling, John F
last_name: Wesseling
- first_name: Fabrizio
full_name: Gardoni, Fabrizio
last_name: Gardoni
- first_name: Steven J
full_name: Tavalin, Steven J
last_name: Tavalin
- first_name: Isabel
full_name: Perez-Otaño, Isabel
last_name: Perez-Otaño
citation:
ama: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
eLife. 2021;10. doi:10.7554/elife.71575
apa: Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E.,
García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575
chicago: Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia
Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein
Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1
Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.
ieee: M. J. Conde-Dusman et al., “Control of protein synthesis and memory
by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C,
Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling
JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and
memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife.
10, e71575.
mla: Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by
GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife,
vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.
short: M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira,
T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti,
J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).
date_created: 2021-11-18T06:59:45Z
date_published: 2021-11-17T00:00:00Z
date_updated: 2023-08-14T11:50:50Z
day: '17'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.7554/elife.71575
external_id:
isi:
- '000720945900001'
file:
- access_level: open_access
checksum: 59318e9e41507cec83c2f4070e6ad540
content_type: application/pdf
creator: lgarciar
date_created: 2021-11-18T07:02:02Z
date_updated: 2021-11-18T07:02:02Z
file_id: '10302'
file_name: elife-71575-v1.pdf
file_size: 2477302
relation: main_file
success: 1
file_date_updated: 2021-11-18T07:02:02Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- general immunology and microbiology
- general biochemistry
- genetics and molecular biology
- general medicine
- general neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
status: public
title: Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition
of GIT1/mTORC1 assembly
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: '11054'
abstract:
- lang: eng
text: In recent years, the nuclear pore complex (NPC) has emerged as a key player
in genome regulation and cellular homeostasis. New discoveries have revealed that
the NPC has multiple cellular functions besides mediating the molecular exchange
between the nucleus and the cytoplasm. In this review, we discuss non-transport
aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity
of the NPC proteins, and NPC dysfunction in age-related diseases. The examples
summarized herein demonstrate that the NPC, which first evolved to enable the
biochemical communication between the nucleus and the cytoplasm, now doubles as
the gatekeeper of cellular identity and aging.
article_processing_charge: No
article_type: review
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. Nuclear periphery takes center stage: The role of nuclear
pore complexes in cell identity and aging. Neuron. 2020;106(6):899-911.
doi:10.1016/j.neuron.2020.05.031'
apa: 'Cho, U. H., & Hetzer, M. (2020). Nuclear periphery takes center stage:
The role of nuclear pore complexes in cell identity and aging. Neuron.
Elsevier. https://doi.org/10.1016/j.neuron.2020.05.031'
chicago: 'Cho, Ukrae H., and Martin Hetzer. “Nuclear Periphery Takes Center Stage:
The Role of Nuclear Pore Complexes in Cell Identity and Aging.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.05.031.'
ieee: 'U. H. Cho and M. Hetzer, “Nuclear periphery takes center stage: The role
of nuclear pore complexes in cell identity and aging,” Neuron, vol. 106,
no. 6. Elsevier, pp. 899–911, 2020.'
ista: 'Cho UH, Hetzer M. 2020. Nuclear periphery takes center stage: The role of
nuclear pore complexes in cell identity and aging. Neuron. 106(6), 899–911.'
mla: 'Cho, Ukrae H., and Martin Hetzer. “Nuclear Periphery Takes Center Stage: The
Role of Nuclear Pore Complexes in Cell Identity and Aging.” Neuron, vol.
106, no. 6, Elsevier, 2020, pp. 899–911, doi:10.1016/j.neuron.2020.05.031.'
short: U.H. Cho, M. Hetzer, Neuron 106 (2020) 899–911.
date_created: 2022-04-07T07:43:36Z
date_published: 2020-06-17T00:00:00Z
date_updated: 2022-07-18T08:29:35Z
day: '17'
doi: 10.1016/j.neuron.2020.05.031
extern: '1'
external_id:
pmid:
- '32553207'
intvolume: ' 106'
issue: '6'
keyword:
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.neuron.2020.05.031
month: '06'
oa: 1
oa_version: Published Version
page: 899-911
pmid: 1
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Nuclear periphery takes center stage: The role of nuclear pore complexes in
cell identity and aging'
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 106
year: '2020'
...
---
_id: '11055'
abstract:
- lang: eng
text: Vascular dysfunctions are a common feature of multiple age-related diseases.
However, modeling healthy and pathological aging of the human vasculature represents
an unresolved experimental challenge. Here, we generated induced vascular endothelial
cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy
human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria
Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation
of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial
junction stability, as vascular aging markers. A functional assay performed on
PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that
iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which
plays a key role in both vascular calcification and endothelial barrier damage
observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS
vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered
the functionality of the vascular barrier in vitro, hence representing a potential
future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These
results show that iVECs and iSMCs retain disease-related signatures, allowing
modeling of vascular aging and HGPS in vitro.
article_number: e54383
article_processing_charge: No
article_type: original
author:
- first_name: Simone
full_name: Bersini, Simone
last_name: Bersini
- first_name: Roberta
full_name: Schulte, Roberta
last_name: Schulte
- first_name: Ling
full_name: Huang, Ling
last_name: Huang
- first_name: Hannah
full_name: Tsai, Hannah
last_name: Tsai
- 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: Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. Direct reprogramming of human
smooth muscle and vascular endothelial cells reveals defects associated with aging
and Hutchinson-Gilford progeria syndrome. eLife. 2020;9. doi:10.7554/elife.54383
apa: Bersini, S., Schulte, R., Huang, L., Tsai, H., & Hetzer, M. (2020). Direct
reprogramming of human smooth muscle and vascular endothelial cells reveals defects
associated with aging and Hutchinson-Gilford progeria syndrome. ELife.
eLife Sciences Publications. https://doi.org/10.7554/elife.54383
chicago: Bersini, Simone, Roberta Schulte, Ling Huang, Hannah Tsai, and Martin Hetzer.
“Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals
Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” ELife.
eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.54383.
ieee: S. Bersini, R. Schulte, L. Huang, H. Tsai, and M. Hetzer, “Direct reprogramming
of human smooth muscle and vascular endothelial cells reveals defects associated
with aging and Hutchinson-Gilford progeria syndrome,” eLife, vol. 9. eLife
Sciences Publications, 2020.
ista: Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. 2020. Direct reprogramming
of human smooth muscle and vascular endothelial cells reveals defects associated
with aging and Hutchinson-Gilford progeria syndrome. eLife. 9, e54383.
mla: Bersini, Simone, et al. “Direct Reprogramming of Human Smooth Muscle and Vascular
Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford
Progeria Syndrome.” ELife, vol. 9, e54383, eLife Sciences Publications,
2020, doi:10.7554/elife.54383.
short: S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020).
date_created: 2022-04-07T07:43:48Z
date_published: 2020-09-08T00:00:00Z
date_updated: 2022-07-18T08:30:37Z
day: '08'
ddc:
- '570'
doi: 10.7554/elife.54383
extern: '1'
external_id:
pmid:
- '32896271'
file:
- access_level: open_access
checksum: f8b3821349a194050be02570d8fe7d4b
content_type: application/pdf
creator: dernst
date_created: 2022-04-08T06:53:10Z
date_updated: 2022-04-08T06:53:10Z
file_id: '11132'
file_name: 2020_eLife_Bersini.pdf
file_size: 4399825
relation: main_file
success: 1
file_date_updated: 2022-04-08T06:53:10Z
has_accepted_license: '1'
intvolume: ' 9'
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
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Direct reprogramming of human smooth muscle and vascular endothelial cells
reveals defects associated with aging and Hutchinson-Gilford progeria syndrome
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: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 9
year: '2020'
...
---
_id: '11060'
abstract:
- lang: eng
text: The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum
(ER) that is gated by the nuclear pore complex. It is unknown whether proteins
of the INM and ER are degraded through shared or distinct pathways in mammalian
cells. We applied dynamic proteomics to profile protein half-lives and report
that INM and ER residents turn over at similar rates, indicating that the INM’s
unique topology is not a barrier to turnover. Using a microscopy approach, we
observed that the proteasome can degrade INM proteins in situ. However, we also
uncovered evidence for selective, vesicular transport-mediated turnover of a single
INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared
from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular
trafficking to lysosomes. This work demonstrates that the INM can be dynamically
remodeled in response to environmental inputs.
article_number: e49796
article_processing_charge: No
article_type: original
author:
- first_name: Abigail
full_name: Buchwalter, Abigail
last_name: Buchwalter
- first_name: Roberta
full_name: Schulte, Roberta
last_name: Schulte
- first_name: Hsiao
full_name: Tsai, Hsiao
last_name: Tsai
- first_name: Juliana
full_name: Capitanio, Juliana
last_name: Capitanio
- 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: Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. Selective clearance
of the inner nuclear membrane protein emerin by vesicular transport during ER
stress. eLife. 2019;8. doi:10.7554/elife.49796
apa: Buchwalter, A., Schulte, R., Tsai, H., Capitanio, J., & Hetzer, M. (2019).
Selective clearance of the inner nuclear membrane protein emerin by vesicular
transport during ER stress. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.49796
chicago: Buchwalter, Abigail, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, and
Martin Hetzer. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin
by Vesicular Transport during ER Stress.” ELife. eLife Sciences Publications,
2019. https://doi.org/10.7554/elife.49796.
ieee: A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, and M. Hetzer, “Selective
clearance of the inner nuclear membrane protein emerin by vesicular transport
during ER stress,” eLife, vol. 8. eLife Sciences Publications, 2019.
ista: Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. 2019. Selective clearance
of the inner nuclear membrane protein emerin by vesicular transport during ER
stress. eLife. 8, e49796.
mla: Buchwalter, Abigail, et al. “Selective Clearance of the Inner Nuclear Membrane
Protein Emerin by Vesicular Transport during ER Stress.” ELife, vol. 8,
e49796, eLife Sciences Publications, 2019, doi:10.7554/elife.49796.
short: A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, M. Hetzer, ELife 8 (2019).
date_created: 2022-04-07T07:45:02Z
date_published: 2019-10-10T00:00:00Z
date_updated: 2023-05-31T06:36:22Z
day: '10'
ddc:
- '570'
doi: 10.7554/elife.49796
extern: '1'
external_id:
pmid:
- '31599721'
file:
- access_level: open_access
checksum: 1e8672a1e9c3dc0a2d3d0dad89673616
content_type: application/pdf
creator: dernst
date_created: 2022-04-08T08:18:01Z
date_updated: 2022-04-08T08:18:01Z
file_id: '11138'
file_name: 2019_eLife_Buchwalter.pdf
file_size: 6984654
relation: main_file
success: 1
file_date_updated: 2022-04-08T08:18:01Z
has_accepted_license: '1'
intvolume: ' 8'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '13079'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Selective clearance of the inner nuclear membrane protein emerin by vesicular
transport during ER 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: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 8
year: '2019'
...
---
_id: '12192'
abstract:
- lang: eng
text: Transposable elements (TEs), the movement of which can damage the genome,
are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in
the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis
thaliana. However, the extent and mechanism of this activation are unknown. Here
we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed
DNA demethylation. We further demonstrate that DEMETER access to some of these
TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically
expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent
mechanism. We demonstrate that H1 is required for heterochromatin condensation
in plant cells and show that H1 overexpression creates heterochromatic foci in
the VC progenitor cell. Taken together, our results demonstrate that the natural
depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation,
heterochromatin relaxation, and TE activation.
acknowledgement: We thank David Twell for the pDONR-P4-P1R-pLAT52 and pDONR-P2R-P3-mRFP
vectors, the John Innes Centre Bioimaging Facility (Elaine Barclay and Grant Calder)
for their assistance with microscopy, and the Norwich BioScience Institute Partnership
Computing infrastructure for Science Group for High Performance Computing resources.
This work was funded by a Biotechnology and Biological Sciences Research Council
(BBSRC) David Phillips Fellowship (BB/L025043/1; SH, JZ and XF), a European Research
Council Starting Grant ('SexMeth' 804981; XF) and a Grant to Exceptional Researchers
by the Gatsby Charitable Foundation (SH and XF).
article_number: '42530'
article_processing_charge: No
article_type: original
author:
- first_name: Shengbo
full_name: He, Shengbo
last_name: He
- first_name: Martin
full_name: Vickers, Martin
last_name: Vickers
- first_name: Jingyi
full_name: Zhang, Jingyi
last_name: Zhang
- first_name: Xiaoqi
full_name: Feng, Xiaoqi
id: e0164712-22ee-11ed-b12a-d80fcdf35958
last_name: Feng
orcid: 0000-0002-4008-1234
citation:
ama: He S, Vickers M, Zhang J, Feng X. Natural depletion of histone H1 in sex cells
causes DNA demethylation, heterochromatin decondensation and transposon activation.
eLife. 2019;8. doi:10.7554/elife.42530
apa: He, S., Vickers, M., Zhang, J., & Feng, X. (2019). Natural depletion of
histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation
and transposon activation. ELife. eLife Sciences Publications, Ltd. https://doi.org/10.7554/elife.42530
chicago: He, Shengbo, Martin Vickers, Jingyi Zhang, and Xiaoqi Feng. “Natural Depletion
of Histone H1 in Sex Cells Causes DNA Demethylation, Heterochromatin Decondensation
and Transposon Activation.” ELife. eLife Sciences Publications, Ltd, 2019.
https://doi.org/10.7554/elife.42530.
ieee: S. He, M. Vickers, J. Zhang, and X. Feng, “Natural depletion of histone H1
in sex cells causes DNA demethylation, heterochromatin decondensation and transposon
activation,” eLife, vol. 8. eLife Sciences Publications, Ltd, 2019.
ista: He S, Vickers M, Zhang J, Feng X. 2019. Natural depletion of histone H1 in
sex cells causes DNA demethylation, heterochromatin decondensation and transposon
activation. eLife. 8, 42530.
mla: He, Shengbo, et al. “Natural Depletion of Histone H1 in Sex Cells Causes DNA
Demethylation, Heterochromatin Decondensation and Transposon Activation.” ELife,
vol. 8, 42530, eLife Sciences Publications, Ltd, 2019, doi:10.7554/elife.42530.
short: S. He, M. Vickers, J. Zhang, X. Feng, ELife 8 (2019).
date_created: 2023-01-16T09:17:21Z
date_published: 2019-05-28T00:00:00Z
date_updated: 2023-05-08T10:54:12Z
day: '28'
ddc:
- '580'
department:
- _id: XiFe
doi: 10.7554/elife.42530
extern: '1'
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- '31135340'
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intvolume: ' 8'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594752/
month: '05'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications, Ltd
quality_controlled: '1'
scopus_import: '1'
status: public
title: Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin
decondensation and transposon activation
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: 8
year: '2019'
...
---
_id: '10370'
abstract:
- lang: eng
text: Eukaryotic cells are densely packed with macromolecular complexes and intertwining
organelles, continually transported and reshaped. Intriguingly, organelles avoid
clashing and entangling with each other in such limited space. Mitochondria form
extensive networks constantly remodeled by fission and fusion. Here, we show that
mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of
mitochondria – via encounter with motile intracellular pathogens, via external
pressure applied by an atomic force microscope, or via cell migration across uneven
microsurfaces – results in the recruitment of the mitochondrial fission machinery,
and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria,
acts as a membrane-bound force sensor to recruit the fission machinery to mechanically
strained sites. Thus, mitochondria adapt to the environment by sensing and responding
to biomechanical cues. Our findings that mechanical triggers can be coupled to
biochemical responses in membrane dynamics may explain how organelles orderly
cohabit in the crowded cytoplasm.
article_number: e30292
article_processing_charge: No
article_type: original
author:
- first_name: Sebastian Carsten Johannes
full_name: Helle, Sebastian Carsten Johannes
last_name: Helle
- first_name: Qian
full_name: Feng, Qian
last_name: Feng
- first_name: Mathias J
full_name: Aebersold, Mathias J
last_name: Aebersold
- first_name: Luca
full_name: Hirt, Luca
last_name: Hirt
- first_name: Raphael R
full_name: Grüter, Raphael R
last_name: Grüter
- first_name: Afshin
full_name: Vahid, Afshin
last_name: Vahid
- first_name: Andrea
full_name: Sirianni, Andrea
last_name: Sirianni
- first_name: Serge
full_name: Mostowy, Serge
last_name: Mostowy
- first_name: Jess G
full_name: Snedeker, Jess G
last_name: Snedeker
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Timon
full_name: Idema, Timon
last_name: Idema
- first_name: Tomaso
full_name: Zambelli, Tomaso
last_name: Zambelli
- first_name: Benoît
full_name: Kornmann, Benoît
last_name: Kornmann
citation:
ama: Helle SCJ, Feng Q, Aebersold MJ, et al. Mechanical force induces mitochondrial
fission. eLife. 2017;6. doi:10.7554/elife.30292
apa: Helle, S. C. J., Feng, Q., Aebersold, M. J., Hirt, L., Grüter, R. R., Vahid,
A., … Kornmann, B. (2017). Mechanical force induces mitochondrial fission. ELife.
eLife Sciences Publications. https://doi.org/10.7554/elife.30292
chicago: Helle, Sebastian Carsten Johannes, Qian Feng, Mathias J Aebersold, Luca
Hirt, Raphael R Grüter, Afshin Vahid, Andrea Sirianni, et al. “Mechanical Force
Induces Mitochondrial Fission.” ELife. eLife Sciences Publications, 2017.
https://doi.org/10.7554/elife.30292.
ieee: S. C. J. Helle et al., “Mechanical force induces mitochondrial fission,”
eLife, vol. 6. eLife Sciences Publications, 2017.
ista: Helle SCJ, Feng Q, Aebersold MJ, Hirt L, Grüter RR, Vahid A, Sirianni A, Mostowy
S, Snedeker JG, Šarić A, Idema T, Zambelli T, Kornmann B. 2017. Mechanical force
induces mitochondrial fission. eLife. 6, e30292.
mla: Helle, Sebastian Carsten Johannes, et al. “Mechanical Force Induces Mitochondrial
Fission.” ELife, vol. 6, e30292, eLife Sciences Publications, 2017, doi:10.7554/elife.30292.
short: S.C.J. Helle, Q. Feng, M.J. Aebersold, L. Hirt, R.R. Grüter, A. Vahid, A.
Sirianni, S. Mostowy, J.G. Snedeker, A. Šarić, T. Idema, T. Zambelli, B. Kornmann,
ELife 6 (2017).
date_created: 2021-11-29T08:51:38Z
date_published: 2017-11-09T00:00:00Z
date_updated: 2021-11-29T09:28:14Z
day: '09'
ddc:
- '572'
doi: 10.7554/elife.30292
extern: '1'
external_id:
pmid:
- '29119945'
file:
- access_level: open_access
checksum: c35f42dcfb007f6d6c761a27e24c26d3
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-29T09:07:41Z
date_updated: 2021-11-29T09:07:41Z
file_id: '10372'
file_name: 2017_eLife_Helle.pdf
file_size: 6120157
relation: main_file
success: 1
file_date_updated: 2021-11-29T09:07:41Z
has_accepted_license: '1'
intvolume: ' 6'
keyword:
- general immunology and microbiology
- general biochemistry
- genetics and molecular biology
- general medicine
- general neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://elifesciences.org/articles/30292
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanical force induces mitochondrial fission
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'
...