2024-03-29T10:44:14Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/2370532019-08-30T11:28:51Zcom_10033_620659col_10033_620660
Fava, E
35a15dd1c097fb6511eee2659e812875
500
Dehghany, J
4a4d062adc9ade8d5ddf834e0f24497b
500
Ouwendijk, J
be6321585e01ccbc7ab9bfc681ebd03f
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Niederlein, A
35fb431bcb3487767bee96e960921ade
500
Verkade, P
d745061be8d1746e69b49f6cd82f9273
500
Meyer-Hermann, M
b1629cdd476ccc6fa145c74ad4644921
500
Solimena, M
1b346312c5ee49f78c3f9411500d2825
500
Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
2012-08-02T13:06:00Z
2012-08-02T13:06:00Z
2012-04
Novel standards in the measurement of rat insulin granules combining electron microscopy, high-content image analysis and in silico modelling. 2012, 55 (4):1013-23 Diabetologia
1432-0428
22252472
10.1007/s00125-011-2438-4
http://hdl.handle.net/10033/237053
Diabetologia
Knowledge of number, size and content of insulin secretory granules is pivotal for understanding the physiology of pancreatic beta cells. Here we re-evaluated key structural features of rat beta cells, including insulin granule size, number and distribution as well as cell size.
en
Archived with thanks to Diabetologia
Novel standards in the measurement of rat insulin granules combining electron microscopy, high-content image analysis and in silico modelling.
Article
2018-06-13T00:56:38Z
Knowledge of number, size and content of insulin secretory granules is pivotal for understanding the physiology of pancreatic beta cells. Here we re-evaluated key structural features of rat beta cells, including insulin granule size, number and distribution as well as cell size.
ORIGINAL
Fava et al_final.pdf
Fava et al_final.pdf
Open Access document
application/pdf
727860
https://hzi.openrepository.com/bitstream/10033/237053/1/Fava%20et%20al_final.pdf
165382d6b0ba2bf1ae5901367b219c36
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/237053/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/237053/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/237053/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/237053/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Fava et al_final.pdf.txt
Fava et al_final.pdf.txt
Extracted Text
text/plain
43817
https://hzi.openrepository.com/bitstream/10033/237053/8/Fava%20et%20al_final.pdf.txt
d31d98d6b3fb4571c3a90257635645c8
MD5
8
false
THUMBNAIL
Fava et al_final.pdf.jpg
Fava et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
31071
https://hzi.openrepository.com/bitstream/10033/237053/9/Fava%20et%20al_final.pdf.jpg
80eb360945628821ef8360ddf0b1bdb3
MD5
9
false
10033/237053
oai:hzi.openrepository.com:10033/237053
2019-08-30 11:28:51.357
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/2461512019-08-30T11:31:23Zcom_10033_620659col_10033_620660
Figge, Marc Thilo
2629fa1216f053aba173458a782dd99f
500
Reichert, Andreas S
615fb2807e8a75dabd0c661b6d6b09c3
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Osiewacz, Heinz D
f0a3c7a1aefdb8d88fe14bc29f5ebf0b
500
Applied Systems Biology, Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute and Friedrich Schiller University, Jena, Germany.
2012-09-27T12:32:19Z
2012-09-27T12:32:19Z
2012-06
Deceleration of fusion-fission cycles improves mitochondrial quality control during aging. 2012, 8 (6):e1002576 PLoS Comput. Biol.
1553-7358
22761564
10.1371/journal.pcbi.1002576
http://hdl.handle.net/10033/246151
PLoS computational biology
Mitochondrial dynamics and mitophagy play a key role in ensuring mitochondrial quality control. Impairment thereof was proposed to be causative to neurodegenerative diseases, diabetes, and cancer. Accumulation of mitochondrial dysfunction was further linked to aging. Here we applied a probabilistic modeling approach integrating our current knowledge on mitochondrial biology allowing us to simulate mitochondrial function and quality control during aging in silico. We demonstrate that cycles of fusion and fission and mitophagy indeed are essential for ensuring a high average quality of mitochondria, even under conditions in which random molecular damage is present. Prompted by earlier observations that mitochondrial fission itself can cause a partial drop in mitochondrial membrane potential, we tested the consequences of mitochondrial dynamics being harmful on its own. Next to directly impairing mitochondrial function, pre-existing molecular damage may be propagated and enhanced across the mitochondrial population by content mixing. In this situation, such an infection-like phenomenon impairs mitochondrial quality control progressively. However, when imposing an age-dependent deceleration of cycles of fusion and fission, we observe a delay in the loss of average quality of mitochondria. This provides a rational why fusion and fission rates are reduced during aging and why loss of a mitochondrial fission factor can extend life span in fungi. We propose the 'mitochondrial infectious damage adaptation' (MIDA) model according to which a deceleration of fusion-fission cycles reflects a systemic adaptation increasing life span.
en
Archived with thanks to PLoS computational biology
Deceleration of fusion-fission cycles improves mitochondrial quality control during aging.
Article
2018-06-13T19:56:02Z
Mitochondrial dynamics and mitophagy play a key role in ensuring mitochondrial quality control. Impairment thereof was proposed to be causative to neurodegenerative diseases, diabetes, and cancer. Accumulation of mitochondrial dysfunction was further linked to aging. Here we applied a probabilistic modeling approach integrating our current knowledge on mitochondrial biology allowing us to simulate mitochondrial function and quality control during aging in silico. We demonstrate that cycles of fusion and fission and mitophagy indeed are essential for ensuring a high average quality of mitochondria, even under conditions in which random molecular damage is present. Prompted by earlier observations that mitochondrial fission itself can cause a partial drop in mitochondrial membrane potential, we tested the consequences of mitochondrial dynamics being harmful on its own. Next to directly impairing mitochondrial function, pre-existing molecular damage may be propagated and enhanced across the mitochondrial population by content mixing. In this situation, such an infection-like phenomenon impairs mitochondrial quality control progressively. However, when imposing an age-dependent deceleration of cycles of fusion and fission, we observe a delay in the loss of average quality of mitochondria. This provides a rational why fusion and fission rates are reduced during aging and why loss of a mitochondrial fission factor can extend life span in fungi. We propose the 'mitochondrial infectious damage adaptation' (MIDA) model according to which a deceleration of fusion-fission cycles reflects a systemic adaptation increasing life span.
ORIGINAL
Figge et al_final.pdf
Figge et al_final.pdf
Open Access publication
application/pdf
1195831
https://hzi.openrepository.com/bitstream/10033/246151/1/Figge%20et%20al_final.pdf
370ca1c775d7d5ed4a818e52195305b3
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/246151/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/246151/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/246151/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/246151/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Figge et al_final.pdf.txt
Figge et al_final.pdf.txt
Extracted Text
text/plain
95249
https://hzi.openrepository.com/bitstream/10033/246151/8/Figge%20et%20al_final.pdf.txt
9e672242bd609b70e7f4224cb192a6bf
MD5
8
false
THUMBNAIL
Figge et al_final.pdf.jpg
Figge et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
29316
https://hzi.openrepository.com/bitstream/10033/246151/9/Figge%20et%20al_final.pdf.jpg
48833913aeb5f7217ad44ce39aa25b42
MD5
9
false
10033/246151
oai:hzi.openrepository.com:10033/246151
2019-08-30 11:31:23.677
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/2488222019-08-30T11:31:18Zcom_10033_620659col_10033_620660
Dustin, Michael L
ac13dfbdd962c435ae8154c76ebb5bd1
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Skirball Institute for Molecular Medicine, New York University School of Medicine, New York, NY 10016, USA. michael.dustin@med.nyu.edu
2012-10-15T14:36:42Z
2012-10-15T14:36:42Z
2012-01-27
Immunology. Antigen feast or famine. 2012, 335 (6067):408-9 Science
1095-9203
22282794
10.1126/science.1218165
http://hdl.handle.net/10033/248822
Science (New York, N.Y.)
en
Archived with thanks to Science (New York, N.Y.)
Animals
Antigen Presentation
Antigens
B-Lymphocytes
Lymphocyte Activation
T-Lymphocytes
Immunology. Antigen feast or famine.
Article
2018-06-12T23:54:32Z
ORIGINAL
Dustin & Meyer-Hermann_final.pdf
Dustin & Meyer-Hermann_final.pdf
original manuscript
application/pdf
152838
https://hzi.openrepository.com/bitstream/10033/248822/1/Dustin%20%26%20Meyer-Hermann_final.pdf
bf6582eec6b172073114b36a5212ef36
MD5
1
true
On line supplement.pdf
On line supplement.pdf
supplemental material
application/pdf
40861
https://hzi.openrepository.com/bitstream/10033/248822/2/On%20line%20supplement.pdf
fc10061a4bac5dd27b3fa47067d64444
MD5
2
false
Figures.pdf
Figures.pdf
figues
application/pdf
120684
https://hzi.openrepository.com/bitstream/10033/248822/3/Figures.pdf
f9c88e6c47b16a326c07b94502408a77
MD5
3
false
Supplemental figure_S1.pdf
Supplemental figure_S1.pdf
supplemental figure
application/pdf
335010
https://hzi.openrepository.com/bitstream/10033/248822/4/Supplemental%20figure_S1.pdf
4fd856b1cdd337226037500d02005769
MD5
4
false
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/248822/5/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
5
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/248822/6/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
6
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/248822/7/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
7
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/248822/8/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
8
false
TEXT
Dustin & Meyer-Hermann_final.pdf.txt
Dustin & Meyer-Hermann_final.pdf.txt
Extracted Text
text/plain
6984
https://hzi.openrepository.com/bitstream/10033/248822/17/Dustin%20%26%20Meyer-Hermann_final.pdf.txt
bd322920e8e9f684ee63214bdcfe1d47
MD5
17
false
Supplemental figure_S1.pdf.txt
Supplemental figure_S1.pdf.txt
Extracted Text
text/plain
1
https://hzi.openrepository.com/bitstream/10033/248822/18/Supplemental%20figure_S1.pdf.txt
58c89562f58fd276f592420068db8c09
MD5
18
false
Figures.pdf.txt
Figures.pdf.txt
Extracted Text
text/plain
106
https://hzi.openrepository.com/bitstream/10033/248822/19/Figures.pdf.txt
f0d06c1f708d321658fcd37c128c9551
MD5
19
false
On line supplement.pdf.txt
On line supplement.pdf.txt
Extracted Text
text/plain
6300
https://hzi.openrepository.com/bitstream/10033/248822/20/On%20line%20supplement.pdf.txt
a71f744a8a744e28dfbd2bbd4e80d007
MD5
20
false
THUMBNAIL
Dustin & Meyer-Hermann_final.pdf.jpg
Dustin & Meyer-Hermann_final.pdf.jpg
Generated Thumbnail
image/jpeg
22965
https://hzi.openrepository.com/bitstream/10033/248822/25/Dustin%20%26%20Meyer-Hermann_final.pdf.jpg
54e52503fb287eeff06469e0c9f69c91
MD5
25
false
On line supplement.pdf.jpg
On line supplement.pdf.jpg
Generated Thumbnail
image/jpeg
103191
https://hzi.openrepository.com/bitstream/10033/248822/26/On%20line%20supplement.pdf.jpg
852198eb12bb923c2a766d2c36e023d4
MD5
26
false
Figures.pdf.jpg
Figures.pdf.jpg
Generated Thumbnail
image/jpeg
27557
https://hzi.openrepository.com/bitstream/10033/248822/27/Figures.pdf.jpg
bdc83ef3c0eab07a5af6b72402655361
MD5
27
false
Supplemental figure_S1.pdf.jpg
Supplemental figure_S1.pdf.jpg
Generated Thumbnail
image/jpeg
26900
https://hzi.openrepository.com/bitstream/10033/248822/28/Supplemental%20figure_S1.pdf.jpg
15500dcfea6e148540905e34a51d7f5c
MD5
28
false
10033/248822
oai:hzi.openrepository.com:10033/248822
2019-08-30 11:31:18.543
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/2788922019-08-30T11:25:42Zcom_10033_620659col_10033_620660
Hernandez-Vargas, Esteban A.
51fcf49197545029cbb3be828e17add0
500
Colaneri, Patrizio
b9aed58ef94a5a896ba1327d02085a0f
500
Middleton, Richard H.
fc6240d45da0213e0b83a0a1f292798c
500
Helmholtz-Zentrum für Infektionsforschung-HZI, 39124 Braunschweig
2013-04-04T08:38:17Z
2013-04-04T08:38:17Z
2012-12-13
10.1109/CDC.2012.6426559
http://hdl.handle.net/10033/278892
IEEE Conference on Decision and Control
http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=6426559
Sub-optimal switching with dwell time constraints for control of viral mutation
Article
2018-06-13T17:06:51Z
ORIGINAL
Hernandez-Vargas et al_final.pdf
Hernandez-Vargas et al_final.pdf
Open Access publication
application/pdf
321629
https://hzi.openrepository.com/bitstream/10033/278892/1/Hernandez-Vargas%20et%20al_final.pdf
6ab80a444c750c21902512cfba1e237b
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/278892/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/278892/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/278892/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/278892/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Hernandez-Vargas et al_final.pdf.txt
Hernandez-Vargas et al_final.pdf.txt
Extracted Text
text/plain
28214
https://hzi.openrepository.com/bitstream/10033/278892/8/Hernandez-Vargas%20et%20al_final.pdf.txt
f1fa7ef4c826f2effafb6746a4b52ac7
MD5
8
false
THUMBNAIL
Hernandez-Vargas et al_final.pdf.jpg
Hernandez-Vargas et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
29646
https://hzi.openrepository.com/bitstream/10033/278892/9/Hernandez-Vargas%20et%20al_final.pdf.jpg
7bf99b60fb093c08121e7f762fd9d32d
MD5
9
false
10033/278892
oai:hzi.openrepository.com:10033/278892
2019-08-30 11:25:42.736
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/2813122019-08-30T11:33:05Zcom_10033_620659col_10033_620660
Hernandez-Vargas, Esteban A
f5f76475c898e2d172a51445be77c1ec
500
Middleton, Richard H
ece86142bd83813f3b8a0cd64e969b21
500
SIMM, Helmholtz Zentrum für Infektionsforschung, Inhoffenstraße 7, D-38124 Braunschweig, Germany.
2013-04-15T12:48:28Z
2013-04-15T12:48:28Z
2013-03-07
Modeling the three stages in HIV infection. 2013, 320:33-40 J. Theor. Biol.
1095-8541
23238280
10.1016/j.jtbi.2012.11.028
http://hdl.handle.net/10033/281312
Journal of theoretical biology
A typical HIV infection response consists of three stages: an initial acute infection, a long asymptomatic period and a final increase in viral load with simultaneous collapse in healthy CD4+T cell counts. The majority of existing mathematical models give a good representation of either the first two stages or the last stage of the infection. Using macrophages as a long-term active reservoir, a deterministic model is proposed to explain the three stages of the infection including the progression to AIDS. Simulation results illustrate how chronic infected macrophages can explain the progression to AIDS provoking viral explosion. Further simulation studies suggest that the proposed model retains its key properties even under moderately large parameter variations. This model provides important insights on how macrophages might play a crucial role in the long term behavior of HIV infection.
en
Archived with thanks to Journal of theoretical biology
Modeling the three stages in HIV infection.
Article
2018-06-12T22:15:53Z
A typical HIV infection response consists of three stages: an initial acute infection, a long asymptomatic period and a final increase in viral load with simultaneous collapse in healthy CD4+T cell counts. The majority of existing mathematical models give a good representation of either the first two stages or the last stage of the infection. Using macrophages as a long-term active reservoir, a deterministic model is proposed to explain the three stages of the infection including the progression to AIDS. Simulation results illustrate how chronic infected macrophages can explain the progression to AIDS provoking viral explosion. Further simulation studies suggest that the proposed model retains its key properties even under moderately large parameter variations. This model provides important insights on how macrophages might play a crucial role in the long term behavior of HIV infection.
ORIGINAL
Hernandez-Vargas_Middleton_final.pdf
Hernandez-Vargas_Middleton_final.pdf
original submission
application/pdf
1434688
https://hzi.openrepository.com/bitstream/10033/281312/1/Hernandez-Vargas_Middleton_final.pdf
99534c2289066d945fcc63f625530bb7
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/281312/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/281312/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/281312/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/281312/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Hernandez-Vargas_Middleton_final.pdf.txt
Hernandez-Vargas_Middleton_final.pdf.txt
Extracted Text
text/plain
39794
https://hzi.openrepository.com/bitstream/10033/281312/8/Hernandez-Vargas_Middleton_final.pdf.txt
e631295cb8f5808a367caea18373e18e
MD5
8
false
THUMBNAIL
Hernandez-Vargas_Middleton_final.pdf.jpg
Hernandez-Vargas_Middleton_final.pdf.jpg
Generated Thumbnail
image/jpeg
24553
https://hzi.openrepository.com/bitstream/10033/281312/9/Hernandez-Vargas_Middleton_final.pdf.jpg
0356ac6084e95c65a4028d495ce6e2ac
MD5
9
false
elsevier-thumbnail.png
application/octet-stream
121622
https://hzi.openrepository.com/bitstream/10033/281312/10/elsevier-thumbnail.png
21b258c399f3da5d39a6112fb24559cc
MD5
10
false
10033/281312
oai:hzi.openrepository.com:10033/281312
2019-08-30 11:33:05.424
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/2832122019-08-30T11:26:38Zcom_10033_620659col_10033_620660
Hernandez-Vargas, Esteban A.
51fcf49197545029cbb3be828e17add0
500
Alanis, Alma Y.
1ca556daf0c68cfd169b7c75bc24d4ed
500
Sanchez, Edgar N.
92a5f5a3e9e99d447dfac69a5701f0d9
500
Systems Immunology, Helmholtz-Zentrum für Infecktionsforschung, Inhoffenstraße 7, D-38124, Braunschweig, Germany
2013-04-19T12:30:01Z
2013-04-19T12:30:01Z
2013-04-19
978-1-4673-4497-5
http://hdl.handle.net/10033/283212
Institute of Electrical and Electronics Engineers
http://ieeexplore.ieee.org/xpl/articleDetails.jsp?tp=&arnumber=6320891&contentType=Conference+Publications&searchWithin%3Dp_Last_Names%3AHernandez-Vargas%26matchBoolean%3Dtrue%26queryText%3D%28p_Authors%3AHernandez-Vargas%29
Discrete-time neural observer for HIV infection dynamic
Meetings and Proceedings
2018-06-12T16:44:16Z
ORIGINAL
Hernandez-Vargas et al_final.pdf
Hernandez-Vargas et al_final.pdf
submitted manuscript
application/pdf
675602
https://hzi.openrepository.com/bitstream/10033/283212/1/Hernandez-Vargas%20et%20al_final.pdf
b39bfc223c6aebf3880f5db582c74afd
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/283212/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/283212/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/283212/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/283212/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Hernandez-Vargas et al_final.pdf.txt
Hernandez-Vargas et al_final.pdf.txt
Extracted Text
text/plain
22703
https://hzi.openrepository.com/bitstream/10033/283212/8/Hernandez-Vargas%20et%20al_final.pdf.txt
ad4e28a35723c009ddf658b4275b92f8
MD5
8
false
THUMBNAIL
Hernandez-Vargas et al_final.pdf.jpg
Hernandez-Vargas et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
27587
https://hzi.openrepository.com/bitstream/10033/283212/9/Hernandez-Vargas%20et%20al_final.pdf.jpg
c09497ce0d04d9f62965cdf018a86aae
MD5
9
false
10033/283212
oai:hzi.openrepository.com:10033/283212
2019-08-30 11:26:38.662
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/2911312019-08-30T11:32:17Zcom_10033_620659col_10033_620660
Binder, Sebastian C
5f59b1f232c7fd9dd584163b14e1b927
500
Telschow, Arndt
69f0aaab42cd7bedec61aceffbb6ba83
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Department of Systems Immunology, Helmholtz Centre for Infection Research Braunschweig, Germany.
2013-05-15T09:24:01Z
2013-05-15T09:24:01Z
2012
Population Dynamics of Borrelia burgdorferi in Lyme Disease. 2012, 3:104 Front Microbiol
1664-302X
22470370
10.3389/fmicb.2012.00104
http://hdl.handle.net/10033/291131
Frontiers in microbiology
Many chronic inflammatory diseases are known to be caused by persistent bacterial or viral infections. A well-studied example is the tick-borne infection by the gram-negative spirochaetes of the genus Borrelia in humans and other mammals, causing severe symptoms of chronic inflammation and subsequent tissue damage (Lyme Disease), particularly in large joints and the central nervous system, but also in the heart and other tissues of untreated patients. Although killed efficiently by human phagocytic cells in vitro, Borrelia exhibits a remarkably high infectivity in mice and men. In experimentally infected mice, the first immune response almost clears the infection. However, approximately 1 week post infection, the bacterial population recovers and reaches an even larger size before entering the chronic phase. We developed a mathematical model describing the bacterial growth and the immune response against Borrelia burgdorferi in the C3H mouse strain that has been established as an experimental model for Lyme disease. The peculiar dynamics of the infection exclude two possible mechanistic explanations for the regrowth of the almost cleared bacteria. Neither the hypothesis of bacterial dissemination to different tissues nor a limitation of phagocytic capacity were compatible with experiment. The mathematical model predicts that Borrelia recovers from the strong initial immune response by the regrowth of an immune-resistant sub-population of the bacteria. The chronic phase appears as an equilibration of bacterial growth and adaptive immunity. This result has major implications for the development of the chronic phase of Borrelia infections as well as on potential protective clinical interventions.
en
Archived with thanks to Frontiers in microbiology
Population Dynamics of Borrelia burgdorferi in Lyme Disease.
Article
2018-06-13T00:38:13Z
Many chronic inflammatory diseases are known to be caused by persistent bacterial or viral infections. A well-studied example is the tick-borne infection by the gram-negative spirochaetes of the genus Borrelia in humans and other mammals, causing severe symptoms of chronic inflammation and subsequent tissue damage (Lyme Disease), particularly in large joints and the central nervous system, but also in the heart and other tissues of untreated patients. Although killed efficiently by human phagocytic cells in vitro, Borrelia exhibits a remarkably high infectivity in mice and men. In experimentally infected mice, the first immune response almost clears the infection. However, approximately 1 week post infection, the bacterial population recovers and reaches an even larger size before entering the chronic phase. We developed a mathematical model describing the bacterial growth and the immune response against Borrelia burgdorferi in the C3H mouse strain that has been established as an experimental model for Lyme disease. The peculiar dynamics of the infection exclude two possible mechanistic explanations for the regrowth of the almost cleared bacteria. Neither the hypothesis of bacterial dissemination to different tissues nor a limitation of phagocytic capacity were compatible with experiment. The mathematical model predicts that Borrelia recovers from the strong initial immune response by the regrowth of an immune-resistant sub-population of the bacteria. The chronic phase appears as an equilibration of bacterial growth and adaptive immunity. This result has major implications for the development of the chronic phase of Borrelia infections as well as on potential protective clinical interventions.
ORIGINAL
Binder_final.pdf
Binder_final.pdf
Open Access publication
application/pdf
848779
https://hzi.openrepository.com/bitstream/10033/291131/1/Binder_final.pdf
5b5caf13a17e867033e244d04e4376fb
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/291131/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/291131/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/291131/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/291131/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Binder_final.pdf.txt
Binder_final.pdf.txt
Extracted Text
text/plain
54998
https://hzi.openrepository.com/bitstream/10033/291131/8/Binder_final.pdf.txt
a40d68276655ec0e6981e69675a6c849
MD5
8
false
THUMBNAIL
Binder_final.pdf.jpg
Binder_final.pdf.jpg
Generated Thumbnail
image/jpeg
26614
https://hzi.openrepository.com/bitstream/10033/291131/9/Binder_final.pdf.jpg
b78d311d105a2fdd5584ab934ea8908f
MD5
9
false
10033/291131
oai:hzi.openrepository.com:10033/291131
2019-08-30 11:32:17.04
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3046622019-08-30T11:29:47Zcom_10033_620659col_10033_620660
Schmeitz, Christine
9891ef0fddcdd30dcbb6f784197dbd79
500
Hernandez-Vargas, Esteban Abelardo
350e98ac4de8f224b6224252a326814f
600
http://orcid.org/0000-0002-3645-435X
Fliegert, Ralf
e4c92ba9ca10e119d57d1ddd28855a02
500
Guse, Andreas H
01c578ce26981ff31d38b7bd0c991f6c
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Department of Systems Immunology, Helmholtz Centre for Infection Research , Braunschweig , Germany.
2013-10-28T15:11:25Z
2013-10-28T15:11:25Z
2013
A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties. 2013, 4:277 Front Immunol
1664-3224
24065966
10.3389/fimmu.2013.00277
http://hdl.handle.net/10033/304662
Frontiers in immunology
Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic, or initiates apoptosis depends on extracellular triggers and intracellular signaling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modeling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC) is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.
en
Archived with thanks to Frontiers in immunology
A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties.
Article
2018-06-12T16:42:51Z
Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic, or initiates apoptosis depends on extracellular triggers and intracellular signaling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modeling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC) is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.
ORIGINAL
Schmeitz et al_final.pdf
Schmeitz et al_final.pdf
Open Access publication
application/pdf
2237978
https://hzi.openrepository.com/bitstream/10033/304662/1/Schmeitz%20et%20al_final.pdf
796f9de8ffd617c5ca9f7a61bbf10f71
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/304662/2/license_url
c0b3e2a72fe5e4b72fa5798bb22cd3a3
MD5
2
false
license_text
license_text
application/octet-stream
21991
https://hzi.openrepository.com/bitstream/10033/304662/3/license_text
b4eca20ce36d53f0d7292a7ee1205054
MD5
3
false
license_rdf
license_rdf
application/octet-stream
24332
https://hzi.openrepository.com/bitstream/10033/304662/4/license_rdf
306824103cdab5a2460a7737d9c97e69
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/304662/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Schmeitz et al_final.pdf.txt
Schmeitz et al_final.pdf.txt
Extracted Text
text/plain
81831
https://hzi.openrepository.com/bitstream/10033/304662/8/Schmeitz%20et%20al_final.pdf.txt
ccddf4edb86a56209011ee593a518745
MD5
8
false
THUMBNAIL
Schmeitz et al_final.pdf.jpg
Schmeitz et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
30095
https://hzi.openrepository.com/bitstream/10033/304662/9/Schmeitz%20et%20al_final.pdf.jpg
2bf0cdc3f2cbfbfe7dc0aa0305ec2c99
MD5
9
false
10033/304662
oai:hzi.openrepository.com:10033/304662
2019-08-30 11:29:47.323
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/3063992019-08-30T11:25:11Zcom_10033_620659col_10033_620660
Kempf, Harald
d0df9fa985907043b0f780c9f1c89d59
500
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Bleicher, Marcus
93411718ba96ac2e26a30be25b6fc923
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Department of Systems Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany ; Frankfurt Institute for Advanced Studies, Frankfurt, Germany.
2013-12-06T11:24:45Z
2013-12-06T11:24:45Z
2013-11
In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids. 2013, 9 (11):e1003295 PLoS Comput. Biol.
1553-7358
24244120
10.1371/journal.pcbi.1003295
http://hdl.handle.net/10033/306399
PLoS computational biology
Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle and consequently induce a collective development of radiosensitivity in tumours. Although this effect has been regularly described in experiments it is currently not exploited in clinical practice and thus a large potential for optimisation is missed. We present an agent-based model for three-dimensional tumour spheroid growth which has been combined with an irradiation damage and kinetics model. We predict the dynamic response of the overall tumour radiosensitivity to delivered radiation doses and describe corresponding time windows of increased or decreased radiation sensitivity. The degree of cell cycle resynchronisation in response to radiation delivery was identified as a main determinant of the transient periods of low and high radiosensitivity enhancement. A range of selected clinical fractionation schemes is examined and new triggered schedules are tested which aim to maximise the effect of the radiation-induced sensitivity enhancement. We find that the cell cycle resynchronisation can yield a strong increase in therapy effectiveness, if employed correctly. While the individual timing of sensitive periods will depend on the exact cell and radiation types, enhancement is a universal effect which is present in every tumour and accordingly should be the target of experimental investigation. Experimental observables which can be assessed non-invasively and with high spatio-temporal resolution have to be connected to the radiosensitivity enhancement in order to allow for a possible tumour-specific design of highly efficient treatment schedules based on induced cell cycle synchronisation.
en
Archived with thanks to PLoS computational biology
In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids.
Article
2018-06-13T09:08:59Z
Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle and consequently induce a collective development of radiosensitivity in tumours. Although this effect has been regularly described in experiments it is currently not exploited in clinical practice and thus a large potential for optimisation is missed. We present an agent-based model for three-dimensional tumour spheroid growth which has been combined with an irradiation damage and kinetics model. We predict the dynamic response of the overall tumour radiosensitivity to delivered radiation doses and describe corresponding time windows of increased or decreased radiation sensitivity. The degree of cell cycle resynchronisation in response to radiation delivery was identified as a main determinant of the transient periods of low and high radiosensitivity enhancement. A range of selected clinical fractionation schemes is examined and new triggered schedules are tested which aim to maximise the effect of the radiation-induced sensitivity enhancement. We find that the cell cycle resynchronisation can yield a strong increase in therapy effectiveness, if employed correctly. While the individual timing of sensitive periods will depend on the exact cell and radiation types, enhancement is a universal effect which is present in every tumour and accordingly should be the target of experimental investigation. Experimental observables which can be assessed non-invasively and with high spatio-temporal resolution have to be connected to the radiosensitivity enhancement in order to allow for a possible tumour-specific design of highly efficient treatment schedules based on induced cell cycle synchronisation.
ORIGINAL
Kempf et al_final.pdf
Kempf et al_final.pdf
Open Access publication
application/pdf
4067415
https://hzi.openrepository.com/bitstream/10033/306399/1/Kempf%20et%20al_final.pdf
f37127273ebee5da744eae699da5f851
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/306399/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
20637
https://hzi.openrepository.com/bitstream/10033/306399/3/license_text
3502e4e55cdd12598f770edf56010391
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/306399/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/306399/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Kempf et al_final.pdf.txt
Kempf et al_final.pdf.txt
Extracted Text
text/plain
80295
https://hzi.openrepository.com/bitstream/10033/306399/8/Kempf%20et%20al_final.pdf.txt
4528eb032982ca0f7fc2cdf8ae000cc5
MD5
8
false
THUMBNAIL
Kempf et al_final.pdf.jpg
Kempf et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
26911
https://hzi.openrepository.com/bitstream/10033/306399/9/Kempf%20et%20al_final.pdf.jpg
3a0bd29fc4ec98af5929e179ef5f95b8
MD5
9
false
10033/306399
oai:hzi.openrepository.com:10033/306399
2019-08-30 11:25:11.095
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3116162019-08-30T11:25:11Zcom_10033_620659col_10033_620660
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Bahrami, Fariba
a0e05e708c4f84aeaa4fce795719087d
500
Janahmadi, Mahyar
0e082532406902986bfb18ac5978de81
500
Milanez-Almeida, Pedro
febea14ec6f9a72e61fde7dd4887333e
500
Huehn, Jochen
81855dd40035a02edad8ee83ce210282
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
2014-01-21T12:58:19Z
2014-01-21T12:58:19Z
2013
A mathematical model of immune activation with a unified self-nonself concept. 2013, 4:474 Front Immunol
1664-3224
24409179
10.3389/fimmu.2013.00474
http://hdl.handle.net/10033/311616
Frontiers in immunology
The adaptive immune system reacts against pathogenic nonself, whereas it normally remains tolerant to self. The initiation of an immune response requires a critical antigen(Ag)-stimulation and a critical number of Ag-specific T cells. Autoreactive T cells are not completely deleted by thymic selection and partially present in the periphery of healthy individuals that respond in certain physiological conditions. A number of experimental and theoretical models are based on the concept that structural differences discriminate self from nonself. In this article, we establish a mathematical model for immune activation in which self and nonself are not distinguished. The model considers the dynamic interplay of conventional T cells, regulatory T cells (Tregs), and IL-2 molecules and shows that the renewal rate ratio of resting Tregs to naïve T cells as well as the proliferation rate of activated T cells determine the probability of immune stimulation. The actual initiation of an immune response, however, relies on the absolute renewal rate of naïve T cells. This result suggests that thymic selection reduces the probability of autoimmunity by increasing the Ag-stimulation threshold of self reaction which is established by selection of a low number of low-avidity autoreactive T cells balanced with a proper number of Tregs. The stability analysis of the ordinary differential equation model reveals three different possible immune reactions depending on critical levels of Ag-stimulation: a subcritical stimulation, a threshold stimulation inducing a proper immune response, and an overcritical stimulation leading to chronic co-existence of Ag and immune activity. The model exhibits oscillatory solutions in the case of persistent but moderate Ag-stimulation, while the system returns to the homeostatic state upon Ag clearance. In this unifying concept, self and nonself appear as a result of shifted Ag-stimulation thresholds which delineate these three regimes of immune activation.
en
Archived with thanks to Frontiers in immunology
A mathematical model of immune activation with a unified self-nonself concept.
Article
2018-06-13T01:33:43Z
The adaptive immune system reacts against pathogenic nonself, whereas it normally remains tolerant to self. The initiation of an immune response requires a critical antigen(Ag)-stimulation and a critical number of Ag-specific T cells. Autoreactive T cells are not completely deleted by thymic selection and partially present in the periphery of healthy individuals that respond in certain physiological conditions. A number of experimental and theoretical models are based on the concept that structural differences discriminate self from nonself. In this article, we establish a mathematical model for immune activation in which self and nonself are not distinguished. The model considers the dynamic interplay of conventional T cells, regulatory T cells (Tregs), and IL-2 molecules and shows that the renewal rate ratio of resting Tregs to naïve T cells as well as the proliferation rate of activated T cells determine the probability of immune stimulation. The actual initiation of an immune response, however, relies on the absolute renewal rate of naïve T cells. This result suggests that thymic selection reduces the probability of autoimmunity by increasing the Ag-stimulation threshold of self reaction which is established by selection of a low number of low-avidity autoreactive T cells balanced with a proper number of Tregs. The stability analysis of the ordinary differential equation model reveals three different possible immune reactions depending on critical levels of Ag-stimulation: a subcritical stimulation, a threshold stimulation inducing a proper immune response, and an overcritical stimulation leading to chronic co-existence of Ag and immune activity. The model exhibits oscillatory solutions in the case of persistent but moderate Ag-stimulation, while the system returns to the homeostatic state upon Ag clearance. In this unifying concept, self and nonself appear as a result of shifted Ag-stimulation thresholds which delineate these three regimes of immune activation.
ORIGINAL
Khailaie et al_final.pdf
Khailaie et al_final.pdf
Open Access publication
application/pdf
7119896
https://hzi.openrepository.com/bitstream/10033/311616/1/Khailaie%20et%20al_final.pdf
2c81635ef8ad16aeadb215c0931a8742
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/311616/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21011
https://hzi.openrepository.com/bitstream/10033/311616/3/license_text
d1f59b8c1de3c261e71f917b82f73499
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/311616/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/311616/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Khailaie et al_final.pdf.txt
Khailaie et al_final.pdf.txt
Extracted Text
text/plain
80194
https://hzi.openrepository.com/bitstream/10033/311616/8/Khailaie%20et%20al_final.pdf.txt
30d0226ba2839ade90a964a1ed3a3e72
MD5
8
false
THUMBNAIL
Khailaie et al_final.pdf.jpg
Khailaie et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
29690
https://hzi.openrepository.com/bitstream/10033/311616/9/Khailaie%20et%20al_final.pdf.jpg
2a0dc106502dfae2adb8c5ba3d52e67a
MD5
9
false
10033/311616
oai:hzi.openrepository.com:10033/311616
2019-08-30 11:25:11.455
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3117182019-08-30T11:27:46Zcom_10033_620659col_10033_620660
Jain, Harsh Vardhan
f66a700ac93a608e9060540d8fc7d804
500
Richardson, Alan
c7ae43310ce652a4f927ef9991f6f10d
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Byrne, Helen M
c953199ddcbd7826aad36e1d274e4f82
500
2014-01-23T08:59:14Z
2014-01-23T08:59:14Z
2014
Exploiting the Synergy between Carboplatin and ABT-737 in the Treatment of Ovarian Carcinomas. 2014, 9 (1):e81582 PLoS ONE
1932-6203
24400068
10.1371/journal.pone.0081582
http://hdl.handle.net/10033/311718
PloS one
Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics.
en
Archived with thanks to PloS one
Exploiting the Synergy between Carboplatin and ABT-737 in the Treatment of Ovarian Carcinomas.
Article
2018-06-13T00:18:45Z
Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics.
ORIGINAL
jain et al_final.pdf
jain et al_final.pdf
Open Access publication
application/pdf
779351
https://hzi.openrepository.com/bitstream/10033/311718/1/jain%20et%20al_final.pdf
c1985459f5db077fe3a8de21e48c1f42
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/311718/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21011
https://hzi.openrepository.com/bitstream/10033/311718/3/license_text
d1f59b8c1de3c261e71f917b82f73499
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/311718/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/311718/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
jain et al_final.pdf.txt
jain et al_final.pdf.txt
Extracted Text
text/plain
56760
https://hzi.openrepository.com/bitstream/10033/311718/8/jain%20et%20al_final.pdf.txt
bf51658b12616d07767edf5671d9c0b0
MD5
8
false
THUMBNAIL
jain et al_final.pdf.jpg
jain et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
33032
https://hzi.openrepository.com/bitstream/10033/311718/9/jain%20et%20al_final.pdf.jpg
98b99536c5f16eb5dd1eeb11422cc9c4
MD5
9
false
10033/311718
oai:hzi.openrepository.com:10033/311718
2019-08-30 11:27:46.445
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3226962019-08-30T11:34:21Zcom_10033_620659col_10033_620660
Hernandez-Vargas, Esteban Abelardo
350e98ac4de8f224b6224252a326814f
600
http://orcid.org/0000-0002-3645-435X
Colaneri, Patrizio
b9aed58ef94a5a896ba1327d02085a0f
500
Middleton, Richard H.
fc6240d45da0213e0b83a0a1f292798c
500
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2014-07-09T12:19:54Z
2014-07-09T12:19:54Z
2014-07-09
Optimal therapy scheduling for a simplified HIV infection model 2013, 49 (9):2874 Automatica
51098
10.1016/j.automatica.2013.06.001
http://hdl.handle.net/10033/322696
Automatica
http://linkinghub.elsevier.com/retrieve/pii/S0005109813003154
Archived with thanks to Automatica
Optimal therapy scheduling for a simplified HIV infection model
Article
2018-06-12T22:42:18Z
ORIGINAL
Hernandez-Vargas et al_final.pdf
Hernandez-Vargas et al_final.pdf
allowed publisher's PDF
application/pdf
888170
https://hzi.openrepository.com/bitstream/10033/322696/1/Hernandez-Vargas%20et%20al_final.pdf
a25c9c1abee78549f9ab69ff0298b285
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/322696/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
22424
https://hzi.openrepository.com/bitstream/10033/322696/3/license_text
9d4aa3148f8600b6240582f6981c8f65
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/322696/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/322696/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Hernandez-Vargas et al_final.pdf.txt
Hernandez-Vargas et al_final.pdf.txt
Extracted Text
text/plain
42612
https://hzi.openrepository.com/bitstream/10033/322696/8/Hernandez-Vargas%20et%20al_final.pdf.txt
cb0efeef09787f6a1a44aa46c429fd2c
MD5
8
false
THUMBNAIL
Hernandez-Vargas et al_final.pdf.jpg
Hernandez-Vargas et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
26979
https://hzi.openrepository.com/bitstream/10033/322696/9/Hernandez-Vargas%20et%20al_final.pdf.jpg
d30322a0123db7dc5cf5f004afbcb8c5
MD5
9
false
elsevier-thumbnail.png
application/octet-stream
145646
https://hzi.openrepository.com/bitstream/10033/322696/10/elsevier-thumbnail.png
2cc220e10109313b9ed56078f368710d
MD5
10
false
10033/322696
oai:hzi.openrepository.com:10033/322696
2019-08-30 11:34:21.086
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3228192019-08-30T11:37:44Zcom_10033_620659col_10033_620660
Haering, Matthias
529f1e0595936b22f8b6bd8eb0a37672
500
Hördt, Andreas
974496f0d9cd176d84eab34d29b538ff
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Hernandez-Vargas, Esteban Abelardo
350e98ac4de8f224b6224252a326814f
600
http://orcid.org/0000-0002-3645-435X
2014-07-11T13:32:02Z
2014-07-11T13:32:02Z
2014
Computational Study to Determine When to Initiate and Alternate Therapy in HIV Infection. 2014, 2014:472869 Biomed Res Int
2314-6141
24900966
10.1155/2014/472869
http://hdl.handle.net/10033/322819
BioMed research international
HIV is a widespread viral infection without cure. Drug treatment has transformed HIV disease into a treatable long-term infection. However, the appearance of mutations within the viral genome reduces the susceptibility of HIV to drugs. Therefore, a key goal is to extend the time until patients exhibit resistance to all existing drugs. Current HIV treatment guidelines seem poorly supported as practitioners have not achieved a consensus on the optimal time to initiate and to switch antiretroviral treatments. We contribute to this discussion with predictions derived from a mathematical model of HIV dynamics. Our results indicate that early therapy initiation (within 2 years postinfection) is critical to delay AIDS progression. For patients who have not received any therapy during the first 3 years postinfection, switch in response to virological failure may outperform proactive switching strategies. In case that proactive switching is opted, the switching time between therapies should not be larger than 100 days. Further clinical trials are needed to either confirm or falsify these predictions.
en
Archived with thanks to BioMed research international
Computational Study to Determine When to Initiate and Alternate Therapy in HIV Infection.
Article
2018-06-13T04:24:44Z
HIV is a widespread viral infection without cure. Drug treatment has transformed HIV disease into a treatable long-term infection. However, the appearance of mutations within the viral genome reduces the susceptibility of HIV to drugs. Therefore, a key goal is to extend the time until patients exhibit resistance to all existing drugs. Current HIV treatment guidelines seem poorly supported as practitioners have not achieved a consensus on the optimal time to initiate and to switch antiretroviral treatments. We contribute to this discussion with predictions derived from a mathematical model of HIV dynamics. Our results indicate that early therapy initiation (within 2 years postinfection) is critical to delay AIDS progression. For patients who have not received any therapy during the first 3 years postinfection, switch in response to virological failure may outperform proactive switching strategies. In case that proactive switching is opted, the switching time between therapies should not be larger than 100 days. Further clinical trials are needed to either confirm or falsify these predictions.
ORIGINAL
Haering et al_final.pdf
Haering et al_final.pdf
Open Access publication
application/pdf
2010182
https://hzi.openrepository.com/bitstream/10033/322819/1/Haering%20et%20al_final.pdf
b1573556529751e2c5bf21d58dd0af85
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/322819/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
22424
https://hzi.openrepository.com/bitstream/10033/322819/3/license_text
9d4aa3148f8600b6240582f6981c8f65
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/322819/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/322819/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Haering et al_final.pdf.txt
Haering et al_final.pdf.txt
Extracted Text
text/plain
39946
https://hzi.openrepository.com/bitstream/10033/322819/8/Haering%20et%20al_final.pdf.txt
78cf07697cf82734c6d43709d45d1648
MD5
8
false
THUMBNAIL
Haering et al_final.pdf.jpg
Haering et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
32680
https://hzi.openrepository.com/bitstream/10033/322819/9/Haering%20et%20al_final.pdf.jpg
e067c57a706604f787a64d01c0edeb5a
MD5
9
false
10033/322819
oai:hzi.openrepository.com:10033/322819
2019-08-30 11:37:44.638
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3385772019-08-30T11:34:19Zcom_10033_620659col_10033_620660
Alanis, Alma Y.
1ca556daf0c68cfd169b7c75bc24d4ed
500
Hernandez-Gonzalez, Miguel
316a588edf2855260b40306c94894391
500
Hernandez-Vargas, Esteban Abelardo
350e98ac4de8f224b6224252a326814f
600
http://orcid.org/0000-0002-3645-435X
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2015-01-20T14:41:09Z
2015-01-20T14:41:09Z
2014-11
Observers for biological systems 2014, 24:1175 Applied Soft Computing
15684946
10.1016/j.asoc.2013.10.028
http://hdl.handle.net/10033/338577
Applied Soft Computing
http://linkinghub.elsevier.com/retrieve/pii/S1568494613003621
Observers for biological systems
Article
2018-06-13T09:19:52Z
ORIGINAL
Alanis et al_final.pdf
Alanis et al_final.pdf
submitted manuscript
application/pdf
1075292
https://hzi.openrepository.com/bitstream/10033/338577/1/Alanis%20et%20al_final.pdf
4c56eade20a1088e7321dda4fe46833a
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/338577/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
23389
https://hzi.openrepository.com/bitstream/10033/338577/3/license_text
52b907285a37a480de2a5acd7165659c
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/338577/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/338577/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Alanis et al_final.pdf.txt
Alanis et al_final.pdf.txt
Extracted Text
text/plain
38811
https://hzi.openrepository.com/bitstream/10033/338577/8/Alanis%20et%20al_final.pdf.txt
90e597d80e2f362c63d581f3d685e5c3
MD5
8
false
THUMBNAIL
Alanis et al_final.pdf.jpg
Alanis et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
25845
https://hzi.openrepository.com/bitstream/10033/338577/9/Alanis%20et%20al_final.pdf.jpg
78dcbca064e90024abf01ce2032e8592
MD5
9
false
elsevier-thumbnail.png
application/octet-stream
134684
https://hzi.openrepository.com/bitstream/10033/338577/10/elsevier-thumbnail.png
74557571ae7a9269c85ba6ad5564329d
MD5
10
false
10033/338577
oai:hzi.openrepository.com:10033/338577
2019-08-30 11:34:19.026
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/3468802019-08-30T11:24:31Zcom_10033_620659col_10033_620660
Breitsprecher, Dennis
3698d4bf8b44020062bf468e97b5d965
500
Kiesewetter, Antje K
d0b2683b1d1356d1f3678f6407574c46
500
Linkner, Joern
33d47b5dff855e8473faa00bfafe102a
500
Vinzenz, Marlene
69a0f68ede7dc6f685d4dc1e31df271a
500
Stradal, Theresia E B
52ab204965e535010ac568c83571af44
500
Small, John Victor
b3d105f0024761aa7cc545b1998ac650
500
Curth, Ute
5b51896d39625540134602537cc958a4
500
Dickinson, Richard B
ebaa1492919ec77a6b39c79c4065b1cd
500
Faix, Jan
3a94710daa2c4770050204bff0b1c340
500
2015-03-19T09:34:39Z
2015-03-19T09:34:39Z
2011-02-02
Molecular mechanism of Ena/VASP-mediated actin-filament elongation. 2011, 30 (3):456-67 EMBO J.
1460-2075
21217643
10.1038/emboj.2010.348
http://hdl.handle.net/10033/346880
The EMBO journal
Ena/VASP proteins are implicated in a variety of fundamental cellular processes including axon guidance and cell migration. In vitro, they enhance elongation of actin filaments, but at rates differing in nearly an order of magnitude according to species, raising questions about the molecular determinants of rate control. Chimeras from fast and slow elongating VASP proteins were generated and their ability to promote actin polymerization and to bind G-actin was assessed. By in vitro TIRF microscopy as well as thermodynamic and kinetic analyses, we show that the velocity of VASP-mediated filament elongation depends on G-actin recruitment by the WASP homology 2 motif. Comparison of the experimentally observed elongation rates with a quantitative mathematical model moreover revealed that Ena/VASP-mediated filament elongation displays a saturation dependence on the actin monomer concentration, implying that Ena/VASP proteins, independent of species, are fully saturated with actin in vivo and generally act as potent filament elongators. Moreover, our data showed that spontaneous addition of monomers does not occur during processive VASP-mediated filament elongation on surfaces, suggesting that most filament formation in cells is actively controlled.
en
Actins
Amino Acid Sequence
Cell Movement
DNA-Binding Proteins
Kinetics
Microscopy, Fluorescence
Models, Biological
Molecular Sequence Data
Peptides
Polymerization
Recombinant Fusion Proteins
Time-Lapse Imaging
Molecular mechanism of Ena/VASP-mediated actin-filament elongation.
Article
2018-06-13T01:19:29Z
Ena/VASP proteins are implicated in a variety of fundamental cellular processes including axon guidance and cell migration. In vitro, they enhance elongation of actin filaments, but at rates differing in nearly an order of magnitude according to species, raising questions about the molecular determinants of rate control. Chimeras from fast and slow elongating VASP proteins were generated and their ability to promote actin polymerization and to bind G-actin was assessed. By in vitro TIRF microscopy as well as thermodynamic and kinetic analyses, we show that the velocity of VASP-mediated filament elongation depends on G-actin recruitment by the WASP homology 2 motif. Comparison of the experimentally observed elongation rates with a quantitative mathematical model moreover revealed that Ena/VASP-mediated filament elongation displays a saturation dependence on the actin monomer concentration, implying that Ena/VASP proteins, independent of species, are fully saturated with actin in vivo and generally act as potent filament elongators. Moreover, our data showed that spontaneous addition of monomers does not occur during processive VASP-mediated filament elongation on surfaces, suggesting that most filament formation in cells is actively controlled.
ORIGINAL
breitsprecher et al_final.pdf
breitsprecher et al_final.pdf
Open Access publication
application/pdf
1133112
https://hzi.openrepository.com/bitstream/10033/346880/1/breitsprecher%20et%20al_final.pdf
4568dea9c7b3938dd61e3faa3d1cd7e0
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/346880/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
22864
https://hzi.openrepository.com/bitstream/10033/346880/3/license_text
8e37d7b9d509ac90b985587e2924ad4f
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/346880/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/346880/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
breitsprecher et al_final.pdf.txt
breitsprecher et al_final.pdf.txt
Extracted Text
text/plain
68214
https://hzi.openrepository.com/bitstream/10033/346880/8/breitsprecher%20et%20al_final.pdf.txt
a8f944cb6e904b5c946b9eb389857762
MD5
8
false
THUMBNAIL
breitsprecher et al_final.pdf.jpg
breitsprecher et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
26369
https://hzi.openrepository.com/bitstream/10033/346880/9/breitsprecher%20et%20al_final.pdf.jpg
fa82725541694e54923cc29f7a2c0182
MD5
9
false
10033/346880
oai:hzi.openrepository.com:10033/346880
2019-08-30 11:24:31.72
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/3624832019-08-30T11:26:13Zcom_10033_620659col_10033_620660
Jain, Harsh Vardhan
f66a700ac93a608e9060540d8fc7d804
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
2015-04-09T09:37:38Z
2015-04-09T09:37:38Z
2011-02-01
The molecular basis of synergism between carboplatin and ABT-737 therapy targeting ovarian carcinomas. 2011, 71 (3):705-15 Cancer Res.
1538-7445
21169413
10.1158/0008-5472.CAN-10-3174
http://hdl.handle.net/10033/362483
Cancer research
Resistance to standard chemotherapy (carboplatin + paclitaxel) is one of the leading causes of therapeutic failure in ovarian carcinomas. Emergence of chemoresistance has been shown to be mediated in part by members of the Bcl family of proteins including the antiapoptotic protein Bcl-x(L), whose expression is correlated with shorter disease-free intervals in recurrent disease. ABT-737 is an example of one of the first small-molecule inhibitors of Bcl-2/Bcl-x(L) that has been shown to increase the sensitivity of ovarian cancer cells to carboplatin. To exploit the therapeutic potential of these two drugs and predict optimal doses and dose scheduling, it is essential to understand the molecular basis of their synergistic action. Here, we build and calibrate a mathematical model of ABT-737 and carboplatin action on an ovarian cancer cell line (IGROV-1). The model suggests that carboplatin treatment primes cells for ABT-737 therapy because of an increased dependence of cells with DNA damage on Bcl-x(L) for survival. Numerical simulations predict the existence of a threshold of Bcl-x(L) below which these cells are unable to recover. Furthermore, co- plus posttreatment of ABT-737 with carboplatin is predicted to be the best strategy to maximize synergism between these two drugs. A critical challenge in chemotherapy is to strike a balance between maximizing cell-kill while minimizing patient drug load. We show that the model can be used to compute minimal doses required for any desired fraction of cell kill. These results underscore the potential of the modeling work presented here as a valuable quantitative tool to aid in the translation of novel drugs such as ABT-737 from the experimental to clinical setting and highlight the need for close collaboration between modelers and experimental scientists.
en
Animals
Antineoplastic Combined Chemotherapy Protocols
Apoptosis
Biphenyl Compounds
Carboplatin
DNA Damage
Drug Administration Schedule
Drug Synergism
Female
Humans
Mice
Models, Biological
Molecular Targeted Therapy
Nitrophenols
Ovarian Neoplasms
Piperazines
Sulfonamides
bcl-X Protein
The molecular basis of synergism between carboplatin and ABT-737 therapy targeting ovarian carcinomas.
Article
2018-06-13T19:46:36Z
Resistance to standard chemotherapy (carboplatin + paclitaxel) is one of the leading causes of therapeutic failure in ovarian carcinomas. Emergence of chemoresistance has been shown to be mediated in part by members of the Bcl family of proteins including the antiapoptotic protein Bcl-x(L), whose expression is correlated with shorter disease-free intervals in recurrent disease. ABT-737 is an example of one of the first small-molecule inhibitors of Bcl-2/Bcl-x(L) that has been shown to increase the sensitivity of ovarian cancer cells to carboplatin. To exploit the therapeutic potential of these two drugs and predict optimal doses and dose scheduling, it is essential to understand the molecular basis of their synergistic action. Here, we build and calibrate a mathematical model of ABT-737 and carboplatin action on an ovarian cancer cell line (IGROV-1). The model suggests that carboplatin treatment primes cells for ABT-737 therapy because of an increased dependence of cells with DNA damage on Bcl-x(L) for survival. Numerical simulations predict the existence of a threshold of Bcl-x(L) below which these cells are unable to recover. Furthermore, co- plus posttreatment of ABT-737 with carboplatin is predicted to be the best strategy to maximize synergism between these two drugs. A critical challenge in chemotherapy is to strike a balance between maximizing cell-kill while minimizing patient drug load. We show that the model can be used to compute minimal doses required for any desired fraction of cell kill. These results underscore the potential of the modeling work presented here as a valuable quantitative tool to aid in the translation of novel drugs such as ABT-737 from the experimental to clinical setting and highlight the need for close collaboration between modelers and experimental scientists.
ORIGINAL
jain-meyer et al_final.pdf
jain-meyer et al_final.pdf
Open Access publication
application/pdf
880825
https://hzi.openrepository.com/bitstream/10033/362483/1/jain-meyer%20et%20al_final.pdf
9c8b49793ca27be87b14c236f429e04e
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/362483/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
23250
https://hzi.openrepository.com/bitstream/10033/362483/3/license_text
7d581b5718397a31db385dc7797ba7ba
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/362483/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/362483/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
jain-meyer et al_final.pdf.txt
jain-meyer et al_final.pdf.txt
Extracted Text
text/plain
56947
https://hzi.openrepository.com/bitstream/10033/362483/8/jain-meyer%20et%20al_final.pdf.txt
544e022ecf66ebab277a9aad341fc566
MD5
8
false
THUMBNAIL
jain-meyer et al_final.pdf.jpg
jain-meyer et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
23912
https://hzi.openrepository.com/bitstream/10033/362483/9/jain-meyer%20et%20al_final.pdf.jpg
6cd36470c501e9ce40828412a9ae9095
MD5
9
false
10033/362483
oai:hzi.openrepository.com:10033/362483
2019-08-30 11:26:13.25
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/5662652019-08-30T11:25:11Zcom_10033_620659col_10033_620660
Dehghany, Jaber
763519d6de38b945a2f96901ec0a5047
500
Hoboth, Peter
c288756440dabb25211445d36e137e1c
500
Ivanova, Anna
d89a9b28e4bf7e5617862c888fd8adff
500
Mziaut, Hassan
4074e87d99e4eb39e8cb1737676f902d
500
Müller, Andreas
390aec6617424eec39c6976a1887e77f
500
Kalaidzidis, Yannis
c2c25230dd2497ce164eacd1344a2f03
500
Solimena, Michele
b1ac3e3638aa1afc53550bc7e555c91e
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2015-08-13T09:04:22Z
2015-08-13T09:04:22Z
2015-08
A Spatial Model of Insulin-Granule Dynamics in Pancreatic β-Cells. 2015, 16 (8):797-813 Traffic
1600-0854
25809669
10.1111/tra.12286
http://hdl.handle.net/10033/566265
Traffic (Copenhagen, Denmark)
Insulin secretion from pancreatic β-cells in response to sudden glucose stimulation is biphasic. Prolonged secretion in vivo requires synthesis, delivery to the plasma membrane (PM) and exocytosis of insulin secretory granules (SGs). Here, we provide the first agent-based space-resolved model for SG dynamics in pancreatic β-cells. Using recent experimental data, we consider a single β-cell with identical SGs moving on a phenomenologically represented cytoskeleton network. A single exocytotic machinery mediates SG exocytosis on the PM. This novel model reproduces the measured spatial organization of SGs and insulin secretion patterns under different stimulation protocols. It proposes that the insulin potentiation effect and the rising second-phase secretion are mainly due to the increasing number of docking sites on the PM. Furthermore, it shows that 6 min after glucose stimulation, the 'newcomer' SGs are recruited from a region within less than 600 nm from the PM.
en
A Spatial Model of Insulin-Granule Dynamics in Pancreatic β-Cells.
Article
2016-08-01T00:00:00Z
Insulin secretion from pancreatic β-cells in response to sudden glucose stimulation is biphasic. Prolonged secretion in vivo requires synthesis, delivery to the plasma membrane (PM) and exocytosis of insulin secretory granules (SGs). Here, we provide the first agent-based space-resolved model for SG dynamics in pancreatic β-cells. Using recent experimental data, we consider a single β-cell with identical SGs moving on a phenomenologically represented cytoskeleton network. A single exocytotic machinery mediates SG exocytosis on the PM. This novel model reproduces the measured spatial organization of SGs and insulin secretion patterns under different stimulation protocols. It proposes that the insulin potentiation effect and the rising second-phase secretion are mainly due to the increasing number of docking sites on the PM. Furthermore, it shows that 6 min after glucose stimulation, the 'newcomer' SGs are recruited from a region within less than 600 nm from the PM.
ORIGINAL
Dehghani et al_final.pdf
Dehghani et al_final.pdf
submitted manuscript
application/pdf
3282804
https://hzi.openrepository.com/bitstream/10033/566265/1/Dehghani%20et%20al_final.pdf
9794435ad63fbe28220e161385348e33
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/566265/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21759
https://hzi.openrepository.com/bitstream/10033/566265/3/license_text
1ebd32f1649e657e6dd4a7f3011f8454
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/566265/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/566265/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Dehghani et al_final.pdf.txt
Dehghani et al_final.pdf.txt
Extracted Text
text/plain
70949
https://hzi.openrepository.com/bitstream/10033/566265/8/Dehghani%20et%20al_final.pdf.txt
9cda1b951a757eede74a4975d2199c2c
MD5
8
false
THUMBNAIL
Dehghani et al_final.pdf.jpg
Dehghani et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
28542
https://hzi.openrepository.com/bitstream/10033/566265/9/Dehghani%20et%20al_final.pdf.jpg
785f8d280c6909cea612affa9e096fd6
MD5
9
false
10033/566265
oai:hzi.openrepository.com:10033/566265
2019-08-30 11:25:11.3
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/5773122019-08-30T11:25:11Zcom_10033_620659col_10033_620660
Boianelli, Alessandro
8d9960dd5670271aff55581d1daa4dc2
500
Pettini, Elena
80610902f2213c03e77981d5d53bd3a3
500
Prota, Gennaro
f1babbca43410fda79e13c209383add1
500
Medaglini, Donata
48e43a5b6dec9c00e2103f940a4baa9a
500
Vicino, Antonio
4a90dd5004a1fb00be65a19fbe6a5d2b
500
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2015-09-15T08:47:04Z
2015-09-15T08:47:04Z
2015
A Stochastic Model for CD4+ T Cell Proliferation and Dissemination Network in Primary Immune Response. 2015, 10 (8):e0135787 PLoS ONE
1932-6203
26301680
10.1371/journal.pone.0135787
http://hdl.handle.net/10033/577312
PloS one
The study of the initial phase of the adaptive immune response after first antigen encounter provides essential information on the magnitude and quality of the immune response. This phase is characterized by proliferation and dissemination of T cells in the lymphoid organs. Modeling and identifying the key features of this phenomenon may provide a useful tool for the analysis and prediction of the effects of immunization. This knowledge can be effectively exploited in vaccinology, where it is of interest to evaluate and compare the responses to different vaccine formulations. The objective of this paper is to construct a stochastic model based on branching process theory, for the dissemination network of antigen-specific CD4+ T cells. The devised model is validated on in vivo animal experimental data. The model presented has been applied to the vaccine immunization context making references to simple proliferation laws that take into account division, death and quiescence, but it can also be applied to any context where it is of interest to study the dynamic evolution of a population.
en
A Stochastic Model for CD4+ T Cell Proliferation and Dissemination Network in Primary Immune Response.
Article
2018-06-13T07:28:36Z
The study of the initial phase of the adaptive immune response after first antigen encounter provides essential information on the magnitude and quality of the immune response. This phase is characterized by proliferation and dissemination of T cells in the lymphoid organs. Modeling and identifying the key features of this phenomenon may provide a useful tool for the analysis and prediction of the effects of immunization. This knowledge can be effectively exploited in vaccinology, where it is of interest to evaluate and compare the responses to different vaccine formulations. The objective of this paper is to construct a stochastic model based on branching process theory, for the dissemination network of antigen-specific CD4+ T cells. The devised model is validated on in vivo animal experimental data. The model presented has been applied to the vaccine immunization context making references to simple proliferation laws that take into account division, death and quiescence, but it can also be applied to any context where it is of interest to study the dynamic evolution of a population.
ORIGINAL
Bioanelli et al_final.pdf
Bioanelli et al_final.pdf
Open Access publication
application/pdf
861528
https://hzi.openrepository.com/bitstream/10033/577312/1/Bioanelli%20et%20al_final.pdf
f51a580094ff5f28595ba9c04bf44447
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/577312/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21597
https://hzi.openrepository.com/bitstream/10033/577312/3/license_text
54dd59d40230fe99c6f8f5992623f9e2
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/577312/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/577312/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Bioanelli et al_final.pdf.txt
Bioanelli et al_final.pdf.txt
Extracted Text
text/plain
50214
https://hzi.openrepository.com/bitstream/10033/577312/8/Bioanelli%20et%20al_final.pdf.txt
575b98f919d2e2222e5f686e53a5f0b9
MD5
8
false
THUMBNAIL
Bioanelli et al_final.pdf.jpg
Bioanelli et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
28627
https://hzi.openrepository.com/bitstream/10033/577312/9/Bioanelli%20et%20al_final.pdf.jpg
47d7d1675937c685ca80da366238660d
MD5
9
false
10033/577312
oai:hzi.openrepository.com:10033/577312
2019-08-30 11:25:11.414
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/5786282019-08-30T11:33:00Zcom_10033_620659col_10033_620660
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2015-09-23T13:51:18Z
2015-09-23T13:51:18Z
2015
Commentary: "Can Selective MHC Downregulation Explain the Specificity and Genetic Diversity of NK Cell Receptors?". 2015, 6:444 Front Immunol
1664-3224
26379675
10.3389/fimmu.2015.00444
http://hdl.handle.net/10033/578628
Frontiers in immunology
en
Commentary: "Can Selective MHC Downregulation Explain the Specificity and Genetic Diversity of NK Cell Receptors?".
Article
2018-06-13T00:11:49Z
ORIGINAL
Robert_final.pdf
Robert_final.pdf
Open Access publication
application/pdf
502174
https://hzi.openrepository.com/bitstream/10033/578628/1/Robert_final.pdf
96324ca4957deb4d344f0b5108f46121
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/578628/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21597
https://hzi.openrepository.com/bitstream/10033/578628/3/license_text
54dd59d40230fe99c6f8f5992623f9e2
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/578628/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/578628/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Robert_final.pdf.txt
Robert_final.pdf.txt
Extracted Text
text/plain
9643
https://hzi.openrepository.com/bitstream/10033/578628/8/Robert_final.pdf.txt
4c8f7362acf78b450a4a4373e7d42416
MD5
8
false
THUMBNAIL
Robert_final.pdf.jpg
Robert_final.pdf.jpg
Generated Thumbnail
image/jpeg
27598
https://hzi.openrepository.com/bitstream/10033/578628/9/Robert_final.pdf.jpg
ccb0f7a0afc5898c1a75a3ec7e95c388
MD5
9
false
10033/578628
oai:hzi.openrepository.com:10033/578628
2019-08-30 11:33:00.073
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/5801152019-08-30T11:25:43Zcom_10033_620659col_10033_620660
Nguyen, Van Kinh
fe3caa580f65be65f908fef73dff4421
500
Binder, Sebastian C
ca9fc32341dea761712a6ca7f0d7308b
600
http://orcid.org/0000-0003-1169-1786
Boianelli, Alessandro
8d9960dd5670271aff55581d1daa4dc2
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Hernandez-Vargas, Esteban Abelardo
350e98ac4de8f224b6224252a326814f
600
http://orcid.org/0000-0002-3645-435X
Helmholtz Center for Infection Research
2015-10-22T11:44:55Z
2015-10-22T11:44:55Z
2015
Ebola virus infection modeling and identifiability problems. 2015, 6:257 Front Microbiol
1664-302X
25914675
10.3389/fmicb.2015.00257
http://hdl.handle.net/10033/580115
Frontiers in microbiology
The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection.
en
Ebola virus infection modeling and identifiability problems.
Article
2018-06-12T21:36:22Z
The recent outbreaks of Ebola virus (EBOV) infections have underlined the impact of the virus as a major threat for human health. Due to the high biosafety classification of EBOV (level 4), basic research is very limited. Therefore, the development of new avenues of thinking to advance quantitative comprehension of the virus and its interaction with the host cells is urgently needed to tackle this lethal disease. Mathematical modeling of the EBOV dynamics can be instrumental to interpret Ebola infection kinetics on quantitative grounds. To the best of our knowledge, a mathematical modeling approach to unravel the interaction between EBOV and the host cells is still missing. In this paper, a mathematical model based on differential equations is used to represent the basic interactions between EBOV and wild-type Vero cells in vitro. Parameter sets that represent infectivity of pathogens are estimated for EBOV infection and compared with influenza virus infection kinetics. The average infecting time of wild-type Vero cells by EBOV is slower than in influenza infection. Simulation results suggest that the slow infecting time of EBOV could be compensated by its efficient replication. This study reveals several identifiability problems and what kind of experiments are necessary to advance the quantification of EBOV infection. A first mathematical approach of EBOV dynamics and the estimation of standard parameters in viral infections kinetics is the key contribution of this work, paving the way for future modeling works on EBOV infection.
ORIGINAL
nguyen et al_final.pdf
nguyen et al_final.pdf
Open Access publication
application/pdf
2832915
https://hzi.openrepository.com/bitstream/10033/580115/1/nguyen%20et%20al_final.pdf
5830f6d257f431fa74451a5c42b543fe
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/580115/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
21597
https://hzi.openrepository.com/bitstream/10033/580115/3/license_text
54dd59d40230fe99c6f8f5992623f9e2
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/580115/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/580115/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
nguyen et al_final.pdf.txt
nguyen et al_final.pdf.txt
Extracted Text
text/plain
54967
https://hzi.openrepository.com/bitstream/10033/580115/6/nguyen%20et%20al_final.pdf.txt
e37f1f201fcab6cf09dff98148fc6fb6
MD5
6
false
THUMBNAIL
nguyen et al_final.pdf.jpg
nguyen et al_final.pdf.jpg
Generated Thumbnail
image/jpeg
27010
https://hzi.openrepository.com/bitstream/10033/580115/7/nguyen%20et%20al_final.pdf.jpg
f4635103bf83c11a19b79c5f6cc3d5ef
MD5
7
false
10033/580115
oai:hzi.openrepository.com:10033/580115
2019-08-30 11:25:43.537
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/5969602019-08-30T11:25:43Zcom_10033_620659col_10033_620660
Nakagawa, Rinako
401e60c102b23e0d0a150221be56a082
500
Leyland, Rebecca
aa21cef3d27d69f17cdf7d098f7886a2
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Lu, Dong
e862711483dd1191c57f01b90b9e2a80
500
Turner, Martin
b2cb186beae8885baa9590e07179d3cd
500
Arbore, Giuseppina
5b83972156cbde8262e557bae6b6f455
500
Phan, Tri Giang
60d8fbffd6a9d14ac41c287f40d205f8
500
Brink, Robert
a51c19bd1c9a69efeeccbf43c58bf5b0
500
Vigorito, Elena
d7a7e8bb064aae339c534e81aa49cbd7
500
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2016-02-23T10:50:23Z
2016-02-23T10:50:23Z
2016-01-04
MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis. 2016, 126 (1):377-88 J. Clin. Invest.
1558-8238
26657861
10.1172/JCI82914
http://hdl.handle.net/10033/596960
The Journal of clinical investigation
The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood. Here, we utilized a miR-155 reporter mouse strain and showed that miR-155 is coexpressed with the proto-oncogene encoding c-MYC in positively selected B cells. Functionally, miR-155 protected positively selected c-MYC+ B cells from apoptosis, allowing clonal expansion of this population, providing an explanation as to why Mir155 deletion impairs affinity maturation and promotes the premature collapse of GCs. We determined that miR-155 directly inhibits the Jumonji family member JARID2, which enhances B cell apoptosis when overexpressed, and thereby promotes GC B cell survival. Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes.
en
MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis.
Article
2018-06-12T23:59:58Z
The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood. Here, we utilized a miR-155 reporter mouse strain and showed that miR-155 is coexpressed with the proto-oncogene encoding c-MYC in positively selected B cells. Functionally, miR-155 protected positively selected c-MYC+ B cells from apoptosis, allowing clonal expansion of this population, providing an explanation as to why Mir155 deletion impairs affinity maturation and promotes the premature collapse of GCs. We determined that miR-155 directly inhibits the Jumonji family member JARID2, which enhances B cell apoptosis when overexpressed, and thereby promotes GC B cell survival. Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes.
ORIGINAL
Nakagawa et al.pdf
Nakagawa et al.pdf
allowed PDF
application/pdf
2250149
https://hzi.openrepository.com/bitstream/10033/596960/1/Nakagawa%20et%20al.pdf
5da476ec0ed5f348ebd5942c8d9f2acf
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/596960/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
22333
https://hzi.openrepository.com/bitstream/10033/596960/3/license_text
33af6f23fea3b848a02227818b46d2ee
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/596960/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/596960/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Nakagawa et al.pdf.txt
Nakagawa et al.pdf.txt
Extracted Text
text/plain
59049
https://hzi.openrepository.com/bitstream/10033/596960/6/Nakagawa%20et%20al.pdf.txt
620a586d14b4e77894c33e03e4d7a7ef
MD5
6
false
THUMBNAIL
Nakagawa et al.pdf.jpg
Nakagawa et al.pdf.jpg
Generated Thumbnail
image/jpeg
167647
https://hzi.openrepository.com/bitstream/10033/596960/7/Nakagawa%20et%20al.pdf.jpg
e40457cddff10b9752963b529e9b6ee8
MD5
7
false
10033/596960
oai:hzi.openrepository.com:10033/596960
2019-08-30 11:25:43.57
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6008442019-08-30T11:26:42Zcom_10033_620659col_10033_620660
Jaafoura, S
ddec56d0aa5237868d4a349813a138a6
500
de Goër de Herve, M G
8d443a3e3141b5d544117c8f3cff3b27
500
Hernandez-Vargas, Esteban Abelardo
350e98ac4de8f224b6224252a326814f
600
http://orcid.org/0000-0002-3645-435X
Hendel-Chavez, H
acfee4a3c71cf1fce19aeb91d1969e70
500
Abdoh, M
1684d668f493af68ab9d69fa04e71160
500
Mateo, M C
89d52f38d9733cead87cf0a6bcbd4ead
500
Krzysiek, R
9ef74bb045258fb47c2e3b61c2d1a57b
500
Merad, M
2756509c996cafb28ebb56461dd1de96
500
Seng, R
f8f1d765049b0fbf5503cc94472325e4
500
Tardieu, M
d04daf0f184c0d949612a603d0d0c1d6
500
Delfraissy, J F
192d7e90d36876e707dd0d11795b758c
500
Goujard, C
1c8a80ca7ed44f6bc26dbd3a3fc84f7a
500
Taoufik, Y
679d6335a868f45c05e1c4e7e74915e1
500
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2016-03-08T09:45:52Z
2016-03-08T09:45:52Z
2014
Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4⁺ memory T Cells. 2014, 5:5407 Nat Commun
2041-1723
25382623
10.1038/ncomms6407
http://hdl.handle.net/10033/600844
Nature communications
In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4(+) T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. Here we provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory (TSCM) CD4(+) T cells). This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the TSCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies.
en
Anti-Retroviral Agents
CD4-Positive T-Lymphocytes
Cell Differentiation
Cohort Studies
Cross-Sectional Studies
Disease Progression
Disease Reservoirs
HIV Infections
HIV-1
Humans
T-Lymphocyte Subsets
Time Factors
Viral Load
Virus Latency
Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4⁺ memory T Cells.
Article
2018-06-13T20:04:26Z
In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4(+) T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. Here we provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory (TSCM) CD4(+) T cells). This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the TSCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies.
ORIGINAL
Jaafoura et al.pdf
Jaafoura et al.pdf
Open Access article
application/pdf
680632
https://hzi.openrepository.com/bitstream/10033/600844/1/Jaafoura%20et%20al.pdf
8bf9cbfb7f9c19e231cdf0f9ac7df44d
MD5
1
true
Supplement .pdf
Supplement .pdf
supplemental information
application/pdf
522836
https://hzi.openrepository.com/bitstream/10033/600844/2/Supplement%20.pdf
605b07676e20d6a7e4b94f65655f4992
MD5
2
false
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/600844/3/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
3
false
license_text
license_text
application/octet-stream
22333
https://hzi.openrepository.com/bitstream/10033/600844/4/license_text
33af6f23fea3b848a02227818b46d2ee
MD5
4
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/600844/5/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
5
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/600844/6/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
6
false
TEXT
Jaafoura et al.pdf.txt
Jaafoura et al.pdf.txt
Extracted Text
text/plain
46245
https://hzi.openrepository.com/bitstream/10033/600844/7/Jaafoura%20et%20al.pdf.txt
cc20ae7db36e38b7ad2d11407b67f687
MD5
7
false
Supplement .pdf.txt
Supplement .pdf.txt
Extracted Text
text/plain
8585
https://hzi.openrepository.com/bitstream/10033/600844/9/Supplement%20.pdf.txt
b0b3237dfc9800e953e7d8dadc962d2e
MD5
9
false
THUMBNAIL
Jaafoura et al.pdf.jpg
Jaafoura et al.pdf.jpg
Generated Thumbnail
image/jpeg
63135
https://hzi.openrepository.com/bitstream/10033/600844/11/Jaafoura%20et%20al.pdf.jpg
9e67699f9c03b2f70ef54d77e118c0e5
MD5
11
false
Supplement .pdf.jpg
Supplement .pdf.jpg
Generated Thumbnail
image/jpeg
36211
https://hzi.openrepository.com/bitstream/10033/600844/12/Supplement%20.pdf.jpg
5c2caa001dca7e150a5f03f3ea4276f0
MD5
12
false
10033/600844
oai:hzi.openrepository.com:10033/600844
2019-08-30 11:26:42.841
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6009432019-08-30T11:26:12Zcom_10033_620659col_10033_620660
Binder, Sebastian C
ca9fc32341dea761712a6ca7f0d7308b
600
http://orcid.org/0000-0003-1169-1786
Eckweiler, Denitsa
7f94e4a97acbbd6d6489b73dac2e62a3
500
Schulz, Sebastian
ff6eac0cf610ab75a1b7b352f76be4e3
500
Bielecka, Agata
d62a2afeda8a8d70ab959c9179fb8f45
500
Nicolai, Tanja
30ab7b6a3c5c7a2f8e2f07b0d8646fef
500
Franke, Raimo
220869c17f78c4a162832f3e32aeafbc
500
Häussler, Susanne
d2527fb005be9775f94b5de7f3de1fbf
500
Müller, A
9b8ad34dbc3a1fe389350bd24d0d473c
500
Helmholtz Centre for infection research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.
2016-03-08T15:02:28Z
2016-03-08T15:02:28Z
2016
Functional modules of sigma factor regulons guarantee adaptability and evolvability. 2016, 6:22212 Sci Rep
2045-2322
26915971
10.1038/srep22212
http://hdl.handle.net/10033/600943
Scientific reports
The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.
en
Functional modules of sigma factor regulons guarantee adaptability and evolvability.
Article
2018-06-13T21:36:49Z
The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.
ORIGINAL
Binder et al.pdf
Binder et al.pdf
Open Access publication
application/pdf
1092392
https://hzi.openrepository.com/bitstream/10033/600943/1/Binder%20et%20al.pdf
a61a9b4aadd165e1f34d0bb36747f886
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/600943/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
22333
https://hzi.openrepository.com/bitstream/10033/600943/3/license_text
33af6f23fea3b848a02227818b46d2ee
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/600943/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/600943/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Binder et al.pdf.txt
Binder et al.pdf.txt
Extracted Text
text/plain
54409
https://hzi.openrepository.com/bitstream/10033/600943/6/Binder%20et%20al.pdf.txt
f64df1f845a5e34120c340a7cffe6d12
MD5
6
false
THUMBNAIL
Binder et al.pdf.jpg
Binder et al.pdf.jpg
Generated Thumbnail
image/jpeg
114564
https://hzi.openrepository.com/bitstream/10033/600943/7/Binder%20et%20al.pdf.jpg
6e2cc1e7ffd075267509f5acd123db7f
MD5
7
false
10033/600943
oai:hzi.openrepository.com:10033/600943
2019-08-30 11:26:12.939
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6091252019-08-30T11:31:23Zcom_10033_620659col_10033_620660
Tas, Jeroen M J
2c028d924d3a9b28142ba8f151250f29
500
Mesin, Luka
1c119fe8cd293f8150f01ecb915d84ff
500
Pasqual, Giulia
3d1a2d7392ed9a96a5fd6bc98acd0720
500
Targ, Sasha
fb43b15054564a93da5dd3cb64fc5995
500
Jacobsen, Johanne T
89ddc4dbc4e4b54f6f2243440cfa14ab
500
Mano, Yasuko M
990a3da0ff8eeb5d24cfd60c0fe65c02
500
Chen, Casie S
0c080d0b212d84fafee4fbf11db2e47e
500
Weill, Jean-Claude
5916488565ab3762545214a2d0694c05
500
Reynaud, Claude-Agnès
cf02fe06d496a7138f4c41a503e6eab3
500
Browne, Edward P
14c15daa7aa3c97d68398eea8b1c522a
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Victora, Gabriel D
f5d6a01775ef0b0c513db3746e04ee8d
500
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
2016-05-12T08:09:36Z
2016-05-12T08:09:36Z
2016-03-04
Visualizing antibody affinity maturation in germinal centers. 2016, 351 (6277):1048-54 Science
1095-9203
26912368
10.1126/science.aad3439
http://hdl.handle.net/10033/609125
Science (New York, N.Y.)
Antibodies somatically mutate to attain high affinity in germinal centers (GCs). There, competition between B cell clones and among somatic mutants of each clone drives an increase in average affinity across the population. The extent to which higher-affinity cells eliminating competitors restricts clonal diversity is unknown. By combining multiphoton microscopy and sequencing, we show that tens to hundreds of distinct B cell clones seed each GC and that GCs lose clonal diversity at widely disparate rates. Furthermore, efficient affinity maturation can occur in the absence of homogenizing selection, ensuring that many clones can mature in parallel within the same GC. Our findings have implications for development of vaccines in which antibodies with nonimmunodominant specificities must be elicited, as is the case for HIV-1 and influenza.
en
Animals
Antibodies
Antibody Affinity
B-Lymphocytes
Germinal Center
HIV-1
Humans
Mice
Microscopy, Fluorescence, Multiphoton
Molecular Imaging
Orthomyxoviridae
Sequence Analysis, DNA
Single-Cell Analysis
Visualizing antibody affinity maturation in germinal centers.
Article
2016-08-15T00:00:00Z
Antibodies somatically mutate to attain high affinity in germinal centers (GCs). There, competition between B cell clones and among somatic mutants of each clone drives an increase in average affinity across the population. The extent to which higher-affinity cells eliminating competitors restricts clonal diversity is unknown. By combining multiphoton microscopy and sequencing, we show that tens to hundreds of distinct B cell clones seed each GC and that GCs lose clonal diversity at widely disparate rates. Furthermore, efficient affinity maturation can occur in the absence of homogenizing selection, ensuring that many clones can mature in parallel within the same GC. Our findings have implications for development of vaccines in which antibodies with nonimmunodominant specificities must be elicited, as is the case for HIV-1 and influenza.
ORIGINAL
Tas et al.pdf
Tas et al.pdf
original manuscript
application/pdf
244578
https://hzi.openrepository.com/bitstream/10033/609125/1/Tas%20et%20al.pdf
fda4368cc93f92de0a7645272da64d65
MD5
1
true
Supplement.pdf
Supplement.pdf
supplemental materials
application/pdf
26904145
https://hzi.openrepository.com/bitstream/10033/609125/2/Supplement.pdf
c6a9190fb36752f83fe4ddee49509ac3
MD5
2
false
DatabaseS1.xlsx
DatabaseS1.xlsx
supplemental database
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
417429
https://hzi.openrepository.com/bitstream/10033/609125/3/DatabaseS1.xlsx
a00492b28e9a87f065f2f4354a848d4d
MD5
3
false
Figure1.jpg
Figure1.jpg
figure 1
image/jpeg
2759171
https://hzi.openrepository.com/bitstream/10033/609125/4/Figure1.jpg
4690f697cd935de5e302b4bf3db2aa00
MD5
4
false
Figure2.jpg
Figure2.jpg
figure 2
image/jpeg
1465570
https://hzi.openrepository.com/bitstream/10033/609125/5/Figure2.jpg
738da19e4528f31c07fcc4a8ee5ecfb1
MD5
5
false
Figure3.jpg
Figure3.jpg
figure 3
image/jpeg
2902630
https://hzi.openrepository.com/bitstream/10033/609125/6/Figure3.jpg
8b7395aa8a25d58936a4d0de739f91b0
MD5
6
false
Figure4.jpg
Figure4.jpg
figure 4
image/jpeg
2324450
https://hzi.openrepository.com/bitstream/10033/609125/7/Figure4.jpg
85f884dfea1c96a80023f74d298591c1
MD5
7
false
Figure5.jpg
Figure5.jpg
figure 5
image/jpeg
1391773
https://hzi.openrepository.com/bitstream/10033/609125/8/Figure5.jpg
128e6c90b3d600e4b7a64ce013d8ffd4
MD5
8
false
MovieS1.mp4
MovieS1.mp4
supplemental movie 1
application/octet-stream
4412984
https://hzi.openrepository.com/bitstream/10033/609125/9/MovieS1.mp4
eb8e4a06dd6883068a2fa6f059b48466
MD5
9
false
MovieS2.mp4
MovieS2.mp4
supplemental movie 2
application/octet-stream
4536067
https://hzi.openrepository.com/bitstream/10033/609125/10/MovieS2.mp4
054daa29bb47d646e8acb54f4bad1a75
MD5
10
false
MovieS3.mp4
MovieS3.mp4
supplemental movie 3
application/octet-stream
3803357
https://hzi.openrepository.com/bitstream/10033/609125/11/MovieS3.mp4
59ae73e5b301c7ebdfd1679466336db8
MD5
11
false
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/609125/12/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
12
false
license_text
license_text
application/octet-stream
22333
https://hzi.openrepository.com/bitstream/10033/609125/13/license_text
33af6f23fea3b848a02227818b46d2ee
MD5
13
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/609125/14/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
14
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/609125/15/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
15
false
TEXT
Tas et al.pdf.txt
Tas et al.pdf.txt
Extracted Text
text/plain
41847
https://hzi.openrepository.com/bitstream/10033/609125/16/Tas%20et%20al.pdf.txt
29bea8b2e2457be2f7489b5f94d8df2a
MD5
16
false
Supplement.pdf.txt
Supplement.pdf.txt
Extracted Text
text/plain
47454
https://hzi.openrepository.com/bitstream/10033/609125/18/Supplement.pdf.txt
88e4ca8a89422f315c311a10932dc59e
MD5
18
false
DatabaseS1.xlsx.txt
DatabaseS1.xlsx.txt
Extracted text
text/plain
911411
https://hzi.openrepository.com/bitstream/10033/609125/20/DatabaseS1.xlsx.txt
6e887508c3d970eba124a470e2105858
MD5
20
false
THUMBNAIL
Figure1.jpg.jpg
Figure1.jpg.jpg
Generated Thumbnail
image/jpeg
11825
https://hzi.openrepository.com/bitstream/10033/609125/21/Figure1.jpg.jpg
808180df275c63e40705a70dffcf82df
MD5
21
false
Figure2.jpg.jpg
Figure2.jpg.jpg
Generated Thumbnail
image/jpeg
10662
https://hzi.openrepository.com/bitstream/10033/609125/22/Figure2.jpg.jpg
53bdea505e0de82743e67f05b4b77213
MD5
22
false
Figure3.jpg.jpg
Figure3.jpg.jpg
Generated Thumbnail
image/jpeg
11241
https://hzi.openrepository.com/bitstream/10033/609125/23/Figure3.jpg.jpg
b3201ae97930ba64f542f506075823d8
MD5
23
false
Figure4.jpg.jpg
Figure4.jpg.jpg
Generated Thumbnail
image/jpeg
15577
https://hzi.openrepository.com/bitstream/10033/609125/24/Figure4.jpg.jpg
a6f10135b9ec25c86c35e471db7b6fdc
MD5
24
false
Figure5.jpg.jpg
Figure5.jpg.jpg
Generated Thumbnail
image/jpeg
9948
https://hzi.openrepository.com/bitstream/10033/609125/25/Figure5.jpg.jpg
238b65015bfa1e146d8798d1e852a3d0
MD5
25
false
Tas et al.pdf.jpg
Tas et al.pdf.jpg
Generated Thumbnail
image/jpeg
40372
https://hzi.openrepository.com/bitstream/10033/609125/30/Tas%20et%20al.pdf.jpg
bb4229b8fbec2931a4b7f905df3cbd5b
MD5
30
false
Supplement.pdf.jpg
Supplement.pdf.jpg
Generated Thumbnail
image/jpeg
29816
https://hzi.openrepository.com/bitstream/10033/609125/31/Supplement.pdf.jpg
015feafec347806708ee84743b3fb7e5
MD5
31
false
DatabaseS1.xlsx.jpg
DatabaseS1.xlsx.jpg
Generated Thumbnail
image/jpeg
98287
https://hzi.openrepository.com/bitstream/10033/609125/32/DatabaseS1.xlsx.jpg
9e2f9dee3dd8a5352447ce1f8bb5aaa0
MD5
32
false
CONVERTED2_2939310
10033/609125
oai:hzi.openrepository.com:10033/609125
2019-08-30 11:31:23.463
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6104362019-08-30T11:30:32Zcom_10033_620659col_10033_620660
Kempf, Harald
d0df9fa985907043b0f780c9f1c89d59
500
Bleicher, Marcus
93411718ba96ac2e26a30be25b6fc923
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2016-05-20T11:41:31Z
2016-05-20T11:41:31Z
2015
Spatio-Temporal Dynamics of Hypoxia during Radiotherapy. 2015, 10 (8):e0133357 PLoS ONE
1932-6203
26273841
10.1371/journal.pone.0133357
http://hdl.handle.net/10033/610436
PloS one
Tumour hypoxia plays a pivotal role in cancer therapy for most therapeutic approaches from radiotherapy to immunotherapy. The detailed and accurate knowledge of the oxygen distribution in a tumour is necessary in order to determine the right treatment strategy. Still, due to the limited spatial and temporal resolution of imaging methods as well as lacking fundamental understanding of internal oxygenation dynamics in tumours, the precise oxygen distribution map is rarely available for treatment planing. We employ an agent-based in silico tumour spheroid model in order to study the complex, localized and fast oxygen dynamics in tumour micro-regions which are induced by radiotherapy. A lattice-free, 3D, agent-based approach for cell representation is coupled with a high-resolution diffusion solver that includes a tissue density-dependent diffusion coefficient. This allows us to assess the space- and time-resolved reoxygenation response of a small subvolume of tumour tissue in response to radiotherapy. In response to irradiation the tumour nodule exhibits characteristic reoxygenation and re-depletion dynamics which we resolve with high spatio-temporal resolution. The reoxygenation follows specific timings, which should be respected in treatment in order to maximise the use of the oxygen enhancement effects. Oxygen dynamics within the tumour create windows of opportunity for the use of adjuvant chemotherapeutica and hypoxia-activated drugs. Overall, we show that by using modelling it is possible to follow the oxygenation dynamics beyond common resolution limits and predict beneficial strategies for therapy and in vitro verification. Models of cell cycle and oxygen dynamics in tumours should in the future be combined with imaging techniques, to allow for a systematic experimental study of possible improved schedules and to ultimately extend the reach of oxygenation monitoring available in clinical treatment.
en
Animals
Cell Hypoxia
Cell Line, Tumor
Models, Theoretical
Radiotherapy
Spatio-Temporal Dynamics of Hypoxia during Radiotherapy.
Article
2018-06-12T21:49:59Z
Tumour hypoxia plays a pivotal role in cancer therapy for most therapeutic approaches from radiotherapy to immunotherapy. The detailed and accurate knowledge of the oxygen distribution in a tumour is necessary in order to determine the right treatment strategy. Still, due to the limited spatial and temporal resolution of imaging methods as well as lacking fundamental understanding of internal oxygenation dynamics in tumours, the precise oxygen distribution map is rarely available for treatment planing. We employ an agent-based in silico tumour spheroid model in order to study the complex, localized and fast oxygen dynamics in tumour micro-regions which are induced by radiotherapy. A lattice-free, 3D, agent-based approach for cell representation is coupled with a high-resolution diffusion solver that includes a tissue density-dependent diffusion coefficient. This allows us to assess the space- and time-resolved reoxygenation response of a small subvolume of tumour tissue in response to radiotherapy. In response to irradiation the tumour nodule exhibits characteristic reoxygenation and re-depletion dynamics which we resolve with high spatio-temporal resolution. The reoxygenation follows specific timings, which should be respected in treatment in order to maximise the use of the oxygen enhancement effects. Oxygen dynamics within the tumour create windows of opportunity for the use of adjuvant chemotherapeutica and hypoxia-activated drugs. Overall, we show that by using modelling it is possible to follow the oxygenation dynamics beyond common resolution limits and predict beneficial strategies for therapy and in vitro verification. Models of cell cycle and oxygen dynamics in tumours should in the future be combined with imaging techniques, to allow for a systematic experimental study of possible improved schedules and to ultimately extend the reach of oxygenation monitoring available in clinical treatment.
ORIGINAL
Kempf et al.PDF
Kempf et al.PDF
Open Access publication
application/pdf
6198030
https://hzi.openrepository.com/bitstream/10033/610436/1/Kempf%20et%20al.PDF
69062075fad893ac866dee6f2709e023
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/610436/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
22333
https://hzi.openrepository.com/bitstream/10033/610436/3/license_text
33af6f23fea3b848a02227818b46d2ee
MD5
3
false
license_rdf
license_rdf
application/octet-stream
23748
https://hzi.openrepository.com/bitstream/10033/610436/4/license_rdf
b92763cfc0af52c7c868455edfaf3266
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/610436/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Kempf et al.PDF.txt
Kempf et al.PDF.txt
Extracted Text
text/plain
82578
https://hzi.openrepository.com/bitstream/10033/610436/6/Kempf%20et%20al.PDF.txt
8c8f899e7af71930d95ad6537fe15c66
MD5
6
false
THUMBNAIL
Kempf et al.PDF.jpg
Kempf et al.PDF.jpg
Generated Thumbnail
image/jpeg
96554
https://hzi.openrepository.com/bitstream/10033/610436/7/Kempf%20et%20al.PDF.jpg
e49481fc851d12c788d322a2510c4ebb
MD5
7
false
10033/610436
oai:hzi.openrepository.com:10033/610436
2019-08-30 11:30:32.143
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6169322019-08-30T11:33:29Zcom_10033_620659col_10033_620660
Halle, Stephan
08506b772c0146cd365008838a3ef2b6
500
Keyser, Kirsten Anja
b9cd6307d8cb7efde16fe6ad059f9c78
500
Stahl, Felix Rolf
a48be9fa2f88574dcea1327814556004
500
Busche, Andreas
04322e80c4749196fb556c6220dd4abf
500
Marquardt, Anja
12605f59767be766125f31fef4dcf788
500
Zheng, Xiang
84cffd083e00a1b033771336aeab1722
500
Galla, Melanie
38e5bd4e53747be3dc0e202a2987d4a2
500
Heissmeyer, Vigo
83265c69c980a99ff5d0003d7aa7e3a3
500
Heller, Katrin
080901382a7cd2276142f764a6c1a136
500
Boelter, Jasmin
985b84f875926199733d6b6eac41a19b
500
Wagner, Karen
94b3de433219471baf484f1ac5b65089
500
Bischoff, Yvonne
210ac1fd0e93660643cb73155af20304
500
Martens, Rieke
eb79547061fddea8f6478aefa8b9dbeb
500
Braun, Asolina
59764827eeae3aa19b2ab0c309d0c51a
500
Werth, Kathrin
f17b7eb3e3dbf16083d09edab0c2e1dc
500
Uvarovskii, Alexey
b290333ebc122afd16e4929acc6186d3
500
Kempf, Harald
d0df9fa985907043b0f780c9f1c89d59
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Arens, Ramon
154af7271efcba245d34a07477428eb8
500
Kremer, Melanie
6fffe142c2f28fc71b31674cf8cf237f
500
Sutter, Gerd
f701add92288778b1b06f1d6b6d6200c
500
Messerle, Martin
f32ed852de2e0307d35955c90176a6c1
500
Förster, Reinhold
df49c6ec78650b8a9e20137d6e37aa68
500
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2016-07-14T10:56:31Z
2016-07-14T10:56:31Z
2016-02-16
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. 2016, 44 (2):233-45 Immunity
1097-4180
26872694
10.1016/j.immuni.2016.01.010
http://hdl.handle.net/10033/616932
Immunity
According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL)-mediated killing of virus-infected cells in vivo remains elusive. We used two-photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2-16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8(+) T cell immunity.
en
nfo:eu-repo/grantAgreement/EC/FP7/322645
openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Animals
Calcium Signaling
Cell Communication
Cells, Cultured
Cytotoxicity, Immunologic
Herpesviridae Infections
Humans
Immune Evasion
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Fluorescence, Multiphoton
Muromegalovirus
Perforin
T-Lymphocyte Subsets
T-Lymphocytes, Cytotoxic
Vaccinia
Vaccinia virus
In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
Article
2018-06-13T01:35:39Z
According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL)-mediated killing of virus-infected cells in vivo remains elusive. We used two-photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2-16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8(+) T cell immunity.
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/616932/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
ORIGINAL
Halle et al.pdf
Halle et al.pdf
Open Access article
application/pdf
4041826
https://hzi.openrepository.com/bitstream/10033/616932/1/Halle%20et%20al.pdf
842a5bb877e41d4cb81db5a810ead76c
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/616932/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/616932/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/616932/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
TEXT
Halle et al.pdf.txt
Halle et al.pdf.txt
Extracted Text
text/plain
63924
https://hzi.openrepository.com/bitstream/10033/616932/6/Halle%20et%20al.pdf.txt
2beb29459d85b4cc6fae451fc650a76c
MD5
6
false
THUMBNAIL
Halle et al.pdf.jpg
Halle et al.pdf.jpg
Generated Thumbnail
image/jpeg
77245
https://hzi.openrepository.com/bitstream/10033/616932/7/Halle%20et%20al.pdf.jpg
a885e41af5e54f9ffee23ba66a1cbda6
MD5
7
false
elsevier-thumbnail.png
application/octet-stream
37582
https://hzi.openrepository.com/bitstream/10033/616932/8/elsevier-thumbnail.png
c6f3a3d7b96530d0d972dcf8900e04ee
MD5
8
false
10033/616932
oai:hzi.openrepository.com:10033/616932
2019-08-30 11:33:29.878
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6205622019-08-30T11:30:58Zcom_10033_620659col_10033_620660
Sukhorukov, Valerii M
d912af8288a8ca7e0fa2e59f10bc2250
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2016-10-21T14:09:24Z
2016-10-21T14:09:24Z
2015
Structural Heterogeneity of Mitochondria Induced by the Microtubule Cytoskeleton. 2015, 5:13924 Sci Rep
2045-2322
26355039
10.1038/srep13924
http://hdl.handle.net/10033/620562
Scientific reports
By events of fusion and fission mitochondria generate a partially interconnected, irregular network of poorly specified architecture. Here, its organization is examined theoretically by taking into account the physical association of mitochondria with microtubules. Parameters of the cytoskeleton mesh are derived from the mechanics of single fibers. The model of the mitochondrial reticulum is formulated in terms of a dynamic spatial graph. The graph dynamics is modulated by the density of microtubules and their crossings. The model reproduces the full spectrum of experimentally found mitochondrial configurations. In centrosome-organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery. An integrated analysis of the cytoskeletal and the mitochondrial components reveals that the structure of the reticulum depends on the balance between anterograde and retrograde motility of mitochondria on microtubules, in addition to fission and fusion. We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Structural Heterogeneity of Mitochondria Induced by the Microtubule Cytoskeleton.
Article
2018-06-13T03:54:14Z
By events of fusion and fission mitochondria generate a partially interconnected, irregular network of poorly specified architecture. Here, its organization is examined theoretically by taking into account the physical association of mitochondria with microtubules. Parameters of the cytoskeleton mesh are derived from the mechanics of single fibers. The model of the mitochondrial reticulum is formulated in terms of a dynamic spatial graph. The graph dynamics is modulated by the density of microtubules and their crossings. The model reproduces the full spectrum of experimentally found mitochondrial configurations. In centrosome-organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery. An integrated analysis of the cytoskeletal and the mitochondrial components reveals that the structure of the reticulum depends on the balance between anterograde and retrograde motility of mitochondria on microtubules, in addition to fission and fusion. We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation.
ORIGINAL
Sukhorukov and Meyer-Hermann.pdf
Sukhorukov and Meyer-Hermann.pdf
Open Access publication
application/pdf
1106192
https://hzi.openrepository.com/bitstream/10033/620562/1/Sukhorukov%20and%20Meyer-Hermann.pdf
a09ea5d4645279d1d8b750dec64f61ed
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/620562/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620562/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620562/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/620562/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Sukhorukov and Meyer-Hermann.pdf.txt
Sukhorukov and Meyer-Hermann.pdf.txt
Extracted Text
text/plain
60325
https://hzi.openrepository.com/bitstream/10033/620562/6/Sukhorukov%20and%20Meyer-Hermann.pdf.txt
fe2c8a7e765e58d0d5731b43eb72622f
MD5
6
false
THUMBNAIL
Sukhorukov and Meyer-Hermann.pdf.jpg
Sukhorukov and Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
103874
https://hzi.openrepository.com/bitstream/10033/620562/7/Sukhorukov%20and%20Meyer-Hermann.pdf.jpg
ff735462d883cf4051353ef3b9225b36
MD5
7
false
10033/620562
oai:hzi.openrepository.com:10033/620562
2019-08-30 11:30:58.346
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6205432019-08-30T11:34:48Zcom_10033_620659col_10033_620660
Marschall, Andrea L J
4f0f7c9b639bafaaa9d2fae177f6c1e2
500
Dübel, Stefan
ed269bc301d0c4d6bd191baa917eb8a9
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2016-10-07T13:15:15Z
2016-10-07T13:15:15Z
2016
Antibodies inside of a cell can change its outside: Can intrabodies provide a new therapeutic paradigm? 2016, 14:304-8 Comput Struct Biotechnol J
2001-0370
27570612
10.1016/j.csbj.2016.07.003
http://hdl.handle.net/10033/620543
Computational and structural biotechnology journal
Challenges posed by complex diseases such as cancer, chronic viral infections, neurodegenerative disorders and many others have forced researchers to think beyond classic small molecule drugs, exploring new therapeutic strategies such as therapy with RNAi, CRISPR/Cas9 or antibody therapies as single or as combination therapies with existing drugs. While classic antibody therapies based on parenteral application can only reach extracellular targets, intracellular application of antibodies could provide specific advantages but is so far little recognized in translational research. Intrabodies allow high specificity and targeting of splice variants or post translational modifications. At the same time off target effects can be minimized by thorough biochemical characterization. Knockdown of cellular proteins by intrabodies has been reported for a significant number of disease-relevant targets, including ErbB-2, EGFR, VEGFR-2, Metalloproteinase MMP2 and MMP9, β-amyloid protein, α-synuclein, HIV gp120, HCV core and many others. This review outlines the recent advances in ER intrabody technology and their potential use in therapy.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Antibodies inside of a cell can change its outside: Can intrabodies provide a new therapeutic paradigm?
Article
2018-06-12T17:54:07Z
Challenges posed by complex diseases such as cancer, chronic viral infections, neurodegenerative disorders and many others have forced researchers to think beyond classic small molecule drugs, exploring new therapeutic strategies such as therapy with RNAi, CRISPR/Cas9 or antibody therapies as single or as combination therapies with existing drugs. While classic antibody therapies based on parenteral application can only reach extracellular targets, intracellular application of antibodies could provide specific advantages but is so far little recognized in translational research. Intrabodies allow high specificity and targeting of splice variants or post translational modifications. At the same time off target effects can be minimized by thorough biochemical characterization. Knockdown of cellular proteins by intrabodies has been reported for a significant number of disease-relevant targets, including ErbB-2, EGFR, VEGFR-2, Metalloproteinase MMP2 and MMP9, β-amyloid protein, α-synuclein, HIV gp120, HCV core and many others. This review outlines the recent advances in ER intrabody technology and their potential use in therapy.
ORIGINAL
Marshall and Dübel.pdf
Marshall and Dübel.pdf
Open Access publication
application/pdf
541714
https://hzi.openrepository.com/bitstream/10033/620543/1/Marshall%20and%20D%c3%bcbel.pdf
6c4f586e8f20f6e5a5e4c67b52ca2a56
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/620543/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620543/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620543/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/620543/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Marshall and Dübel.pdf.txt
Marshall and Dübel.pdf.txt
Extracted Text
text/plain
34105
https://hzi.openrepository.com/bitstream/10033/620543/6/Marshall%20and%20D%c3%bcbel.pdf.txt
44425842c799c064662990922469c6a2
MD5
6
false
THUMBNAIL
Marshall and Dübel.pdf.jpg
Marshall and Dübel.pdf.jpg
Generated Thumbnail
image/jpeg
115093
https://hzi.openrepository.com/bitstream/10033/620543/7/Marshall%20and%20D%c3%bcbel.pdf.jpg
eb94ba282d35f7f56ce67f645c7e0f74
MD5
7
false
elsevier-thumbnail.png
application/octet-stream
49430
https://hzi.openrepository.com/bitstream/10033/620543/8/elsevier-thumbnail.png
ddbbe0e3e633dfe008a8ce069b8df439
MD5
8
false
10033/620543
oai:hzi.openrepository.com:10033/620543
2019-08-30 11:34:48.244
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6205462019-08-30T11:35:39Zcom_10033_620659col_10033_620660
Alfonso, J C L
896385bb2f19a731862f77b3c56a717d
500
Schaadt, N S
ad8e415ad876bbff49f2e727b2de8559
500
Schönmeyer, R
bac8bed8921d9ee9035d1fbf935241e7
500
Brieu, N
755e22d6cd5b57b3a8630321a2277fca
500
Forestier, G
0e8a48f530ea90f189e7cfd0915b9d11
500
Wemmert, C
d3e7c7f0f3100a12e27c57c9bd6ca2fb
500
Feuerhake, F
59898c49344e9b1cc676dce57e0297a9
500
Hatzikirou, H
32b9e34beb5f7b9e23a066cf51d460df
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2016-10-12T07:54:50Z
2016-10-12T07:54:50Z
2016-10-12
In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium., 6:33322 Sci Rep
2045-2322
27659691
10.1038/srep33322
http://hdl.handle.net/10033/620546
Scientific reports
Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches.
ENG
en_US
http://creativecommons.org/licenses/by-nc-sa/4.0/
In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium.
Article
2018-06-13T16:03:28Z
Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches.
ORIGINAL
Alfonso et al.pdf
Alfonso et al.pdf
Open Access publication
application/pdf
4665571
https://hzi.openrepository.com/bitstream/10033/620546/1/Alfonso%20et%20al.pdf
10acdce38e9891bf6d27741dae952c06
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/620546/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620546/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620546/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/620546/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Alfonso et al.pdf.txt
Alfonso et al.pdf.txt
Extracted Text
text/plain
81425
https://hzi.openrepository.com/bitstream/10033/620546/6/Alfonso%20et%20al.pdf.txt
9107fd88ba72663e18f54c520928540d
MD5
6
false
THUMBNAIL
Alfonso et al.pdf.jpg
Alfonso et al.pdf.jpg
Generated Thumbnail
image/jpeg
109814
https://hzi.openrepository.com/bitstream/10033/620546/7/Alfonso%20et%20al.pdf.jpg
b282dfece42044038195d0fe8d630910
MD5
7
false
10033/620546
oai:hzi.openrepository.com:10033/620546
2019-08-30 11:35:39.484
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6206622019-08-30T11:36:05Zcom_10033_620659col_10033_620660
Alfonso, J C L
896385bb2f19a731862f77b3c56a717d
500
Köhn-Luque, A
f0c60c35f74646788f43ccf73b7c9aa2
500
Stylianopoulos, T
aac08ab6204da1978eb975c389e136a2
500
Feuerhake, F
59898c49344e9b1cc676dce57e0297a9
500
Deutsch, A
e47a1b66028665186c7b8948ae70fa4b
500
Hatzikirou, H
32b9e34beb5f7b9e23a066cf51d460df
500
Braunschweiger zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2016-12-12T12:36:32Z
2016-12-12T12:36:32Z
2016-11-23
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights. 2016, 6:37283 Sci Rep
2045-2322
27876890
10.1038/srep37283
http://hdl.handle.net/10033/620662
Scientific reports
Gliomas are highly invasive brain tumours characterised by poor prognosis and limited response to therapy. There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve tumour blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation induced by blood vessel occlusion/collapse. In contrast, the therapeutic intention of normalising the abnormal tumour vasculature is to improve the efficacy of conventional treatment modalities. Although these strategies have shown therapeutic potential, it remains unclear why they both often fail to control glioma growth. To shed some light on this issue, we propose a mathematical model based on the migration/proliferation dichotomy of glioma cells in order to investigate why vaso-modulatory interventions have shown limited success in terms of tumour clearance. We found the existence of a critical cell proliferation/diffusion ratio that separates glioma responses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the front speed and increase the infiltration width, for those in the other regime, the invasion speed increases and infiltration width decreases. We discuss how these in silico findings can be used to guide individualised vaso-modulatory approaches to improve treatment success rates.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights.
Article
2018-06-13T09:25:24Z
Gliomas are highly invasive brain tumours characterised by poor prognosis and limited response to therapy. There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve tumour blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation induced by blood vessel occlusion/collapse. In contrast, the therapeutic intention of normalising the abnormal tumour vasculature is to improve the efficacy of conventional treatment modalities. Although these strategies have shown therapeutic potential, it remains unclear why they both often fail to control glioma growth. To shed some light on this issue, we propose a mathematical model based on the migration/proliferation dichotomy of glioma cells in order to investigate why vaso-modulatory interventions have shown limited success in terms of tumour clearance. We found the existence of a critical cell proliferation/diffusion ratio that separates glioma responses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the front speed and increase the infiltration width, for those in the other regime, the invasion speed increases and infiltration width decreases. We discuss how these in silico findings can be used to guide individualised vaso-modulatory approaches to improve treatment success rates.
ORIGINAL
Alfonso et al.pdf
Alfonso et al.pdf
Open Access publication
application/pdf
4665571
https://hzi.openrepository.com/bitstream/10033/620662/1/Alfonso%20et%20al.pdf
10acdce38e9891bf6d27741dae952c06
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/620662/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620662/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620662/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/620662/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Alfonso et al.pdf.txt
Alfonso et al.pdf.txt
Extracted Text
text/plain
81425
https://hzi.openrepository.com/bitstream/10033/620662/6/Alfonso%20et%20al.pdf.txt
9107fd88ba72663e18f54c520928540d
MD5
6
false
THUMBNAIL
Alfonso et al.pdf.jpg
Alfonso et al.pdf.jpg
Generated Thumbnail
image/jpeg
109814
https://hzi.openrepository.com/bitstream/10033/620662/7/Alfonso%20et%20al.pdf.jpg
b282dfece42044038195d0fe8d630910
MD5
7
false
10033/620662
oai:hzi.openrepository.com:10033/620662
2019-08-30 11:36:05.122
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6206682019-08-30T11:35:39Zcom_10033_620659col_10033_620660
Montaseri, Ghazal
0188311a96861e58b03f0dde1e12040f
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2016-12-15T12:58:39Z
2016-12-15T12:58:39Z
2016-10
Diversity of coupled oscillators can enhance their synchronization. 2016, 94 (4-1):042213 Phys Rev E
2470-0053
27841630
10.1103/PhysRevE.94.042213
http://hdl.handle.net/10033/620668
Physical review. E
The heterogeneity of coupled oscillators is important for the degree of their synchronization. According to the classical Kuramoto model, larger heterogeneity reduces synchronization. Here, we show that in a model for coupled pancreatic β-cells, higher diversity of the cells induces higher synchrony. We find that any system of coupled oscillators that oscillates on two time scales and in which heterogeneity causes a transition from chaotic to damped oscillations on the fast time scale exhibits this property. Thus, synchronization of a subset of oscillating systems can be enhanced by increasing the heterogeneity of the system constituents.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Diversity of coupled oscillators can enhance their synchronization.
Article
2018-06-13T00:48:39Z
The heterogeneity of coupled oscillators is important for the degree of their synchronization. According to the classical Kuramoto model, larger heterogeneity reduces synchronization. Here, we show that in a model for coupled pancreatic β-cells, higher diversity of the cells induces higher synchrony. We find that any system of coupled oscillators that oscillates on two time scales and in which heterogeneity causes a transition from chaotic to damped oscillations on the fast time scale exhibits this property. Thus, synchronization of a subset of oscillating systems can be enhanced by increasing the heterogeneity of the system constituents.
ORIGINAL
Montaeri and Meyer-Hermann.pdf
Montaeri and Meyer-Hermann.pdf
allowed publisher's PDF
application/pdf
2955427
https://hzi.openrepository.com/bitstream/10033/620668/1/Montaeri%20and%20Meyer-Hermann.pdf
1bb10b21881cf9ef243a3c2521052736
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/620668/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620668/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620668/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/620668/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Montaeri and Meyer-Hermann.pdf.txt
Montaeri and Meyer-Hermann.pdf.txt
Extracted Text
text/plain
46246
https://hzi.openrepository.com/bitstream/10033/620668/6/Montaeri%20and%20Meyer-Hermann.pdf.txt
e6aa100d48bc3577548067173457aefc
MD5
6
false
THUMBNAIL
Montaeri and Meyer-Hermann.pdf.jpg
Montaeri and Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
124371
https://hzi.openrepository.com/bitstream/10033/620668/7/Montaeri%20and%20Meyer-Hermann.pdf.jpg
0f6facaea8ff33c14719e14271ee6dec
MD5
7
false
10033/620668
oai:hzi.openrepository.com:10033/620668
2019-08-30 11:35:39.592
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6208142019-08-30T11:30:58Zcom_10033_620659col_10033_620660
Hatzikirou, H
32b9e34beb5f7b9e23a066cf51d460df
500
Alfonso, J C L
896385bb2f19a731862f77b3c56a717d
500
Mühle, S
3c74faf6c0e385993e69f4b33cc762c6
500
Stern, C
81b033b66e9aa8ed2153f6939351c86f
500
Weiss, S
cf2a616fa2c2a7f2df0a04aedc813538
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38124 Braunschweig, Germany.
2017-02-08T15:27:26Z
2017-02-08T15:27:26Z
2015-11-06
Cancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions. 2015, 12 (112) J R Soc Interface
1742-5662
26510827
10.1098/rsif.2015.0439
http://hdl.handle.net/10033/620814
Journal of the Royal Society, Interface
Currently, most of the basic mechanisms governing tumour-immune system interactions, in combination with modulations of tumour-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumour growth, where the main novelty is the modelling of the interplay between functional tumour vasculature and effector cell recruitment dynamics. Parameters are calibrated on the basis of different in vivo immunocompromised Rag1(-/-) and wild-type (WT) BALB/c murine tumour growth experiments. The model analysis supports that tumour vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immunostimulations. We find that improved levels of functional tumour vasculature, potentially mediated by normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumour burden reduction and growth control. Normalization of tumour blood vessels opens a therapeutic window of opportunity to augment the antitumour immune responses, as well as to reduce intratumoral immunosuppression and induced hypoxia due to vascular abnormalities. The potential success of normalizing tumour-associated vasculature closely depends on the effector cell recruitment dynamics and tumour sizes. Furthermore, an arbitrary increase in the initial effector cell concentration does not necessarily imply better tumour control. We evidence the existence of an optimal concentration range of effector cells for tumour shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immuno- and vasomodulatory interventions.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Animals
Mice
Mice, Inbred BALB C
Mice, Knockout
Models, Biological
Neoplasms, Experimental
Neovascularization, Pathologic
Cancer therapeutic potential of combinatorial immuno- and vasomodulatory interventions.
Article
2018-06-12T23:40:08Z
Currently, most of the basic mechanisms governing tumour-immune system interactions, in combination with modulations of tumour-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumour growth, where the main novelty is the modelling of the interplay between functional tumour vasculature and effector cell recruitment dynamics. Parameters are calibrated on the basis of different in vivo immunocompromised Rag1(-/-) and wild-type (WT) BALB/c murine tumour growth experiments. The model analysis supports that tumour vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immunostimulations. We find that improved levels of functional tumour vasculature, potentially mediated by normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumour burden reduction and growth control. Normalization of tumour blood vessels opens a therapeutic window of opportunity to augment the antitumour immune responses, as well as to reduce intratumoral immunosuppression and induced hypoxia due to vascular abnormalities. The potential success of normalizing tumour-associated vasculature closely depends on the effector cell recruitment dynamics and tumour sizes. Furthermore, an arbitrary increase in the initial effector cell concentration does not necessarily imply better tumour control. We evidence the existence of an optimal concentration range of effector cells for tumour shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immuno- and vasomodulatory interventions.
ORIGINAL
Hatzikirou et al.pdf
Hatzikirou et al.pdf
free PDF from the PubMed repository PMC
application/pdf
1085546
https://hzi.openrepository.com/bitstream/10033/620814/1/Hatzikirou%20et%20al.pdf
f4881769884aced5bc820a59cb5b633e
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/620814/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620814/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/620814/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/620814/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Hatzikirou et al.pdf.txt
Hatzikirou et al.pdf.txt
Extracted Text
text/plain
70855
https://hzi.openrepository.com/bitstream/10033/620814/6/Hatzikirou%20et%20al.pdf.txt
883792bb45e9c1ef68a02b8e5ef6b668
MD5
6
false
THUMBNAIL
Hatzikirou et al.pdf.jpg
Hatzikirou et al.pdf.jpg
Generated Thumbnail
image/jpeg
125431
https://hzi.openrepository.com/bitstream/10033/620814/7/Hatzikirou%20et%20al.pdf.jpg
33b69542123705f179ff42169ec4f0a1
MD5
7
false
10033/620814
oai:hzi.openrepository.com:10033/620814
2019-08-30 11:30:58.591
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6211962019-08-30T11:32:16Zcom_10033_620659col_10033_620660
He, Jin-Shu
98b5e001fd6fc8f42bd3117f061fa4ce
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Xiangying, Deng
cda7d63a85a4495e846bddd1b815e16a
500
Zuan, Lim Yok
a3bd4c072998e081d65c133546cef00f
500
Jones, Leigh Ann
10e9efd2e9abb90617bec26ca2e1c8be
500
Ramakrishna, Lakshmi
199edfa57d2d7ba0a005b17887def2b3
500
de Vries, Victor C
4358d4db9010ee0290bc65d56ddd0953
500
Dolpady, Jayashree
6c2f696458d30a382a1d4798c8b2aaf5
500
Aina, Hoi
062924693dcb4244b0190c14182724bc
500
Joseph, Sabrina
fbe269a431af34c7875cd7e014e51e8f
500
Narayanan, Sriram
ef9c122c679cde2d46c81408ff2491a3
500
Subramaniam, Sharrada
c4da96509ce3edf8680b1d43748b6c7e
500
Puthia, Manoj
d439cee10f452ab0844f528a1934fe95
500
Wong, Glenn
486443f72f5743eb8e3b9233fb3e2f03
500
Xiong, Huizhong
b02b79df3ed9affe17971992eda6958f
500
Poidinger, Michael
d6eda3dece9614ce8a760639d37c2158
500
Urban, Joseph F
3b26d2fa19a40a6e073fad6fc8a86387
500
Lafaille, Juan J
3a45712713c6d00a0f1d39d87eb5bf50
500
Curotto de Lafaille, Maria A
5d06dd808d0fc0fa2c834ba4f40c24a0
500
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7, 30625 Hannover, Germany.
2017-12-05T13:23:11Z
2017-12-05T13:23:11Z
2013-11-18
The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. 2013, 210 (12):2755-71 J. Exp. Med.
1540-9538
24218137
10.1084/jem.20131539
http://hdl.handle.net/10033/621196
The Journal of experimental medicine
The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE(+) cells in memory responses is particularly unclear. IgE(+) B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE(+) GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE(+) GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE(+) GC cells, whereas sequential switching gives rise to IgE(+) PCs. We propose a comprehensive model for the generation and memory of IgE responses.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Animals
Apoptosis
B-Lymphocytes
Cell Differentiation
Germinal Center
Green Fluorescent Proteins
Immunoglobulin Class Switching
Immunoglobulin E
Immunoglobulin G
Immunologic Memory
Mice
Mice, Inbred BALB C
Mice, Transgenic
Models, Immunological
Nippostrongylus
Plasma Cells
Receptors, Antigen, B-Cell
Signal Transduction
Strongylida Infections
The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response.
Article
2018-06-13T15:48:22Z
The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE(+) cells in memory responses is particularly unclear. IgE(+) B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE(+) GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE(+) GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE(+) GC cells, whereas sequential switching gives rise to IgE(+) PCs. We propose a comprehensive model for the generation and memory of IgE responses.
CONVERTED2_3541380
supplemental table S2.pdf
supplemental table S2.pdf
application/pdf
190579
https://hzi.openrepository.com/bitstream/10033/621196/13/supplemental%20table%20S2.pdf
1b651bf02e45ab2461ba9a8cc738de37
MD5
13
false
ORIGINAL
He et al.pdf
He et al.pdf
alowed publishers PDF
application/pdf
3921754
https://hzi.openrepository.com/bitstream/10033/621196/1/He%20et%20al.pdf
ec3cae44e913ab5917578784f8f56616
MD5
1
true
Supp.information.pdf
Supp.information.pdf
supplemental information
application/pdf
1509406
https://hzi.openrepository.com/bitstream/10033/621196/8/Supp.information.pdf
65054ed7c19870d58ba9fbbc8fa7152b
MD5
8
false
supplemental table S2.xls
supplemental table S2.xls
supplemental table S2
application/vnd.ms-excel
158720
https://hzi.openrepository.com/bitstream/10033/621196/9/supplemental%20table%20S2.xls
d35db58d70631bfa3122f238e8aa7ba2
MD5
9
false
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621196/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621196/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621196/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621196/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
He et al.pdf.txt
He et al.pdf.txt
Extracted Text
text/plain
86145
https://hzi.openrepository.com/bitstream/10033/621196/6/He%20et%20al.pdf.txt
19ffa9ebf3c687363c01ba472a413417
MD5
6
false
Supp.information.pdf.txt
Supp.information.pdf.txt
Extracted text
text/plain
3541
https://hzi.openrepository.com/bitstream/10033/621196/10/Supp.information.pdf.txt
362e8ef6882a1fb5520fcd1638f1c468
MD5
10
false
THUMBNAIL
He et al.pdf.jpg
He et al.pdf.jpg
Generated Thumbnail
image/jpeg
132314
https://hzi.openrepository.com/bitstream/10033/621196/7/He%20et%20al.pdf.jpg
80302b109f7c2a507afb2b9fbead6bc0
MD5
7
false
Supp.information.pdf.jpg
Supp.information.pdf.jpg
Generated Thumbnail
image/jpeg
59292
https://hzi.openrepository.com/bitstream/10033/621196/11/Supp.information.pdf.jpg
e068ca7e08ca2b309d923c5856faccb7
MD5
11
false
supplemental table S2.xls.jpg
supplemental table S2.xls.jpg
Generated Thumbnail
image/jpeg
126608
https://hzi.openrepository.com/bitstream/10033/621196/12/supplemental%20table%20S2.xls.jpg
c9ce6aa7ff078434e2ac58482ff4d24e
MD5
12
false
10033/621196
oai:hzi.openrepository.com:10033/621196
2019-08-30 11:32:16.916
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6212042019-08-30T11:26:42Zcom_10033_620659com_10033_620652com_10033_128109col_10033_621829col_10033_620672col_10033_620660
Zhao, Gang
37ec65924f58972f17d1469d470e37d8
500
Wirth, Dagmar
767830ff5044852eed4b5a554bbe9db0
500
Schmitz, Ingo
33252c7e3ac40c72ff226b0ae1187c4b
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106, Germany.
2017-12-13T09:08:17Z
2017-12-13T09:08:17Z
2017-11-08
A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance. 2017, 8 (1):1362 Nat Commun
2041-1723
29118381
10.1038/s41467-017-01627-9
http://hdl.handle.net/10033/621204
Nature communications
Physiological insulin secretion exhibits various temporal patterns, the dysregulation of which is involved in diabetes development. We analyzed the impact of first-phase and pulsatile insulin release on glucose and lipid control with various hepatic insulin signaling networks. The mathematical model suggests that atypical protein kinase C (aPKC) undergoes a bistable switch-on and switch-off, under the control of insulin receptor substrate 2 (IRS2). The activation of IRS1 and IRS2 is temporally separated due to the inhibition of IRS1 by aPKC. The model further shows that the timing of aPKC switch-off is delayed by reduced first-phase insulin and reduced amplitude of insulin pulses. Based on these findings, we propose a sequential model of postprandial hepatic control of glucose and lipid by insulin, according to which delayed aPKC switch-off contributes to selective hepatic insulin resistance, which is a long-standing paradox in the field.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.
Article
2018-05-23T10:16:34Z
Physiological insulin secretion exhibits various temporal patterns, the dysregulation of which is involved in diabetes development. We analyzed the impact of first-phase and pulsatile insulin release on glucose and lipid control with various hepatic insulin signaling networks. The mathematical model suggests that atypical protein kinase C (aPKC) undergoes a bistable switch-on and switch-off, under the control of insulin receptor substrate 2 (IRS2). The activation of IRS1 and IRS2 is temporally separated due to the inhibition of IRS1 by aPKC. The model further shows that the timing of aPKC switch-off is delayed by reduced first-phase insulin and reduced amplitude of insulin pulses. Based on these findings, we propose a sequential model of postprandial hepatic control of glucose and lipid by insulin, according to which delayed aPKC switch-off contributes to selective hepatic insulin resistance, which is a long-standing paradox in the field.
ORIGINAL
Zhao et al.pdf
Zhao et al.pdf
Open Access publication
application/pdf
1038987
https://hzi.openrepository.com/bitstream/10033/621204/1/Zhao%20et%20al.pdf
2bb85382b1224d3f635793b1a4ca4ee7
MD5
1
true
Supplementary information.pdf
Supplementary information.pdf
supplementary information
application/pdf
406994
https://hzi.openrepository.com/bitstream/10033/621204/2/Supplementary%20information.pdf
cd8ae8b486307be730a0930c098f2616
MD5
2
false
supplementary data 1.xls
supplementary data 1.xls
supplementary data
application/vnd.ms-excel
14848
https://hzi.openrepository.com/bitstream/10033/621204/3/supplementary%20data%201.xls
d4fa06b36d7c04689494def19b075fa6
MD5
3
false
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621204/4/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
4
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621204/5/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
5
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621204/6/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
6
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621204/7/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
7
false
TEXT
Zhao et al.pdf.txt
Zhao et al.pdf.txt
Extracted Text
text/plain
60430
https://hzi.openrepository.com/bitstream/10033/621204/8/Zhao%20et%20al.pdf.txt
40b4720fd269a9c1adfdf5b6a3debf60
MD5
8
false
Supplementary information.pdf.txt
Supplementary information.pdf.txt
Extracted Text
text/plain
21892
https://hzi.openrepository.com/bitstream/10033/621204/10/Supplementary%20information.pdf.txt
da38a714fc0611930206ef3de5baca0f
MD5
10
false
supplementary data 1.xls.txt
supplementary data 1.xls.txt
Extracted text
text/plain
5532
https://hzi.openrepository.com/bitstream/10033/621204/12/supplementary%20data%201.xls.txt
e1a4a7a284720d740591d952f2d7adc5
MD5
12
false
THUMBNAIL
supplementary data 1.xls.jpg
supplementary data 1.xls.jpg
Generated Thumbnail
image/jpeg
51703
https://hzi.openrepository.com/bitstream/10033/621204/13/supplementary%20data%201.xls.jpg
640969dd369728e4fdd89de7e64df430
MD5
13
false
Zhao et al.pdf.jpg
Zhao et al.pdf.jpg
Generated Thumbnail
image/jpeg
60747
https://hzi.openrepository.com/bitstream/10033/621204/15/Zhao%20et%20al.pdf.jpg
33a57f325aecbca162abd857e29a910e
MD5
15
false
Supplementary information.pdf.jpg
Supplementary information.pdf.jpg
Generated Thumbnail
image/jpeg
51699
https://hzi.openrepository.com/bitstream/10033/621204/16/Supplementary%20information.pdf.jpg
23b12c18bb504ce4b851bbea31ed182c
MD5
16
false
CONVERTED2_3534558
supplementary data 1.pdf
supplementary data 1.pdf
application/pdf
27861
https://hzi.openrepository.com/bitstream/10033/621204/14/supplementary%20data%201.pdf
099afbe35be8f687943b09c4aa6e4795
MD5
14
false
10033/621204
oai:hzi.openrepository.com:10033/621204
2019-08-30 11:26:42.727
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6212112019-08-30T11:37:23Zcom_10033_620659col_10033_620660
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
López Alfonso, Juan Carlos
9424f8eee94aa0a45a9effdea53f09ee
500
Leschner, Sara
de85addaac47ee7237929685a67f53a7
500
Weiss, Siegfried
2d17d733cc02ae4908b4c002ef13f553
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2017-12-19T14:47:16Z
2017-12-19T14:47:16Z
2017-04-01
Therapeutic Potential of Bacteria against Solid Tumors. 2017, 77 (7):1553-1563 Cancer Res.
1538-7445
28202530
10.1158/0008-5472.CAN-16-1621
http://hdl.handle.net/10033/621211
Cancer research
Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects. Cancer Res; 77(7); 1553-63. ©2017 AACR.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Animals
Bacterial Infections
Bacterial Load
Cell Line, Tumor
Disease Models, Animal
Humans
Mice
Mice, Inbred BALB C
Models, Theoretical
Neoplasms
Tumor Burden
Tumor Necrosis Factor-alpha
Therapeutic Potential of Bacteria against Solid Tumors.
Article
2018-02-15T00:00:00Z
Intentional bacterial infections can produce efficacious antitumor responses in mice, rats, dogs, and humans. However, low overall success rates and intense side effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the proinflammatory cytokine TNFα in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNFα enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pretreatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells postinjection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNFα administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects. Cancer Res; 77(7); 1553-63. ©2017 AACR.
ORIGINAL
Hatzikirou et al.pdf
Hatzikirou et al.pdf
original manuscript
application/pdf
1756489
https://hzi.openrepository.com/bitstream/10033/621211/1/Hatzikirou%20et%20al.pdf
5d2448170322e4eea8cb3fe530598e57
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621211/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621211/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621211/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621211/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Hatzikirou et al.pdf.txt
Hatzikirou et al.pdf.txt
Extracted Text
text/plain
61233
https://hzi.openrepository.com/bitstream/10033/621211/6/Hatzikirou%20et%20al.pdf.txt
7e415a9af617d22c82d614ffd1323686
MD5
6
false
THUMBNAIL
Hatzikirou et al.pdf.jpg
Hatzikirou et al.pdf.jpg
Generated Thumbnail
image/jpeg
96758
https://hzi.openrepository.com/bitstream/10033/621211/7/Hatzikirou%20et%20al.pdf.jpg
b8986143dfe686b5da7fca7d21a3b431
MD5
7
false
10033/621211
oai:hzi.openrepository.com:10033/621211
2019-08-30 11:37:23.915
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6212272019-08-30T11:37:23Zcom_10033_620659col_10033_620660
Alfonso, J C L
896385bb2f19a731862f77b3c56a717d
500
Talkenberger, K
637b47df4a10d9a7b920abde7b043cde
500
Seifert, M
dc55f5a9dcf74a8ad171d5d0a68383ce
500
Klink, B
f56a9e6bc4806ac50f93dd6a33fbda5b
500
Hawkins-Daarud, A
a37aafa2907bde2127f52f9f1991879b
500
Swanson, K R
a3dd736425d5f18a564d442a46147aed
500
Hatzikirou, H
32b9e34beb5f7b9e23a066cf51d460df
500
Deutsch, A
e47a1b66028665186c7b8948ae70fa4b
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-01-09T11:59:13Z
2018-01-09T11:59:13Z
2017-11
The biology and mathematical modelling of glioma invasion: a review. 2017, 14 (136) J R Soc Interface
1742-5662
29118112
10.1098/rsif.2017.0490
http://hdl.handle.net/10033/621227
Journal of the Royal Society, Interface
5721156
Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low- to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.
en
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721156/
http://creativecommons.org/licenses/by-nc-sa/4.0/
The biology and mathematical modelling of glioma invasion: a review.
Article
2018-06-13T04:12:07Z
Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low- to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.
ORIGINAL
Alfonso et al.pdf
Alfonso et al.pdf
free text from PubMed's free repository PMC
application/pdf
1394862
https://hzi.openrepository.com/bitstream/10033/621227/1/Alfonso%20et%20al.pdf
a7df11c64dfd7e75fbc93a401665001a
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621227/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621227/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621227/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621227/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Alfonso et al.pdf.txt
Alfonso et al.pdf.txt
Extracted Text
text/plain
129457
https://hzi.openrepository.com/bitstream/10033/621227/6/Alfonso%20et%20al.pdf.txt
8430410391462c2e7506ff7f49cb70a3
MD5
6
false
THUMBNAIL
Alfonso et al.pdf.jpg
Alfonso et al.pdf.jpg
Generated Thumbnail
image/jpeg
128226
https://hzi.openrepository.com/bitstream/10033/621227/7/Alfonso%20et%20al.pdf.jpg
c3404f9b8db8aa941a818828c5027850
MD5
7
false
10033/621227
oai:hzi.openrepository.com:10033/621227
2019-08-30 11:37:23.94
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6212462019-08-30T11:34:48Zcom_10033_620659col_10033_620660
Nava-Sedeño, J M
cbd1bef3eed4c586520649d19e3355dc
500
Hatzikirou, H
32b9e34beb5f7b9e23a066cf51d460df
500
Klages, R
a54c2869adf8575232d9650e4ac155d6
500
Deutsch, A
e47a1b66028665186c7b8948ae70fa4b
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-01-22T08:57:45Z
2018-01-22T08:57:45Z
2017-12-05
Cellular automaton models for time-correlated random walks: derivation and analysis. 2017, 7 (1):16952 Sci Rep
2045-2322
29209065
10.1038/s41598-017-17317-x
http://hdl.handle.net/10033/621246
Scientific reports
Many diffusion processes in nature and society were found to be anomalous, in the sense of being fundamentally different from conventional Brownian motion. An important example is the migration of biological cells, which exhibits non-trivial temporal decay of velocity autocorrelation functions. This means that the corresponding dynamics is characterized by memory effects that slowly decay in time. Motivated by this we construct non-Markovian lattice-gas cellular automata models for moving agents with memory. For this purpose the reorientation probabilities are derived from velocity autocorrelation functions that are given a priori; in that respect our approach is "data-driven". Particular examples we consider are velocity correlations that decay exponentially or as power laws, where the latter functions generate anomalous diffusion. The computational efficiency of cellular automata combined with our analytical results paves the way to explore the relevance of memory and anomalous diffusion for the dynamics of interacting cell populations, like confluent cell monolayers and cell clustering.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Cellular automaton models for time-correlated random walks: derivation and analysis.
Article
2018-06-13T05:38:23Z
Many diffusion processes in nature and society were found to be anomalous, in the sense of being fundamentally different from conventional Brownian motion. An important example is the migration of biological cells, which exhibits non-trivial temporal decay of velocity autocorrelation functions. This means that the corresponding dynamics is characterized by memory effects that slowly decay in time. Motivated by this we construct non-Markovian lattice-gas cellular automata models for moving agents with memory. For this purpose the reorientation probabilities are derived from velocity autocorrelation functions that are given a priori; in that respect our approach is "data-driven". Particular examples we consider are velocity correlations that decay exponentially or as power laws, where the latter functions generate anomalous diffusion. The computational efficiency of cellular automata combined with our analytical results paves the way to explore the relevance of memory and anomalous diffusion for the dynamics of interacting cell populations, like confluent cell monolayers and cell clustering.
ORIGINAL
Nava-Sedeño et al.pdf
Nava-Sedeño et al.pdf
Open Access publication
application/pdf
3052600
https://hzi.openrepository.com/bitstream/10033/621246/1/Nava-Sede%c3%b1o%20et%20al.pdf
367301e2794259d24d71af5a2a00ffa7
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621246/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621246/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621246/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621246/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Nava-Sedeño et al.pdf.txt
Nava-Sedeño et al.pdf.txt
Extracted Text
text/plain
55093
https://hzi.openrepository.com/bitstream/10033/621246/6/Nava-Sede%c3%b1o%20et%20al.pdf.txt
731718d4ca19506191778846717b430c
MD5
6
false
THUMBNAIL
Nava-Sedeño et al.pdf.jpg
Nava-Sedeño et al.pdf.jpg
Generated Thumbnail
image/jpeg
113371
https://hzi.openrepository.com/bitstream/10033/621246/7/Nava-Sede%c3%b1o%20et%20al.pdf.jpg
e6fd952b463f3c57b9527d1b9b46f3f5
MD5
7
false
10033/621246
oai:hzi.openrepository.com:10033/621246
2019-08-30 11:34:48.342
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6212492019-08-30T11:32:17Zcom_10033_620659col_10033_620660
Volk, Valery
471270676314f896c59426533c0b8380
500
Reppas, Andreas I
77a81b41c35b44608fa168d03da0c68d
500
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Spineli, Loukia M
767e9dbac76e3b3bd693a701599be13d
500
Sundarasetty, Bala Sai
721623a4867a6397f6982ffed1cc0df3
500
Theobald, Sebastian J
b20691f6a8eaced112a6952abc279f6f
500
Schneider, Andreas
e0f0eceff50ffc02b2f2f318141b786f
500
Gerasch, Laura
3bbcd0152f10042213c296f4af88fb6e
500
Deves Roth, Candida
eb36bc247ff0a23085524902fb77f736
500
Klöss, Stephan
8c36551dca3e763bb40e648727864be3
500
Koehl, Ulrike
bb5bc85cbd5ba862630c1b48cd37e222
500
von Kaisenberg, Constantin
2bd0ee839910049aaf2222bb2103acdf
500
Figueiredo, Constanca
9a7a1b9898006185f224072e816a4c9b
500
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Stripecke, Renata
2a542d77371b05057a72e0d5889405a2
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38124 Braunschweig, Germany.
2018-01-23T14:33:35Z
2018-01-23T14:33:35Z
2017
Multidimensional Analysis Integrating Human T-Cell Signatures in Lymphatic Tissues with Sex of Humanized Mice for Prediction of Responses after Dendritic Cell Immunization. 2017, 8:1709 Front Immunol
1664-3224
29276513
10.3389/fimmu.2017.01709
http://hdl.handle.net/10033/621249
Frontiers in immunology
Mice transplanted with human cord blood-derived hematopoietic stem cells (HSCs) became a powerful experimental tool for studying the heterogeneity of human immune reconstitution and immune responses in vivo. Yet, analyses of human T cell maturation in humanized models have been hampered by an overall low immune reactivity and lack of methods to define predictive markers of responsiveness. Long-lived human lentiviral induced dendritic cells expressing the cytomegalovirus pp65 protein (iDCpp65) promoted the development of pp65-specific human CD8+ T cell responses in NOD.Cg-Rag1 tm1Mom -Il2rγ tm1Wj humanized mice through the presentation of immune-dominant antigenic epitopes (signal 1), expression of co-stimulatory molecules (signal 2), and inflammatory cytokines (signal 3). We exploited this validated system to evaluate the effects of mouse sex in the dynamics of T cell homing and maturation status in thymus, blood, bone marrow, spleen, and lymph nodes. Statistical analyses of cell relative frequencies and absolute numbers demonstrated higher CD8+ memory T cell reactivity in spleen and lymph nodes of immunized female mice. In order to understand to which extent the multidimensional relation between organ-specific markers predicted the immunization status, the immunophenotypic profiles of individual mice were used to train an artificial neural network designed to discriminate immunized and non-immunized mice. The highest accuracy of immune reactivity prediction could be obtained from lymph node markers of female mice (77.3%). Principal component analyses further identified clusters of markers best suited to describe the heterogeneity of immunization responses in vivo. A correlation analysis of these markers reflected a tissue-specific impact of immunization. This allowed for an organ-resolved characterization of the immunization status of individual mice based on the identified set of markers. This new modality of multidimensional analyses can be used as a framework for defining minimal but predictive signatures of human immune responses in mice and suggests critical markers to characterize responses to immunization after HSC transplantation.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Multidimensional Analysis Integrating Human T-Cell Signatures in Lymphatic Tissues with Sex of Humanized Mice for Prediction of Responses after Dendritic Cell Immunization.
Article
2018-06-13T05:39:47Z
Mice transplanted with human cord blood-derived hematopoietic stem cells (HSCs) became a powerful experimental tool for studying the heterogeneity of human immune reconstitution and immune responses in vivo. Yet, analyses of human T cell maturation in humanized models have been hampered by an overall low immune reactivity and lack of methods to define predictive markers of responsiveness. Long-lived human lentiviral induced dendritic cells expressing the cytomegalovirus pp65 protein (iDCpp65) promoted the development of pp65-specific human CD8+ T cell responses in NOD.Cg-Rag1 tm1Mom -Il2rγ tm1Wj humanized mice through the presentation of immune-dominant antigenic epitopes (signal 1), expression of co-stimulatory molecules (signal 2), and inflammatory cytokines (signal 3). We exploited this validated system to evaluate the effects of mouse sex in the dynamics of T cell homing and maturation status in thymus, blood, bone marrow, spleen, and lymph nodes. Statistical analyses of cell relative frequencies and absolute numbers demonstrated higher CD8+ memory T cell reactivity in spleen and lymph nodes of immunized female mice. In order to understand to which extent the multidimensional relation between organ-specific markers predicted the immunization status, the immunophenotypic profiles of individual mice were used to train an artificial neural network designed to discriminate immunized and non-immunized mice. The highest accuracy of immune reactivity prediction could be obtained from lymph node markers of female mice (77.3%). Principal component analyses further identified clusters of markers best suited to describe the heterogeneity of immunization responses in vivo. A correlation analysis of these markers reflected a tissue-specific impact of immunization. This allowed for an organ-resolved characterization of the immunization status of individual mice based on the identified set of markers. This new modality of multidimensional analyses can be used as a framework for defining minimal but predictive signatures of human immune responses in mice and suggests critical markers to characterize responses to immunization after HSC transplantation.
ORIGINAL
Volk et al.pdf
Volk et al.pdf
Open Access publication
application/pdf
6739610
https://hzi.openrepository.com/bitstream/10033/621249/1/Volk%20et%20al.pdf
785e13be86790738e424545af9074ae8
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621249/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621249/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621249/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621249/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Volk et al.pdf.txt
Volk et al.pdf.txt
Extracted Text
text/plain
86191
https://hzi.openrepository.com/bitstream/10033/621249/6/Volk%20et%20al.pdf.txt
f546539b44995a5aa911879fdd119e3d
MD5
6
false
THUMBNAIL
Volk et al.pdf.jpg
Volk et al.pdf.jpg
Generated Thumbnail
image/jpeg
136031
https://hzi.openrepository.com/bitstream/10033/621249/7/Volk%20et%20al.pdf.jpg
977b7e3fff9874c7d9ad0a78db870bd8
MD5
7
false
10033/621249
oai:hzi.openrepository.com:10033/621249
2019-08-30 11:32:17.029
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6213012019-08-30T11:25:43Zcom_10033_620659com_10033_620636col_10033_620660col_10033_620637
Ghanbari, Azadeh
d19ab7ea25761150218f0115a02a9712
500
Dehghany, Jaber
763519d6de38b945a2f96901ec0a5047
500
Schwebs, Timo
48df9421f9a56e4ed2fd222f5ead381c
500
Müsken, Mathias
1204ff304c7364acca1cb3303dffeb45
500
Häussler, Susanne
d2527fb005be9775f94b5de7f3de1fbf
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-03-02T14:24:49Z
2018-03-02T14:24:49Z
2016-09-09
Inoculation density and nutrient level determine the formation of mushroom-shaped structures in Pseudomonas aeruginosa biofilms. 2016, 6:32097 Sci Rep
2045-2322
27611778
10.1038/srep32097
http://hdl.handle.net/10033/621301
Scientific reports
Pseudomonas aeruginosa often colonises immunocompromised patients and the lungs of cystic fibrosis patients. It exhibits resistance to many antibiotics by forming biofilms, which makes it hard to eliminate. P. aeruginosa biofilms form mushroom-shaped structures under certain circumstances. Bacterial motility and the environment affect the eventual mushroom morphology. This study provides an agent-based model for the bacterial dynamics and interactions influencing bacterial biofilm shape. Cell motility in the model relies on recently published experimental data. Our simulations show colony formation by immotile cells. Motile cells escape from a single colony by nutrient chemotaxis and hence no mushroom shape develops. A high number density of non-motile colonies leads to migration of motile cells onto the top of the colonies and formation of mushroom-shaped structures. This model proposes that the formation of mushroom-shaped structures can be predicted by parameters at the time of bacteria inoculation. Depending on nutrient levels and the initial number density of stalks, mushroom-shaped structures only form in a restricted regime. This opens the possibility of early manipulation of spatial pattern formation in bacterial colonies, using environmental factors.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Inoculation density and nutrient level determine the formation of mushroom-shaped structures in Pseudomonas aeruginosa biofilms.
Article
2018-06-13T01:08:21Z
Pseudomonas aeruginosa often colonises immunocompromised patients and the lungs of cystic fibrosis patients. It exhibits resistance to many antibiotics by forming biofilms, which makes it hard to eliminate. P. aeruginosa biofilms form mushroom-shaped structures under certain circumstances. Bacterial motility and the environment affect the eventual mushroom morphology. This study provides an agent-based model for the bacterial dynamics and interactions influencing bacterial biofilm shape. Cell motility in the model relies on recently published experimental data. Our simulations show colony formation by immotile cells. Motile cells escape from a single colony by nutrient chemotaxis and hence no mushroom shape develops. A high number density of non-motile colonies leads to migration of motile cells onto the top of the colonies and formation of mushroom-shaped structures. This model proposes that the formation of mushroom-shaped structures can be predicted by parameters at the time of bacteria inoculation. Depending on nutrient levels and the initial number density of stalks, mushroom-shaped structures only form in a restricted regime. This opens the possibility of early manipulation of spatial pattern formation in bacterial colonies, using environmental factors.
ORIGINAL
Chanbari et al.pdf
Chanbari et al.pdf
Open Access publication
application/pdf
2428299
https://hzi.openrepository.com/bitstream/10033/621301/1/Chanbari%20et%20al.pdf
224f4f27d98cb915405586cac9a2a2d9
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621301/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621301/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621301/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621301/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Chanbari et al.pdf.txt
Chanbari et al.pdf.txt
Extracted Text
text/plain
59311
https://hzi.openrepository.com/bitstream/10033/621301/6/Chanbari%20et%20al.pdf.txt
677e8e68d584d6152904594e4dd06f39
MD5
6
false
THUMBNAIL
Chanbari et al.pdf.jpg
Chanbari et al.pdf.jpg
Generated Thumbnail
image/jpeg
112183
https://hzi.openrepository.com/bitstream/10033/621301/7/Chanbari%20et%20al.pdf.jpg
3cb5dfcf91d8035fd55b43d31d90ad86
MD5
7
false
10033/621301
oai:hzi.openrepository.com:10033/621301
2019-08-30 11:25:43.541
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6213222019-08-30T11:32:41Zcom_10033_620659col_10033_620660
Binder, Sebastian C
5f59b1f232c7fd9dd584163b14e1b927
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-03-14T10:27:20Z
2018-03-14T10:27:20Z
2016
Implications of Intravital Imaging of Murine Germinal Centers on the Control of B Cell Selection and Division. 2016, 7:593 Front Immunol
1664-3224
28066409
10.3389/fimmu.2016.00593
http://hdl.handle.net/10033/621322
Frontiers in immunology
Intravital imaging of antibody optimization in germinal center (GC) reactions has set a new dimension in the understanding of the humoral immune response during the last decade. The inclusion of spatio-temporal cellular dynamics in the research on GCs required analysis using the agent-based mathematical models. In this study, we integrate the available intravital imaging data from various research groups and incorporate these into a quantitative mathematical model of GC reactions and antibody affinity maturation. Interestingly, the integration of data concerning the spatial organization of GCs and B cell motility allows to draw conclusions on the strength of the selection pressure and the control of B cell division by T follicular helper cells.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Implications of Intravital Imaging of Murine Germinal Centers on the Control of B Cell Selection and Division.
Article
2018-06-12T18:08:40Z
Intravital imaging of antibody optimization in germinal center (GC) reactions has set a new dimension in the understanding of the humoral immune response during the last decade. The inclusion of spatio-temporal cellular dynamics in the research on GCs required analysis using the agent-based mathematical models. In this study, we integrate the available intravital imaging data from various research groups and incorporate these into a quantitative mathematical model of GC reactions and antibody affinity maturation. Interestingly, the integration of data concerning the spatial organization of GCs and B cell motility allows to draw conclusions on the strength of the selection pressure and the control of B cell division by T follicular helper cells.
ORIGINAL
Binder and Meyer-Hermann.pdf
Binder and Meyer-Hermann.pdf
Open Access publication
application/pdf
3959734
https://hzi.openrepository.com/bitstream/10033/621322/1/Binder%20and%20Meyer-Hermann.pdf
e5e844c18932484c6ae815b493db4efa
MD5
1
true
CC-LICENSE
license_url
license_url
text/plain
49
https://hzi.openrepository.com/bitstream/10033/621322/2/license_url
924993ce0b3ba389f79f32a1b2735415
MD5
2
false
license_text
license_text
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621322/3/license_text
d41d8cd98f00b204e9800998ecf8427e
MD5
3
false
license_rdf
license_rdf
application/octet-stream
0
https://hzi.openrepository.com/bitstream/10033/621322/4/license_rdf
d41d8cd98f00b204e9800998ecf8427e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621322/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
TEXT
Binder and Meyer-Hermann.pdf.txt
Binder and Meyer-Hermann.pdf.txt
Extracted Text
text/plain
49216
https://hzi.openrepository.com/bitstream/10033/621322/6/Binder%20and%20Meyer-Hermann.pdf.txt
3d6f704c5a6c9cc1b97e657af96f4a96
MD5
6
false
THUMBNAIL
Binder and Meyer-Hermann.pdf.jpg
Binder and Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
120501
https://hzi.openrepository.com/bitstream/10033/621322/7/Binder%20and%20Meyer-Hermann.pdf.jpg
799e7e43bd511ed40f05d740662839e0
MD5
7
false
10033/621322
oai:hzi.openrepository.com:10033/621322
2019-08-30 11:32:41.202
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6214172020-07-09T08:39:43Zcom_10033_620659col_10033_620660
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-06-29T09:24:58Z
2018-06-29T09:24:58Z
2191-0243
10.1515/jmbm-2018-0001
http://hdl.handle.net/10033/621417
http://www.degruyter.com/view/j/jmbm.ahead-of-print/jmbm-2018-0001/jmbm-2018-0001.xml
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Statistical mechanics of cell decision-making: the cell migration force distribution
Article
0
0
Journal of the Mechanical Behavior of Materials
2018-06-29T09:31:26Z
ORIGINAL
Hatzikirou.pdf
Hatzikirou.pdf
Open Access article
application/pdf
785888
https://repository.helmholtz-hzi.de/bitstream/10033/621417/6/Hatzikirou.pdf
7456beb396c4a7dc8219b3d8ab9de3d5
MD5
6
true
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1037
https://repository.helmholtz-hzi.de/bitstream/10033/621417/2/license_rdf
80294ba9ff4c5b4f07812ee200fbc42f
MD5
2
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/621417/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
TEXT
Hatzikirou.pdf.txt
Hatzikirou.pdf.txt
Extracted text
text/plain
19943
https://repository.helmholtz-hzi.de/bitstream/10033/621417/4/Hatzikirou.pdf.txt
6253f39b56ba8adcc2fed0825f04bcf9
MD5
4
false
THUMBNAIL
Hatzikirou.pdf.jpg
Hatzikirou.pdf.jpg
Generated Thumbnail
image/jpeg
100830
https://repository.helmholtz-hzi.de/bitstream/10033/621417/5/Hatzikirou.pdf.jpg
1bef2d3483aa09eb86b4f81b8a4c33f4
MD5
5
false
10033/621417
oai:repository.helmholtz-hzi.de:10033/621417
2020-07-09 08:39:43.804
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6214552019-08-30T11:29:14Zcom_10033_620659col_10033_620660
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-08-27T14:21:30Z
2018-08-27T14:21:30Z
2018-08-06
2045-2322
30082874
10.1038/s41598-018-29967-6
http://hdl.handle.net/10033/621455
Rejuvenation of stem cell activity might increase life expectancy by prolonging functionality of organs. Higher stem cell replication rates also bear the risk of cancer. The extent of this risk is not known. While it is difficult to evaluate this cancer risk in experiments, it can be estimated using a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model recapitulates the observation that treatments targeting stem cell replication can induce a substantial delay of organ failure. The model predicts that the cancer risk is minor under particular conditions. It depends on the assumed implications for cell damage repair during treatment. The benefit of rejuvenation therapy and its impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of systemic treatments. In recent years, the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. In this context, the model predicts that the treatment schedule is critical for success and that schedules successful in animal experiments are not transferable to humans. Guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of stem cell rejuvenation treatment protocols and the identification of critical parameters for cancer risk.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Estimation of the cancer risk induced by therapies targeting stem cell replication and treatment recommendations.
Article
Scientific reports
2018-08-27T14:21:30Z
THUMBNAIL
Meyer-Hermann.pdf.jpg
Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
110378
https://hzi.openrepository.com/bitstream/10033/621455/5/Meyer-Hermann.pdf.jpg
aaba5e0d46cb1050ae3bdd25cc00a4ab
MD5
5
false
TEXT
Meyer-Hermann.pdf.txt
Meyer-Hermann.pdf.txt
Extracted text
text/plain
58795
https://hzi.openrepository.com/bitstream/10033/621455/4/Meyer-Hermann.pdf.txt
96cd577406a4fade6bd00d2662352c4f
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621455/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1037
https://hzi.openrepository.com/bitstream/10033/621455/2/license_rdf
80294ba9ff4c5b4f07812ee200fbc42f
MD5
2
false
ORIGINAL
Meyer-Hermann.pdf
Meyer-Hermann.pdf
Open Access publication
application/pdf
3647994
https://hzi.openrepository.com/bitstream/10033/621455/1/Meyer-Hermann.pdf
6b633aaeb39936565054d86e7005d556
MD5
1
true
10033/621455
oai:hzi.openrepository.com:10033/621455
2019-08-30 11:29:14.644
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6215112019-08-30T11:29:45Zcom_10033_620659col_10033_620660
Montaseri, Ghazal
0188311a96861e58b03f0dde1e12040f
500
Boianelli, Alessandro
8d9960dd5670271aff55581d1daa4dc2
500
Hernandez-Vargas, Esteban A
f5f76475c898e2d172a51445be77c1ec
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-10-10T08:47:31Z
2018-10-10T08:47:31Z
2018-07-19
1873-1732
30031022
10.1016/j.pbiomolbio.2018.07.007
http://hdl.handle.net/10033/621511
Influenza A virus (IAV) is a latent global threat to human health. In view of the risk of pandemics, prophylactic and curative treatments are essential. Oseltamivir is a neuraminidase inhibitor efficiently supporting recovery from influenza infections. Current common clinical practice is a constant drug dose (75 or 150 mg) administered at regular time intervals twice a day. We aim to use quantitative systems pharmacology to propose an efficient adaptive drug scheduling. We combined the mathematical model for IAV infections validated by murine data, which captures the viral dynamics and the dynamics of the immune host response, with a pharmacokinetic (PK)/pharmacodynamic (PD) model of oseltamivir. Next, we applied an adaptive impulsive feedback control method to systematically calculate the adaptive dose of oseltamivir in dependence on the viral load and the number of immune effectors at the time of drug administration. Our in silico results revealed that the treatment with adaptive control-based drug scheduling is able to either increase the drug virological efficacy or reduce the drug dose while keeping the same virological efficacy. Thus, adaptive adjustment of the drug dose would reduce not only the potential side effects but also the amount of stored oseltamivir required for the prevention of outbreaks.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Impulsive control
fbeaa1a3-fefc-4123-8cc8-9e86f07d8075
Influenza viral infections
4fdff168-0a6e-4a0f-9705-0e504c0c1934
Oseltamivir
1c3d42c9-07b1-496c-b70f-46247c8169aa
PK/PD modeling
b1f1059c-0f6b-4dcb-a4f5-d13b57f738f0
PK/PD-based adaptive tailoring of oseltamivir doses to treat within-host influenza viral infections.
Article
Progress in biophysics and molecular biology
THUMBNAIL
Montaseri et al.jpg
Montaseri et al.jpg
Generated Thumbnail
image/jpeg
60006
https://hzi.openrepository.com/bitstream/10033/621511/5/Montaseri%20et%20al.jpg
259955185f0f95c6bff3cc5851caf36a
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
56267
https://hzi.openrepository.com/bitstream/10033/621511/6/elsevier-thumbnail.png
f821b8fa7d77b3b63a87291fbd17d255
MD5
6
false
TEXT
Montaseri et al.txt
Montaseri et al.txt
Extracted text
text/plain
93338
https://hzi.openrepository.com/bitstream/10033/621511/4/Montaseri%20et%20al.txt
50153e9b4335b59192feb7675b65fb48
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621511/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1037
https://hzi.openrepository.com/bitstream/10033/621511/2/license_rdf
80294ba9ff4c5b4f07812ee200fbc42f
MD5
2
false
ORIGINAL
Montaseri et al
Montaseri et al
Original manuscript with Appendix A and supplementary material
application/pdf
3293777
https://hzi.openrepository.com/bitstream/10033/621511/1/Montaseri%20et%20al
1486343d6a182bbf9fa4d9a216c39838
MD5
1
true
10033/621511
oai:hzi.openrepository.com:10033/621511
2019-08-30 11:29:45.774
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6215332019-08-30T11:29:40Zcom_10033_128109com_10033_620659col_10033_128110col_10033_620660
Prajeeth, Chittappen K
1faceeca5ee6c0e68b98d6d6f50aa930
500
Dittrich-Breiholz, Oliver
24da1211f0e6be78ed84b7ac478d9336
500
Talbot, Steven R
ef84781366d70f083c6f8fbc307a8c6e
500
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Huehn, Jochen
81855dd40035a02edad8ee83ce210282
500
Stangel, Martin
c34c7db9fb99df1894fa38347613609e
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2018-11-02T11:50:11Z
2018-11-02T11:50:11Z
2018-01-01
1662-5102
30364000
10.3389/fncel.2018.00352
http://hdl.handle.net/10033/621533
Autoreactive T cells that infiltrate into the central nervous system (CNS) are believed to have a significant role in mediating the pathology of neuroinflammatory diseases like multiple sclerosis. Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of neuroinflammatory processes. Our previous work demonstrated that effectors secreted by Th1 and Th17 cells have different capacities to influence the phenotype and function of glial cells. We have shown that Th1-derived effectors altered the phenotype and function of both microglia and astrocytes whereas Th17-derived effectors induced direct effects only on astrocytes but not on microglia. Here we investigated if effector molecules associated with IFN-γ producing Th1 cells induced different gene expression profiles in microglia and astrocytes. We performed a microarray analysis of RNA isolated from microglia and astrocytes treated with medium and Th-derived culture supernatants and compared the gene expression data. By using the criteria of 2-fold change and a false discovery rate of 0.01 (corrected
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Th1 cells
898e6297-2bed-4024-849c-11f8fff016a7
astrocytes
d7757c77-fe13-462c-8951-0fc33a04e571
500
cytokines
e3332e21-33e0-404c-8c27-afe7eb3e983f
500
interferon-γ
bfe39deb-bddd-41fd-bdbc-9e98c48672a7
microglia
9de42de5-aa02-4cd1-bd46-616e8e24f118
IFN-γ Producing Th1 Cells Induce Different Transcriptional Profiles in Microglia and Astrocytes.
Article
Frontiers in cellular neuroscience
2018-11-02T11:50:12Z
THUMBNAIL
Prajeeth et al.pdf.jpg
Prajeeth et al.pdf.jpg
Generated Thumbnail
image/jpeg
122543
https://hzi.openrepository.com/bitstream/10033/621533/5/Prajeeth%20et%20al.pdf.jpg
2eca34709b11bfd9927b555730e737d7
MD5
5
false
TEXT
Prajeeth et al.pdf.txt
Prajeeth et al.pdf.txt
Extracted text
text/plain
69284
https://hzi.openrepository.com/bitstream/10033/621533/4/Prajeeth%20et%20al.pdf.txt
e826a4aec2cdd4a120d0716f960596a0
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621533/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1037
https://hzi.openrepository.com/bitstream/10033/621533/2/license_rdf
80294ba9ff4c5b4f07812ee200fbc42f
MD5
2
false
ORIGINAL
Prajeeth et al.pdf
Prajeeth et al.pdf
Open Access publication
application/pdf
3050913
https://hzi.openrepository.com/bitstream/10033/621533/1/Prajeeth%20et%20al.pdf
7e0541c9c7fd92d5c8e1fa46a7511bf0
MD5
1
true
10033/621533
oai:hzi.openrepository.com:10033/621533
2019-08-30 11:29:40.87
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6215342019-08-30T11:29:40Zcom_10033_620659col_10033_620660
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Binder, Sebastian C
5f59b1f232c7fd9dd584163b14e1b927
500
Mesin, Luka
1c119fe8cd293f8150f01ecb915d84ff
500
Victora, Gabriel D
f5d6a01775ef0b0c513db3746e04ee8d
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2018-11-02T12:06:40Z
2018-11-02T12:06:40Z
2018-01-01
1664-3224
30319600
10.3389/fimmu.2018.02020
http://hdl.handle.net/10033/621534
Clonal evolution of B cells in germinal centers (GCs) is central to affinity maturation of antibodies in response to pathogens. Permanent or tamoxifen-induced multi-color recombination of B cells based on the brainbow allele allows monitoring the degree of color dominance in the course of the GC reaction. Here, we use computer simulations of GC reactions in order to replicate the evolution of color dominance
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
brainbow
1918cb19-3b0a-46c0-8bf6-511e38c41125
clonal selection
d2dbc3be-0f5c-46c4-b2b1-93c7368fac50
computer simulation
d0ea3e6d-7f3a-43d4-94b2-2fcc6b621ba5
germinal center
b707c64c-c388-429f-80aa-2107d1e3813d
mathematical modeling
bf7212e5-a076-4383-9cf8-e44e81ddba83
multiphoton imaging
645b69b7-6e9e-43ff-8e64-87d0c1aee531
sequencing
df0d00b0-0be0-4d16-81e7-be2083b0d814
Computer Simulation of Multi-Color Brainbow Staining and Clonal Evolution of B Cells in Germinal Centers.
Article
Frontiers in immunology
2018-11-02T12:06:41Z
THUMBNAIL
Meyer-Hermann et al.pdf.jpg
Meyer-Hermann et al.pdf.jpg
Generated Thumbnail
image/jpeg
118148
https://hzi.openrepository.com/bitstream/10033/621534/5/Meyer-Hermann%20et%20al.pdf.jpg
301208234c3d6c0b180747779ab9b05d
MD5
5
false
TEXT
Meyer-Hermann et al.pdf.txt
Meyer-Hermann et al.pdf.txt
Extracted text
text/plain
57276
https://hzi.openrepository.com/bitstream/10033/621534/4/Meyer-Hermann%20et%20al.pdf.txt
5938d1372a4dd76baa86feafab10c3de
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621534/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1037
https://hzi.openrepository.com/bitstream/10033/621534/2/license_rdf
80294ba9ff4c5b4f07812ee200fbc42f
MD5
2
false
ORIGINAL
Meyer-Hermann et al.pdf
Meyer-Hermann et al.pdf
application/pdf
11148744
https://hzi.openrepository.com/bitstream/10033/621534/1/Meyer-Hermann%20et%20al.pdf
6ad5523c1a36724b73415dfe8ce8f756
MD5
1
true
10033/621534
oai:hzi.openrepository.com:10033/621534
2019-08-30 11:29:40.906
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6216482019-08-30T11:33:54Zcom_10033_620659com_10033_620652col_10033_620666col_10033_620660
Theobald, Sebastian J
b20691f6a8eaced112a6952abc279f6f
500
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Volk, Valery
471270676314f896c59426533c0b8380
500
Olbrich, Henning
6419f9e0e6535dff36a34f3097094543
500
Danisch, Simon
e414529cf27089a2211c9eadfe2cff3e
500
Gerasch, Laura
3bbcd0152f10042213c296f4af88fb6e
500
Schneider, Andreas
e0f0eceff50ffc02b2f2f318141b786f
500
Sinzger, Christian
d0bef7292d448279b215fddcc8e8653f
500
Schaudien, Dirk
2037c9ad0461e336af1aebf0799c80e2
500
Lienenklaus, Stefan
ddc50d051b6287e1137ccffd8f854cbb
600
http://orcid.org/0000-0003-4790-3445
Riese, Peggy
8c4f5faa7786444779b9cc589e124eb2
600
http://orcid.org/0000-0001-6796-6780
Guzman, Carlos A
1dc6fd50b3a3354f74ef8672c521d5c7
500
Figueiredo, Constanca
9a7a1b9898006185f224072e816a4c9b
500
von Kaisenberg, Constantin
2bd0ee839910049aaf2222bb2103acdf
500
Spineli, Loukia M
767e9dbac76e3b3bd693a701599be13d
500
Glaesener, Stephanie
b02361fbeb38287a1abfd7f66eae87f5
500
Meyer-Bahlburg, Almut
f92a77e79527e2d9df1c9bedb0c2ff77
500
Ganser, Arnold
8b171c8e333b6e9d41192eb6431063d8
500
Schmitt, Michael
f86d1468020f102d9cfdbec92ee23a1d
500
Mach, Michael
f1a94e23d197d07777b6f2ae76abfadd
500
Messerle, Martin
f32ed852de2e0307d35955c90176a6c1
500
Stripecke, Renata
2a542d77371b05057a72e0d5889405a2
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2019-01-15T13:45:26Z
2019-01-15T13:45:26Z
2018-01-01
- Front Immunol. 2018 Nov 22;9:2734. doi: 10.3389/fimmu.2018.02734. eCollection 2018.
1664-3224
30524448
10.3389/fimmu.2018.02734
http://hdl.handle.net/10033/621648
uman cytomegalovirus (HCMV) latency is typically harmless but reactivation can be largely detrimental to immune compromised hosts. We modeled latency and reactivation using a traceable HCMV laboratory strain expressing the Gaussia luciferase reporter gene (HCMV/GLuc) in order to interrogate the viral modulatory effects on the human adaptive immunity. Humanized mice with long-term (more than 17 weeks) steady human T and B cell immune reconstitutions were infected with HCMV/GLuc and 7 weeks later were further treated with granulocyte-colony stimulating factor (G-CSF) to induce viral reactivations. Whole body bio-luminescence imaging analyses clearly differentiated mice with latent viral infections vs. reactivations. Foci of vigorous viral reactivations were detectable in liver, lymph nodes and salivary glands. The number of viral genome copies in various tissues increased upon reactivations and were detectable in sorted human CD14+, CD169+, and CD34+ cells. Compared with non-infected controls, mice after infections and reactivations showed higher thymopoiesis, systemic expansion of Th, CTL, Treg, and Tfh cells and functional antiviral T cell responses. Latent infections promoted vast development of memory CD4+ T cells while reactivations triggered a shift toward effector T cells expressing PD-1. Further, reactivations prompted a marked development of B cells, maturation of IgG+ plasma cells, and HCMV-specific antibody responses. Multivariate statistical methods were employed using T and B cell immune phenotypic profiles obtained with cells from several tissues of individual mice. The data was used to identify combinations of markers that could predict an HCMV infection vs. reactivation status. In spleen, but not in lymph nodes, higher frequencies of effector CD4+ T cells expressing PD-1 were among the factors most suited to distinguish HCMV reactivations from infections. These results suggest a shift from a T cell dominated immune response during latent infections toward an exhausted T cell phenotype and active humoral immune response upon reactivations. In sum, this novel in vivo humanized model combined with advanced analyses highlights a dynamic system clearly specifying the immunological spatial signatures of HCMV latency and reactivations. These signatures can be merged as predictive biomarker clusters that can be applied in the clinical translation of new therapies for the control of HCMV reactivation.
Frontiers
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
B cell class switch
fd49f527-b3df-41e2-aa71-7d7638eaa851
HCMV
21c564d2-5d2f-488e-95e0-10ef75e5ae74
T cell maturation
aa3d85a0-4993-4f08-a8f9-c29972c57d76
humanized mice
5c0a1396-9154-4808-ba9e-e19a9d060938
500
linear discriminant analyses
29d36041-231a-4876-989f-87ebdfd1f212
optical imaging analyses
c2bd693d-c78b-487e-b7eb-58641e4ccfb4
principal component analyses
a0eda716-0e3d-4091-8b4c-4943a2b24011
reactivation
c6b7e450-a54a-4fce-b408-b8281d6e825d
Signatures of T and B Cell Development, Functional Responses and PD-1 Upregulation After HCMV Latent Infections and Reactivations in Nod.Rag.Gamma Mice Humanized With Cord Blood CD34 Cells.
Article
Frontiers in immunology
2019-01-15T13:45:27Z
THUMBNAIL
Theobald et al.pdf.jpg
Theobald et al.pdf.jpg
Generated Thumbnail
image/jpeg
141632
https://hzi.openrepository.com/bitstream/10033/621648/5/Theobald%20et%20al.pdf.jpg
51312f88af5eb74ed8ca6895fe7bf96f
MD5
5
false
TEXT
Theobald et al.pdf.txt
Theobald et al.pdf.txt
Extracted text
text/plain
103558
https://hzi.openrepository.com/bitstream/10033/621648/4/Theobald%20et%20al.pdf.txt
2457b7300765de2188b34bcb05818dda
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621648/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621648/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Theobald et al.pdf
Theobald et al.pdf
Open Access publication
application/pdf
5260272
https://hzi.openrepository.com/bitstream/10033/621648/1/Theobald%20et%20al.pdf
aa670fd4b031a15765e5dd3fbc0b87ba
MD5
1
true
10033/621648
oai:hzi.openrepository.com:10033/621648
2019-08-30 11:33:54.946
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6217482019-08-30T11:32:11Zcom_10033_620659col_10033_620660
Siokis, Anastasios
a874c68d3386019489682d501c19027a
500
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Demetriou, Philippos
e94c818d5e6829a63beddc6a29d2176e
500
Dustin, Michael L
ac13dfbdd962c435ae8154c76ebb5bd1
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-04-16T08:45:31Z
2019-04-16T08:45:31Z
2018-07-31
Cell Rep. 2018 Jul 31;24(5):1151-1162. doi: 10.1016/j.celrep.2018.06.114
2211-1247
30067972
10.1016/j.celrep.2018.06.114
http://hdl.handle.net/10033/621748
Cell Reports
During immunological synapse (IS) formation, T cell receptor (TCR) signaling complexes, integrins, and costimulatory molecules exhibit a particular spatial localization. Here, we develop an agent-based model for the IS formation based on TCR peptide-bound major histocompatibility complex (pMHC) and leukocyte-function-associated antigen 1 (LFA-1) intracellular activation molecule 1 (ICAM-1) dynamics, including CD28 binding to a costimulatory ligand, coupling of molecules to the centripetal actin flow, and size-based segregation (SBS). A radial gradient of LFA-1 in the peripheral supramolecular activation cluster (pSMAC) toward the central supramolecular activation cluster (cSMAC) emerged as a combined consequence of actin binding and diffusion and modified the positioning of other molecules. The simulations predict a mechanism of CD28 movement, according to which CD28-CD80 complexes passively follow TCR-pMHC microclusters. However, the characteristic CD28-CD80 localization in a ring pattern around the cSMAC only emerges with a particular CD28-actin coupling strength that induces a centripetal motion. These results have implications for the understanding of T cell activation and fate decisions.
en
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
CD28
6e50227c-d950-4863-b17d-1800c15f1377
F-actin flow
16a801d4-b0dc-40d3-8ebc-f94738bed857
agent-based modeling
3223971c-1874-4f5e-a831-78b85c837c58
immulogical synapse
dd35b0be-9dcf-46dc-91a4-7893aa487ec9
molecular transport
72c375d4-2d29-447e-b007-57d644fe1bbd
pattern formation
da838f73-c00c-410a-b70a-817d34beac4c
F-Actin-Driven CD28-CD80 Localization in the Immune Synapse.
Article
Cell reports
2019-04-16T08:45:32Z
THUMBNAIL
Siokis et al.pdf.jpg
Siokis et al.pdf.jpg
Generated Thumbnail
image/jpeg
84306
https://hzi.openrepository.com/bitstream/10033/621748/5/Siokis%20et%20al.pdf.jpg
ebbdc65e74b31b9045fa89c9da1fa33d
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
47107
https://hzi.openrepository.com/bitstream/10033/621748/6/elsevier-thumbnail.png
cf0ce83a35e981759ef595ea5473a832
MD5
6
false
TEXT
Siokis et al.pdf.txt
Siokis et al.pdf.txt
Extracted text
text/plain
57522
https://hzi.openrepository.com/bitstream/10033/621748/4/Siokis%20et%20al.pdf.txt
a24acacbdd94584794402917737f6045
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621748/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621748/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Siokis et al.pdf
Siokis et al.pdf
Open Access publication
application/pdf
4586642
https://hzi.openrepository.com/bitstream/10033/621748/1/Siokis%20et%20al.pdf
e31b56e733922f4bf2e3b82785a5b739
MD5
1
true
10033/621748
oai:hzi.openrepository.com:10033/621748
2019-08-30 11:32:11.603
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6217892019-11-21T12:10:44Zcom_10033_620659col_10033_620660
Schlicker, Lisa
248d6880be84e460ea2981612669aa36
500
Boers, Hanny M
28e20b0cfb39ca5f82ee822d7384059c
500
Dudek, Christian-Alexander
2285eb47664f30397e95d9de01878239
500
Zhao, Gang
37ec65924f58972f17d1469d470e37d8
500
Barua, Arnab
e5233ccc288d2dd0de9728c41dcbaf04
500
Trezzi, Jean-Pierre
a308e6ec7f22bd4ebcdd1025061b7991
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Jacobs, Doris M
bbb06dd588f6050f66d72614603a140e
500
Hiller, Karsten
e9d523d0ef295fcf54bedfaaf7ac58d9
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-05-21T11:38:35Z
2019-05-21T11:38:35Z
2019-05-07
Metabolites. 2019 May 7;9(5). pii: metabo9050091. doi: 10.3390/metabo9050091.
2218-1989
31067731
10.3390/metabo9050091
http://hdl.handle.net/10033/621789
Metabolites
Food supplementation with a fiber mix of guar gum and chickpea flour represents a promising approach to reduce the risk of type 2 diabetes mellitus (T2DM) by attenuating postprandial glycemia. To investigate the effects on postprandial metabolic fluxes of glucose-derived metabolites in response to this fiber mix, a randomized, cross-over study was designed. Twelve healthy, male subjects consumed three different flatbreads either supplemented with 2% guar gum or 4% guar gum and 15% chickpea flour or without supplementation (control). The flatbreads were enriched with ~2% of 13C-labeled wheat flour. Blood was collected at 16 intervals over a period of 360 min after bread intake and plasma samples were analyzed by GC-MS based metabolite profiling combined with stable isotope-assisted metabolomics. Although metabolite levels of the downstream metabolites of glucose, specifically lactate and alanine, were not altered in response to the fiber mix, supplementation of 4% guar gum was shown to significantly delay and reduce the exogenous formation of these metabolites. Metabolic modeling and computation of appearance rates revealed that the effects induced by the fiber mix were strongest for glucose and attenuated downstream of glucose. Further investigations to explore the potential of fiber mix supplementation to counteract the development of metabolic diseases are warranted.
en
MPDI
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
13C-enrichment
ee3d0c28-5450-4888-8917-0c13c9a5ca69
GC-MS
6e8917c8-e399-4d5b-8ce4-1d7df48c993e
chickpea flour
599215e7-713d-4e63-bf41-49fbf4467af4
guar gum
17478f8a-1f21-4ee6-9af1-b6f15e37301b
metabolism
88ddcda1-8450-46c2-ab7c-dce0269b44a2
starch
33d40526-1d99-41c6-af72-7ba25d09d811
wheat flour
67025d13-f49c-4326-aeaf-168c16c86b4d
Postprandial Metabolic Effects of Fiber Mixes Revealed by in vivo Stable Isotope Labeling in Humans.
Article
Metabolites
2019-05-21T11:38:35Z
THUMBNAIL
Schlicker et al.pdf.jpg
Schlicker et al.pdf.jpg
Generated Thumbnail
image/jpeg
92477
https://repository.helmholtz-hzi.de/bitstream/10033/621789/5/Schlicker%20et%20al.pdf.jpg
a0f2e94fa799c89bd4dc6975a8c5f659
MD5
5
false
TEXT
Schlicker et al.pdf.txt
Schlicker et al.pdf.txt
Extracted text
text/plain
76781
https://repository.helmholtz-hzi.de/bitstream/10033/621789/4/Schlicker%20et%20al.pdf.txt
4e156cd38d4426bf06ea320d6cf485bd
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/621789/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/621789/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Schlicker et al.pdf
Schlicker et al.pdf
Open Access publication
application/pdf
2528523
https://repository.helmholtz-hzi.de/bitstream/10033/621789/1/Schlicker%20et%20al.pdf
08c8e3e2a9abb4cd2fcef08729407cbc
MD5
1
true
10033/621789
oai:repository.helmholtz-hzi.de:10033/621789
2019-11-21 12:10:44.637
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6218302019-08-30T11:32:13Zcom_10033_620659col_10033_620660
Alfonso, J C L
a51e61d7b90ab4d2488910e20fe1811c
600
http://orcid.org/0000-0002-9005-6897
Berk, L
6438b0990498c0acdb751ccb8309a18f
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-06-26T13:05:29Z
2019-06-26T13:05:29Z
2019-05-30
Radiat Oncol. 2019 May 30;14(1):88. doi: 10.1186/s13014-019-1288-y.
1748-717X
31146751
10.1186/s13014-019-1288-y
http://hdl.handle.net/10033/621830
Radiation Oncology
Standard radiobiology theory of radiation response assumes a uniform innate radiosensitivity of tumors. However, experimental data show that there is significant intratumoral heterogeneity of radiosensitivity. Therefore, a model with heterogeneity was developed and tested using existing experimental data to show the potential effects from the presence of an intratumoral distribution of radiosensitivity on radiation therapy response over a protracted radiation therapy treatment course.
en
BioMed Central (BMC)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Accelerated repopulation
29f3c533-46c7-4e42-89ef-c84913948636
Fractionated radiotherapy
2bc61e27-1db9-42c0-82b7-fc983cd433d3
Intratumoral radiosensitivity heterogeneity
6eacd8b8-ee7f-4ff8-8954-4b029407723a
Linear-quadratic model
7d9e25c7-4dac-4b0d-ad6d-35197033905a
Radiation resistance
e738aad2-adb0-4e3b-a051-3bd0de5eba85
Modeling the effect of intratumoral heterogeneity of radiosensitivity on tumor response over the course of fractionated radiation therapy.
Article
Radiation oncology (London, England)
2019-06-26T13:05:29Z
THUMBNAIL
Alfonso and Berk.pdf.jpg
Alfonso and Berk.pdf.jpg
Generated Thumbnail
image/jpeg
101883
https://hzi.openrepository.com/bitstream/10033/621830/5/Alfonso%20and%20Berk.pdf.jpg
51d2f812b633689dd7b904a114d34ffe
MD5
5
false
TEXT
Alfonso and Berk.pdf.txt
Alfonso and Berk.pdf.txt
Extracted text
text/plain
50450
https://hzi.openrepository.com/bitstream/10033/621830/4/Alfonso%20and%20Berk.pdf.txt
80b27d31298d72034ac3650c1904a0ca
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621830/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621830/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Alfonso and Berk.pdf
Alfonso and Berk.pdf
Open Access publication
application/pdf
2696614
https://hzi.openrepository.com/bitstream/10033/621830/1/Alfonso%20and%20Berk.pdf
2b31748c384dff310e30215e74db67cb
MD5
1
true
10033/621830
oai:hzi.openrepository.com:10033/621830
2019-08-30 11:32:13.406
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6218592019-08-30T11:26:40Zcom_10033_620659col_10033_620660
Mascheroni, Pietro
f046cc349bd1d2fe247ffdccdb2b8d21
500
López Alfonso, Juan Carlos
9424f8eee94aa0a45a9effdea53f09ee
500
Kalli, Maria
f39547d87b48050438986175efecf2f8
500
Stylianopoulos, Triantafyllos
097a3e9192cc736f26a1e761ad8a6235
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2019-07-11T09:33:40Z
2019-07-11T09:33:40Z
2019-05-24
Cancers (Basel). 2019 May 24;11(5). pii: cancers11050716. doi: 10.3390/cancers11050716.
2072-6694
31137643
10.3390/cancers11050716
http://hdl.handle.net/10033/621859
Cancers
Tumor microenvironment is a critical player in glioma progression, and novel therapies for its targeting have been recently proposed. In particular, stress-alleviation strategies act on the tumor by reducing its stiffness, decreasing solid stresses and improving blood perfusion. However, these microenvironmental changes trigger chemo–mechanically induced cellular phenotypic transitions whose impact on therapy outcomes is not completely understood. In this work we analyze the effects of mechanical compression on migration and proliferation of glioma cells. We derive a mathematical model of glioma progression focusing on cellular phenotypic plasticity. Our results reveal a trade-off between tumor infiltration and cellular content as a consequence of stress-alleviation approaches. We discuss how these novel findings increase the current understanding of glioma/microenvironment interactions and can contribute to new strategies for improved therapeutic outcomes. View Full-Text
MPDI
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
glioma
phenotypic transitions
solid stress
stress-alleviation therapy
On the Impact of Chemo-Mechanically Induced Phenotypic Transitions in Gliomas.
Article
Cancers
2019-07-11T09:33:40Z
THUMBNAIL
Mascheroni et al.pdf.jpg
Mascheroni et al.pdf.jpg
Generated Thumbnail
image/jpeg
90431
https://hzi.openrepository.com/bitstream/10033/621859/5/Mascheroni%20et%20al.pdf.jpg
fa98c90ae1fc164f928d49110c8dc420
MD5
5
false
TEXT
Mascheroni et al.pdf.txt
Mascheroni et al.pdf.txt
Extracted text
text/plain
73788
https://hzi.openrepository.com/bitstream/10033/621859/4/Mascheroni%20et%20al.pdf.txt
637525ad245c78f512d53fc4da9b37c3
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621859/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621859/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Mascheroni et al.pdf
Mascheroni et al.pdf
Open Access publication
application/pdf
4799297
https://hzi.openrepository.com/bitstream/10033/621859/1/Mascheroni%20et%20al.pdf
0f3fdce6a66f03a6b56acbe3da330b78
MD5
1
true
10033/621859
oai:hzi.openrepository.com:10033/621859
2019-08-30 11:26:40.021
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6218852019-08-30T11:26:41Zcom_10033_620659col_10033_620660
Cañete, Pablo F
e8d235a53e3419d4f426e15a4962cb29
500
Sweet, Rebecca A
27adce65e1207c7bebeced9ba28143c4
500
Gonzalez-Figueroa, Paula
9adf1abfde818dc8a352a614d93237da
500
Papa, Ilenia
d741abfb91c1fdd9d0f7d5d519fda58f
500
Ohkura, Naganari
9bec8c46de038f72c88ce107cc6a263f
500
Bolton, Holly
9bb0ce1e6b2aa5288276f25e33143b27
500
Roco, Jonathan A
244e53f60d54e16e956e0811ff8459fa
500
Cuenca, Marta
71df784feb8255a91456d586006bc9fe
500
Bassett, Katharine J
6389f4a63ce90a42dd89efb8f433e983
500
Sayin, Ismail
aab04013e7e5f2897ef4b2823ccdb3ae
500
Barry, Emma
54d2f7d9f5d801f3c8f92bc2ab1c830d
500
Lopez, Angel
9aac72e34fdcacb955cec492f0883ce1
500
Canaday, David H
a05951f251ca1da6f352bebae1e7dfbc
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Doglioni, Claudio
ae7562a8cc3f9e9799ba6371ab69e255
500
Fazekas de St Groth, Barbara
0aa47faf4205f401803c78938ef6170c
500
Sakaguchi, Shimon
c60333163adf559291f89ca3e68dc2e7
500
Cook, Matthew C
8f0bdeac938c0640f59e9d4e87897a7d
500
Vinuesa, Carola G
42fa15969b639d7015cf90f87c78dd6f
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-07-19T10:12:00Z
2019-07-19T10:12:00Z
2019-06-17
J Exp Med. 2019 Jun 17. pii: jem.20190493. doi: 10.1084/jem.20190493.
1540-9538
31209070
10.1084/jem.20190493
http://hdl.handle.net/10033/621885
Journal of experimental Medicine
Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell-derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell-derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10-producing TF cells but not with total T reg cells, TFR, or IL-10-producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.
en
Rockefeller University Press
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Regulatory roles of IL-10-producing human follicular T cells.
Article
The Journal of experimental medicine
2019-07-19T10:12:01Z
THUMBNAIL
Canete et al.pdf.jpg
Canete et al.pdf.jpg
Generated Thumbnail
image/jpeg
124744
https://hzi.openrepository.com/bitstream/10033/621885/5/Canete%20et%20al.pdf.jpg
0c33760424ec5ff966518003beca04d6
MD5
5
false
TEXT
Canete et al.pdf.txt
Canete et al.pdf.txt
Extracted text
text/plain
71021
https://hzi.openrepository.com/bitstream/10033/621885/4/Canete%20et%20al.pdf.txt
c24bf93a55c7089fbce55e5d4a32e0fa
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621885/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621885/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Canete et al.pdf
Canete et al.pdf
Open Access article
application/pdf
3141020
https://hzi.openrepository.com/bitstream/10033/621885/1/Canete%20et%20al.pdf
395dcf827b62782d1f2404a91750eef1
MD5
1
true
10033/621885
oai:hzi.openrepository.com:10033/621885
2019-08-30 11:26:41.245
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6219202019-08-30T11:24:30Zcom_10033_620659col_10033_620660
Enderling, Heiko
ce54ce9a2a33d863166374b0cc76ae60
500
Alfonso, Juan Carlos López
111f7079156479cfa5feaa2c5d6e1be7
Moros, Eduardo
e46e017dbe5287ccd3be1e5eebff139d
500
Caudell, Jimmy J.
4354b74b344e8d9326354c787db48339
500
Harrison, Louis B.
9ca4862e1e7f491b8b9b96ee251852ed
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
Enderling, H.
2019-08-27T09:13:23Z
2019-08-27T09:13:23Z
2019-08-01
24058033
10.1016/j.trecan.2019.06.006
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068509350&origin=inward
http://hdl.handle.net/10033/621920
Trends in Cancer
2-s2.0-85068509350
2-s2.0-85059309527
SCOPUS_ID:85068509350
S2405803319301256
In current radiation oncology practice, treatment protocols are prescribed based on the average outcomes of large clinical trials, with limited personalization and without adaptations of dose or dose fractionation to individual patients based on their individual clinical responses. Predicting tumor responses to radiation and comparing predictions against observed responses offers an opportunity for novel treatment evaluation. These analyses can lead to protocol adaptation aimed at the improvement of patient outcomes with better therapeutic ratios. We foresee the integration of mathematical models into radiation oncology to simulate individual patient tumor growth and predict treatment response as dynamic biomarkers for personalized adaptive radiation therapy (RT).
en
Elsevier(Cell Press)
Trends in Cancer
8
5
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
adaptive therapy
mathematical oncology
radiation
radiotherapy
systems medicine
Integrating Mathematical Modeling into the Roadmap for Personalized Adaptive Radiation Therapy
Article
THUMBNAIL
2020-07-10
Enderling et al.pdf.jpg
Enderling et al.pdf.jpg
Generated Thumbnail
image/jpeg
40240
https://hzi.openrepository.com/bitstream/10033/621920/7/Enderling%20et%20al.pdf.jpg
14faa58ceb33de8cad1d399ede982590
MD5
7
false
2020-07-10
Enderling-Fig1.tif.jpg
Enderling-Fig1.tif.jpg
IM Thumbnail
image/jpeg
12484
https://hzi.openrepository.com/bitstream/10033/621920/8/Enderling-Fig1.tif.jpg
7797f34d8404b42cf86654b1ba00768d
MD5
8
false
2020-07-10
Enderling-Fig2.tif.jpg
Enderling-Fig2.tif.jpg
IM Thumbnail
image/jpeg
15019
https://hzi.openrepository.com/bitstream/10033/621920/9/Enderling-Fig2.tif.jpg
99aba6d535031a9df68a38de9d1063f8
MD5
9
false
elsevier-thumbnail.png
application/octet-stream
60832
https://hzi.openrepository.com/bitstream/10033/621920/10/elsevier-thumbnail.png
6af8ff0a1de543e250882268c533c939
MD5
10
false
TEXT
2020-07-10
Enderling et al.pdf.txt
Enderling et al.pdf.txt
Extracted text
text/plain
34794
https://hzi.openrepository.com/bitstream/10033/621920/6/Enderling%20et%20al.pdf.txt
b503f498568f86de76dc8a5b3d2b46a2
MD5
6
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621920/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621920/4/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
4
false
ORIGINAL
Enderling et al.pdf
Enderling et al.pdf
original manuscript
application/pdf
585044
https://hzi.openrepository.com/bitstream/10033/621920/1/Enderling%20et%20al.pdf
80209eeead167344c6633b303c25f97d
MD5
1
true
Enderling-Fig1.tif
Enderling-Fig1.tif
figure 1
image/tiff
119843
https://hzi.openrepository.com/bitstream/10033/621920/2/Enderling-Fig1.tif
37e1c00a58d33c1f0d0297c8de87f026
MD5
2
false
Enderling-Fig2.tif
Enderling-Fig2.tif
figure 2
image/tiff
278769
https://hzi.openrepository.com/bitstream/10033/621920/3/Enderling-Fig2.tif
037ef56a860da63e757525193e2cbce7
MD5
3
false
10033/621920
oai:hzi.openrepository.com:10033/621920
2019-08-30 11:24:30.969
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6219262019-09-04T01:34:46Zcom_10033_620659col_10033_620660
López Alfonso, Juan Carlos
9424f8eee94aa0a45a9effdea53f09ee
Poleszczuk, Jan
412361dcf3aa990417460b42bc64a4b4
300
Walker, Rachel
7b6ea387c950bfe218c5c8393a947f20
300
Kim, Sungjune
fa4f6549e87f275a63a6f0f53d766d14
300
Pilon-Thomas, Shari
3a1e6c74ffcc02211a6ed89ac432c580
300
Conejo-Garcia, Jose J
07ff1404550c384dc141377e59196239
300
Soliman, Hatem
8e68f6b380ff0c049270fc35b43f2549
300
Czerniecki, Brian
632297d8751414708d2043ce02d5142a
300
Harrison, Louis B
3a12cc3cad4edcb79a31b0eb0d000539
Enderling, Heiko
ce54ce9a2a33d863166374b0cc76ae60
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-09-03T08:40:40Z
2019-09-03T08:40:40Z
2019-01-01
JCO Clin Cancer Inform. 2019 Apr;3:1-16. doi: 10.1200/CCI.18.00075.
2473-4276
30964698
10.1200/CCI.18.00075
http://hdl.handle.net/10033/621926
JCO Clinical Cancer Informatics
PURPOSE Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy
before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and diseasefree survival (DFS) with SR and RS for different cancer types and simulate the plausibility of RS- and SR-induced
antitumor immunity contributing to outcomes.
MATERIALS AND METHODS We analyzed a SEER data set of early-stage cancers treated with SR or RS. OS and
DFS were calculated for cancers with sufficient numbers for statistical power (cancers of lung and bronchus,
esophagus, rectum, cervix uteri, corpus uteri, and breast). We simulated the immunologic consequences of SR,
RS, and radiotherapy alone in a mathematical model of tumor-immune interactions.
RESULTS RS improved OS for cancers with low 20-year survival rates (lung: hazard ratio [HR], 0.88; P = .046)
and improved DFS for cancers with higher survival (breast: HR = 0.64; P , .001). For rectal cancer, with
intermediate 20-year survival, RS improved both OS (HR = 0.89; P = .006) and DFS (HR = 0.86; P = .04).
Model simulations suggested that RS could increase OS by eliminating cancer for a broader range of model
parameters and radiotherapy-induced antitumor immunity compared with SR for selected parameter
combinations. This could create an immune memory that may explain increased DFS after RS for certain
cancers.
CONCLUSION Study results suggest plausibility that radiation to the bulk of the tumor could induce a more robust
immune response and better harness the synergy of radiotherapy and antitumor immunity than postsurgical
radiation to the tumor bed. This exploratory study provides motivation for prospective evaluation of immune
activation of RS versus SR in controlled clinical studies
en
American Society of Clinical Oncology
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Immunologic Consequences of Sequencing Cancer Radiotherapy and Surgery.
Article
JCO clinical cancer informatics
THUMBNAIL
2020-04-09
Alfonso et al.pdf.jpg
Alfonso et al.pdf.jpg
Generated Thumbnail
image/jpeg
115720
https://hzi.openrepository.com/bitstream/10033/621926/5/Alfonso%20et%20al.pdf.jpg
2005abd8232f5e801350cba3d253d629
MD5
5
false
TEXT
2020-04-09
Alfonso et al.pdf.txt
Alfonso et al.pdf.txt
Extracted text
text/plain
57882
https://hzi.openrepository.com/bitstream/10033/621926/4/Alfonso%20et%20al.pdf.txt
1d8048b03aa13d0e0514d03839be7615
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621926/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621926/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Alfonso et al.pdf
Alfonso et al.pdf
allowed publisher' PDF
application/pdf
1460138
https://hzi.openrepository.com/bitstream/10033/621926/1/Alfonso%20et%20al.pdf
ad206d5fdd2806eaa3c353101f5a03c1
MD5
1
true
10033/621926
oai:hzi.openrepository.com:10033/621926
2019-09-04 01:34:46.523
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6219512019-09-20T01:28:29Zcom_10033_620659col_10033_620660
Schaadt, Nadine S
938c01124f74cc5700c9ca63259f2e44
300
Alfonso, Juan Carlos López
111f7079156479cfa5feaa2c5d6e1be7
500
Schönmeyer, Ralf
2274eb555c88410afaf7d3cf38fc59b2
300
Grote, Anne
024b150fcc063e924c2de2c17d1d288e
300
Forestier, Germain
1c83da123f97ceaf3056f5979abab76c
300
Wemmert, Cédric
6a962bc330fb0b0e37b3b88f02294c59
300
Krönke, Nicole
00b68e3ef0498c657651d475c7094a3b
300
Stoeckelhuber, Mechthild
e63605c4e49f370f6069fb0ba9faeab3
300
Kreipe, Hans H
7a9b02db67ad7dc9d6efb35ea8c65c41
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Feuerhake, Friedrich
4809c83e5163d63484ac91dc1517b5a2
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-09-19T12:06:41Z
2019-09-19T12:06:41Z
2017-07-01
Breast Cancer Res Treat. 2017 Jul;164(2):305-315. doi: 10.1007/s10549-017-4239-z. Epub 2017 Apr 25.
1573-7217
28444535
10.1007/s10549-017-4239-z
http://hdl.handle.net/10033/621951
Brest cancer research and treatment
Purpose: To improve microscopic evaluation of immune cells relevant in breast cancer oncoimmunology, we aim at distinguishing normal infiltration patterns from lymphocytic lobulitis by advanced image analysis. We consider potential immune cell variations due to the menstrual cycle and oral contraceptives in non-neoplastic mammary gland tissue.
METHODS:
Lymphocyte and macrophage distributions were analyzed in the anatomical context of the resting mammary gland in immunohistochemically stained digital whole slide images obtained from 53 reduction mammoplasty specimens. Our image analysis workflow included automated regions of interest detection, immune cell recognition, and co-registration of regions of interest.
RESULTS:
In normal lobular epithelium, seven CD8[Formula: see text] lymphocytes per 100 epithelial cells were present on average and about 70% of this T-lymphocyte population was lined up along the basal cell layer in close proximity to the epithelium. The density of CD8[Formula: see text] T-cell was 1.6 fold higher in the luteal than in the follicular phase in spontaneous menstrual cycles and 1.4 fold increased under the influence of oral contraceptives, and not co-localized with epithelial proliferation. CD4[Formula: see text] T-cells were infrequent. Abundant CD163[Formula: see text] macrophages were widely spread, including the interstitial compartment, with minor variation during the menstrual cycle.
CONCLUSIONS:
Spatial patterns of different immune cell subtypes determine the range of normal, as opposed to inflammatory conditions of the breast tissue microenvironment. Advanced image analysis enables quantification of hormonal effects, refines lymphocytic lobulitis, and shows potential for comprehensive biopsy evaluation in oncoimmunolog
en
Springer
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Digital pathology
Hormonal fluctuations
Lymphocytic lobulitis
Menstrual cycle
Object-based image analysis
Oncoimmunology
Image analysis of immune cell patterns in the human mammary gland during the menstrual cycle refines lymphocytic lobulitis.
Article
Breast cancer research and treatment
2019-09-19T12:06:42Z
THUMBNAIL
Schaadt et al.pdf.jpg
Schaadt et al.pdf.jpg
Generated Thumbnail
image/jpeg
80887
https://hzi.openrepository.com/bitstream/10033/621951/5/Schaadt%20et%20al.pdf.jpg
043d169e2734b8c1cb270596a4a437b0
MD5
5
false
TEXT
Schaadt et al.pdf.txt
Schaadt et al.pdf.txt
Extracted text
text/plain
45159
https://hzi.openrepository.com/bitstream/10033/621951/4/Schaadt%20et%20al.pdf.txt
abd1ac5641bf4a03613cbcb5314168d1
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621951/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621951/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Schaadt et al.pdf
Schaadt et al.pdf
final manuscript
application/pdf
2374886
https://hzi.openrepository.com/bitstream/10033/621951/1/Schaadt%20et%20al.pdf
52d8759a41bdc864d1cd313e7b459d5a
MD5
1
true
10033/621951
oai:hzi.openrepository.com:10033/621951
2019-09-20 01:28:29.121
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6219812019-10-18T02:43:55Zcom_10033_620659col_10033_620660
Arulraj, Theinmozhi
7f81f4a361c7601256a026aefaf11acd
300
Binder, Sebastian C
ca9fc32341dea761712a6ca7f0d7308b
600
http://orcid.org/0000-0003-1169-1786
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-10-17T10:56:26Z
2019-10-17T10:56:26Z
2019-01-01
Front Immunol. 2019 Sep 6;10:2116. doi: 10.3389/fimmu.2019.02116. eCollection 2019.
1664-3224
31555300
10.3389/fimmu.2019.02116
http://hdl.handle.net/10033/621981
Frontiers in Immunology
The germinal center reaction is an important target for modulating antibody responses. Antibody production from germinal centers is regulated by a negative feedback mechanism termed antibody feedback. By imposing antibody feedback, germinal centers can interact and regulate the output of other germinal centers. Using an agent-based model of the germinal center reaction, we studied the impact of antibody feedback on kinetics and efficiency of a germinal center. Our simulations predict that high feedback of antibodies from germinal centers reduces the production of plasma cells and subsequently the efficiency of the germinal center reaction by promoting earlier termination. Affinity maturation is only weakly improved by increased antibody feedback and ultimately interrupted because of premature termination of the reaction. The model predicts that the asynchronous onset and changes in number of germinal centers could alter the efficiency of antibody response due to changes in feedback by soluble antibodies. Consequently, late initialized germinal centers have a compromised output due to higher antibody feedback from the germinal centers formed earlier. The results demonstrate potential effects of germinal center intercommunication and highlight the importance of understanding germinal center interactions for optimizing the antibody response, in particular, in the elderly and in the context of vaccination.
en
Frontiers
info:eu-repo/grantAgreement/EC/H2020/ 765158
openAccess
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
antibody production
computer simulation
germinal center
mathematical modeling
vaccination
Synchronous Germinal Center Onset Impacts the Efficiency of Antibody Responses.
Article
Frontiers in immunology
2019-10-17T10:56:27Z
THUMBNAIL
Arulraj et al.pdf.jpg
Arulraj et al.pdf.jpg
Generated Thumbnail
image/jpeg
123743
https://hzi.openrepository.com/bitstream/10033/621981/5/Arulraj%20et%20al.pdf.jpg
2cecbd3acf1ad1217cffdcbc7011cf48
MD5
5
false
TEXT
Arulraj et al.pdf.txt
Arulraj et al.pdf.txt
Extracted text
text/plain
35614
https://hzi.openrepository.com/bitstream/10033/621981/4/Arulraj%20et%20al.pdf.txt
62ecdd22b4af73b03ce82a0841e965ac
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://hzi.openrepository.com/bitstream/10033/621981/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://hzi.openrepository.com/bitstream/10033/621981/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Arulraj et al.pdf
Arulraj et al.pdf
Open Access publication
application/pdf
777089
https://hzi.openrepository.com/bitstream/10033/621981/1/Arulraj%20et%20al.pdf
401079a06561856ddcf8528ee1088eb3
MD5
1
true
10033/621981
oai:hzi.openrepository.com:10033/621981
2019-10-18 02:43:55.08
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6220192019-11-20T02:02:36Zcom_10033_620659col_10033_620660
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2019-11-19T14:59:46Z
2019-11-19T14:59:46Z
2019-10-29
Cell Rep. 2019 Oct 29;29(5):1066-1073.e5. doi: 10.1016/j.celrep.2019.09.058.
2211-1247
31665624
10.1016/j.celrep.2019.09.058
http://hdl.handle.net/10033/622019
Cell Reports
Broadly neutralizing antibodies are crucial for the control of many life-threatening viral infections like HIV, influenza, or hepatitis. Their induction is a prime goal in vaccine research. Using computer simulations, we identify strategies to promote the generation of broadly neutralizing antibodies in natural germinal center (GC) reactions. The simulations predict a feedback loop based on antibodies and memory B cells from previous GC reactions that promotes GCs to focus on new epitopes. Memory-derived or injected antibodies specific for immunodominant epitopes control epitope availability, suppress the participation of memory B cells in the GC reaction, and allow for the evolution of other B cells to affinity mature for hidden or rare epitopes. This defines a natural selection mechanism for GC B cells to concentrate on new epitopes rather than refine affinity to already-covered epitopes. This principle can be used for the design and testing of future therapies and vaccination protocols.
en
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
HIV
broadly neutralizing antibodies
germinal center
hepatitis
influenza
mathematical modeling
memory B cells
original antigenic sin
simulation
targeting hidden epitopes
Injection of Antibodies against Immunodominant Epitopes Tunes Germinal Centers to Generate Broadly Neutralizing Antibodies.
Article
Cell reports
2019-11-19T14:59:47Z
THUMBNAIL
Meyer-Hermann.pdf.jpg
Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
100228
https://repository.helmholtz-hzi.de/bitstream/10033/622019/5/Meyer-Hermann.pdf.jpg
3ea5c31d54fe84c8f1a1b97c557a860c
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
47814
https://repository.helmholtz-hzi.de/bitstream/10033/622019/6/elsevier-thumbnail.png
5fa7e27719c9d9ac16aeeba460003e48
MD5
6
false
TEXT
Meyer-Hermann.pdf.txt
Meyer-Hermann.pdf.txt
Extracted text
text/plain
62568
https://repository.helmholtz-hzi.de/bitstream/10033/622019/4/Meyer-Hermann.pdf.txt
e6cd0ed5bbbc1b4224b83e8e92ea72fd
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622019/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622019/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Meyer-Hermann.pdf
Meyer-Hermann.pdf
Open Access publication
application/pdf
1939189
https://repository.helmholtz-hzi.de/bitstream/10033/622019/1/Meyer-Hermann.pdf
15a197f024663a2a82eddaf7497d2fa9
MD5
1
true
10033/622019
oai:repository.helmholtz-hzi.de:10033/622019
2019-11-20 02:02:36.888
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6221912020-04-07T05:15:09Zcom_10033_620659col_10033_620660
Schaadt, Nadine S
938c01124f74cc5700c9ca63259f2e44
500
Schönmeyer, Ralf
2274eb555c88410afaf7d3cf38fc59b2
500
Forestier, Germain
1c83da123f97ceaf3056f5979abab76c
500
Brieu, Nicolas
bd8e8b087a880030cb31e98450188257
300
Braubach, Peter
3a295ca0803c33fc24e4e78a3a45872b
500
Nekolla, Katharina
b2a481d08d4c4cd17db8eb3fba109ff8
300
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Feuerhake, Friedrich
4809c83e5163d63484ac91dc1517b5a2
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-03-06T10:51:43Z
2020-03-06T10:51:43Z
2020-02-01
PLoS Comput Biol. 2020 Feb 21;16(2):e1007385. doi: 10.1371/journal.pcbi.1007385. eCollection 2020 Feb.
1553-7358
32084130
10.1371/journal.pcbi.1007385
http://hdl.handle.net/10033/622191
PLOS computational biology
Our aim is to complement observer-dependent approaches of immune cell evaluation in microscopy images with reproducible measures for spatial composition of lymphocytic infiltrates. Analyzing such patterns of inflammation is becoming increasingly important for therapeutic decisions, for example in transplantation medicine or cancer immunology. We developed a graph-based assessment of lymphocyte clustering in full whole slide images. Based on cell coordinates detected in the full image, a Delaunay triangulation and distance criteria are used to build neighborhood graphs. The composition of nodes and edges are used for classification, e.g. using a support vector machine. We describe the variability of these infiltrates on CD3/CD20 duplex staining in renal biopsies of long-term functioning allografts, in breast cancer cases, and in lung tissue of cystic fibrosis patients. The assessment includes automated cell detection, identification of regions of interest, and classification of lymphocytic clusters according to their degree of organization. We propose a neighborhood feature which considers the occurrence of edges with a certain type in the graph to distinguish between phenotypically different immune infiltrates. Our work addresses a medical need and provides a scalable framework that can be easily adjusted to the requirements of different research questions.
en
PLOS
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
B cells
Graphs
T cells
immune cells
dentritic structure
pathologists
lymphocytes
support vector machines
Graph-based description of tertiary lymphoid organs at single-cell level.
Article
PLoS computational biology
2020-03-06T10:51:44Z
THUMBNAIL
Schaadt et al.pdf.jpg
Schaadt et al.pdf.jpg
Generated Thumbnail
image/jpeg
103371
https://repository.helmholtz-hzi.de/bitstream/10033/622191/9/Schaadt%20et%20al.pdf.jpg
09f54039bbb5c859f4248b803651381f
MD5
9
false
Schaadt_appendix S1.pdf.jpg
Schaadt_appendix S1.pdf.jpg
Generated Thumbnail
image/jpeg
31780
https://repository.helmholtz-hzi.de/bitstream/10033/622191/10/Schaadt_appendix%20S1.pdf.jpg
3469f659c5e5108864510fa9a7c1585c
MD5
10
false
Schaadt_TableS1.pdf.jpg
Schaadt_TableS1.pdf.jpg
Generated Thumbnail
image/jpeg
78237
https://repository.helmholtz-hzi.de/bitstream/10033/622191/11/Schaadt_TableS1.pdf.jpg
dbf0ccfe05d48cee91af2269cbc949a0
MD5
11
false
TEXT
Schaadt et al.pdf.txt
Schaadt et al.pdf.txt
Extracted text
text/plain
52680
https://repository.helmholtz-hzi.de/bitstream/10033/622191/6/Schaadt%20et%20al.pdf.txt
dddeea9e50a1c1052a643c9ed20fa795
MD5
6
false
Schaadt_appendix S1.pdf.txt
Schaadt_appendix S1.pdf.txt
Extracted text
text/plain
1153
https://repository.helmholtz-hzi.de/bitstream/10033/622191/7/Schaadt_appendix%20S1.pdf.txt
4a3c701ec6bce11fe84eb66aa46d399e
MD5
7
false
Schaadt_TableS1.pdf.txt
Schaadt_TableS1.pdf.txt
Extracted text
text/plain
1149
https://repository.helmholtz-hzi.de/bitstream/10033/622191/8/Schaadt_TableS1.pdf.txt
5979375947e07ca2e36515ec3f5b732b
MD5
8
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622191/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622191/4/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
4
false
ORIGINAL
Schaadt et al.pdf
Schaadt et al.pdf
Open Access publication
application/pdf
2972627
https://repository.helmholtz-hzi.de/bitstream/10033/622191/1/Schaadt%20et%20al.pdf
802a0129612a17bed184b4ed528172c8
MD5
1
true
Schaadt_appendix S1.pdf
Schaadt_appendix S1.pdf
appendix S1
application/pdf
61300
https://repository.helmholtz-hzi.de/bitstream/10033/622191/2/Schaadt_appendix%20S1.pdf
389b83523bd655931830fe1bf20bdbaa
MD5
2
false
Schaadt_TableS1.pdf
Schaadt_TableS1.pdf
Table S1
application/pdf
56734
https://repository.helmholtz-hzi.de/bitstream/10033/622191/3/Schaadt_TableS1.pdf
984cea5003638368a1accf604a1e60df
MD5
3
false
10033/622191
oai:repository.helmholtz-hzi.de:10033/622191
2020-04-07 05:15:09.27
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6221952020-03-11T02:09:44Zcom_10033_620659col_10033_620660
Alfonso, Juan Carlos L
f00ab4bd9d68430b9f0bdc92a4ed4c93
Papaxenopoulou, Lito A
35da953d3f344f9b0a816d8b287e395c
300
Mascheroni, Pietro
f046cc349bd1d2fe247ffdccdb2b8d21
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-03-10T13:31:56Z
2020-03-10T13:31:56Z
2020-02-11
iScience. 2020 Feb 11;23(3):100897. doi: 10.1016/j.isci.2020.100897.
2589-0042
32092699
10.1016/j.isci.2020.100897
http://hdl.handle.net/10033/622195
iScience
Emerging evidence demonstrates that radiotherapy induces immunogenic death on tumor cells that emit immunostimulating signals resulting in tumor-specific immune responses. However, the impact of tumor features and microenvironmental factors on the efficacy of radiation-induced immunity remains to be elucidated. Herein, we use a calibrated model of tumor-effector cell interactions to investigate the potential benefits and immunological consequences of radiotherapy. Simulations analysis suggests that radiotherapy success depends on the functional tumor vascularity extent and reveals that the pre-treatment tumor size is not a consistent determinant of treatment outcomes. The one-size-fits-all approach of conventionally fractionated radiotherapy is predicted to result in some overtreated patients. In addition, model simulations also suggest that an arbitrary increase in treatment duration does not necessarily result in better tumor control. This study highlights the potential benefits of tumor-immune ecosystem profiling during treatment planning to better harness the immunogenic potential of radiotherapy.
en
Elsevier/Cell Press
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Bioinformatics
Cancer
Mathematical Biosciences
On the Immunological Consequences of Conventionally Fractionated Radiotherapy.
Article
iScience
2020-03-10T13:31:57Z
THUMBNAIL
Alfonso et al.pdf.jpg
Alfonso et al.pdf.jpg
Generated Thumbnail
image/jpeg
80075
https://repository.helmholtz-hzi.de/bitstream/10033/622195/5/Alfonso%20et%20al.pdf.jpg
3c8ddf966af11276c3a5c504ea96f731
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
40019
https://repository.helmholtz-hzi.de/bitstream/10033/622195/6/elsevier-thumbnail.png
93641daf9d558f4de9b686539dc56dc1
MD5
6
false
TEXT
Alfonso et al.pdf.txt
Alfonso et al.pdf.txt
Extracted text
text/plain
84250
https://repository.helmholtz-hzi.de/bitstream/10033/622195/4/Alfonso%20et%20al.pdf.txt
15f1a3cffd3f659a1c7a301e57c09772
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622195/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622195/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Alfonso et al.pdf
Alfonso et al.pdf
Open Access publication
application/pdf
7580690
https://repository.helmholtz-hzi.de/bitstream/10033/622195/1/Alfonso%20et%20al.pdf
19a386552cb61e72f0180eea6f82d3a4
MD5
1
true
10033/622195
oai:repository.helmholtz-hzi.de:10033/622195
2020-03-11 02:09:44.189
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6222502020-05-11T01:28:08Zcom_10033_620659col_10033_620660
Goldberg, Amy
7b255b330ad605c23155a08d6dde4cfa
300
Rastogi, Ananya
01f1c39aa3ebf2ec475efcc729c8b3f3
300
Rosenberg, Noah A.
b2ca9300beb8628fd28f8c0cfcc81cc7
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2020-05-10T13:48:51Z
2020-05-10T13:48:51Z
2020-04-07
Theor Popul Biol. 2020 Apr 7. pii: S0040-5809(20)30025-3. doi: 10.1016/j.tpb.2020.02.004.
0040-5809
32275920
10.1016/j.tpb.2020.02.004
http://hdl.handle.net/10033/622250
Theoretical population Biology
S0040580920300253
Populations whose mating pairs have levels of similarity in phenotypes or genotypes that differ systematically from the level expected under random mating are described as experiencing assortative mating. Excess similarity in mating pairs is termed positive assortative mating, and excess dissimilarity is negative assortative mating. In humans, empirical studies suggest that mating pairs from various admixed populations-whose ancestry derives from two or more source populations-possess correlated ancestry components that indicate the occurrence of positive assortative mating on the basis of ancestry. Generalizing a two-sex mechanistic admixture model, we devise a model of one form of ancestry-assortative mating that occurs through preferential mating based on source population. Under the model, we study the moments of the admixture fraction distribution for different assumptions about mating preferences, including both positive and negative assortative mating by population. We demonstrate that whereas the mean admixture under assortative mating is equivalent to that of a corresponding randomly mating population, the variance of admixture depends on the level and direction of assortative mating. We consider two special cases of assortative mating by population: first, a single admixture event, and second, constant contributions to the admixed population over time In contrast to standard settings in which positive assortment increases variation within a population, certain assortative mating scenarios allow the variance of admixture to decrease relative to a corresponding randomly mating population: with the three populations we consider, the variance-increasing effect of positive assortative mating within a population might be overwhelmed by a variance-decreasing effect emerging from mating preferences involving other pairs of populations. The effect of assortative mating is smaller on the X chromosome than on the autosomes because inheritance of the X in males depends only on the mother's ancestry, not on the mating pair. Because the variance of admixture is informative about the timing of admixture and possibly about sex-biased admixture contributions, the effects of assortative mating are important to consider in inferring features of population history from distributions of admixture values. Our model provides a framework to quantitatively study assortative mating under flexible scenarios of admixture over time.
National Institutes of Health
en
Elsevier BV
Attribution-NonCommercial-ShareAlike 4.0 International
https://www.elsevier.com/tdm/userlicense/1.0/
http://creativecommons.org/licenses/by-nc-sa/4.0/
Ecology, Evolution, Behavior and Systematics
Assortative mating by population of origin in a mechanistic model of admixture
Article
Theoretical Population Biology
2020-05-10T13:48:53Z
THUMBNAIL
Goldberg, Rastogi and Rosernberg.pdf.jpg
Goldberg, Rastogi and Rosernberg.pdf.jpg
Generated Thumbnail
image/jpeg
87624
https://repository.helmholtz-hzi.de/bitstream/10033/622250/5/Goldberg%2c%20Rastogi%20and%20Rosernberg.pdf.jpg
933ea0b89a209e51b288a3299393e063
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
57034
https://repository.helmholtz-hzi.de/bitstream/10033/622250/6/elsevier-thumbnail.png
f1d4c54862ff5ee504e3a485db291e04
MD5
6
false
TEXT
Goldberg, Rastogi and Rosernberg.pdf.txt
Goldberg, Rastogi and Rosernberg.pdf.txt
Extracted text
text/plain
98958
https://repository.helmholtz-hzi.de/bitstream/10033/622250/4/Goldberg%2c%20Rastogi%20and%20Rosernberg.pdf.txt
74236b7b778ae7349394c7fef8146587
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622250/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622250/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Goldberg, Rastogi and Rosernberg.pdf
Goldberg, Rastogi and Rosernberg.pdf
bioRxiv preprint of an Open Access publication
application/pdf
2978877
https://repository.helmholtz-hzi.de/bitstream/10033/622250/1/Goldberg%2c%20Rastogi%20and%20Rosernberg.pdf
9a6d010e61a4454e7154cfc12e4ffd9e
MD5
1
true
10033/622250
oai:repository.helmholtz-hzi.de:10033/622250
2020-05-11 01:28:08.558
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6224332020-09-28T10:51:11Zcom_10033_128109com_10033_620659com_10033_6839com_10033_620618col_10033_128110col_10033_620660col_10033_621495col_10033_620621
Bonifacius, Agnes
7388ba497444e1c6681c1b0c117661cc
500
Goldmann, Oliver
c5128be52b1f8f05b1836584bc24fdc8
500
Floess, Stefan
5ffe089d50f6ea39d568657c60ebcc8f
500
Holtfreter, Silva
e6939ed41f0fdc0fec5c67098fe2414c
300
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Nordengrün, Maria
5f3c9a9e724346c2da3ffcb0097b555f
500
Kruse, Friederike
2c6700217ccb42b3737f61f9bb943e04
500
Lochner, Matthias
d5ad5574cc2e9452baaffad50d9ce3d9
500
Falk, Christine S
84fa0c3390a25e71bc272964dddb40ff
Schmitz, Ingo
33252c7e3ac40c72ff226b0ae1187c4b
500
Bröker, Barbara M
31b5a39a7d6dd670f81a598a3159c90e
500
Medina, Eva
ede6c0e74e71c9a362976424953beb0b
600
http://orcid.org/0000-0001-9073-0223
Huehn, Jochen
593aa066bacc8199a66ef7fe31379623
600
http://orcid.org/0000-0001-8071-1379
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-09-10T07:20:07Z
2020-09-10T07:20:07Z
2020-08-07
Front Immunol. 2020;11:1579. Published 2020 Aug 7. doi:10.3389/fimmu.2020.01579.
32849537
10.3389/fimmu.2020.01579
http://hdl.handle.net/10033/622433
1664-3224
Frontiers in immunology
Staphylococcus aureus can cause life-threatening diseases, and hospital- as well as community-associated antibiotic-resistant strains are an emerging global public health problem. Therefore, prophylactic vaccines or immune-based therapies are considered as alternative treatment opportunities. To develop such novel treatment approaches, a better understanding of the bacterial virulence and immune evasion mechanisms and their potential effects on immune-based therapies is essential. One important staphylococcal virulence factor is alpha-toxin, which is able to disrupt the epithelial barrier in order to establish infection. In addition, alpha-toxin has been reported to modulate other cell types including immune cells. Since CD4+ T cell-mediated immunity is required for protection against S. aureus infection, we were interested in the ability of alpha-toxin to directly modulate CD4+ T cells. To address this, murine naïve CD4+ T cells were differentiated in vitro into effector T cell subsets in the presence of alpha-toxin. Interestingly, alpha-toxin induced death of Th1-polarized cells, while cells polarized under Th17 conditions showed a high resistance toward increasing concentrations of this toxin. These effects could neither be explained by differential expression of the cellular alpha-toxin receptor ADAM10 nor by differential activation of caspases, but might result from an increased susceptibility of Th1 cells toward Ca2+-mediated activation-induced cell death. In accordance with the in vitro findings, an alpha-toxin-dependent decrease of Th1 and concomitant increase of Th17 cells was observed in vivo during S. aureus bacteremia. Interestingly, corresponding subsets of innate lymphoid cells and γδ T cells were similarly affected, suggesting a more general effect of alpha-toxin on the modulation of type 1 and type 3 immune responses. In conclusion, we have identified a novel alpha-toxin-dependent immunomodulatory strategy of S. aureus, which can directly act on CD4+ T cells and might be exploited for the development of novel immune-based therapeutic approaches to treat infections with antibiotic-resistant S. aureus strains.
en
Frontiers
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
CD4+ T cells
Staphylococcus aureus
alpha-toxin
innate lymphoid cells
γδ T cells
Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses.
Article
11
1579
Frontiers in immunology
Switzerland
2020-09-10T07:20:07Z
THUMBNAIL
Bonifacius et al.pdf.jpg
Bonifacius et al.pdf.jpg
Generated Thumbnail
image/jpeg
125753
https://repository.helmholtz-hzi.de/bitstream/10033/622433/5/Bonifacius%20et%20al.pdf.jpg
fad8c15c8c1f6fd70ea9ea029cad9686
MD5
5
false
TEXT
Bonifacius et al.pdf.txt
Bonifacius et al.pdf.txt
Extracted text
text/plain
66618
https://repository.helmholtz-hzi.de/bitstream/10033/622433/4/Bonifacius%20et%20al.pdf.txt
7846f5c3b984215062f4485637ea2ae1
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622433/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622433/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Bonifacius et al.pdf
Bonifacius et al.pdf
Open Access publication
application/pdf
1213913
https://repository.helmholtz-hzi.de/bitstream/10033/622433/1/Bonifacius%20et%20al.pdf
2adecdd8b351f0bc06d4350bc05c7992
MD5
1
true
10033/622433
oai:repository.helmholtz-hzi.de:10033/622433
2020-09-28 10:51:11.932
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6224992020-10-09T01:33:40Zcom_10033_620659col_10033_620660
Siokis, Anastasios
a874c68d3386019489682d501c19027a
500
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-10-08T09:03:05Z
2020-10-08T09:03:05Z
2020-09-04
. Int J Mol Sci. 2020 Sep 4;21(18):E6473. doi: 10.3390/ijms21186473.
32899840
10.3390/ijms21186473
http://hdl.handle.net/10033/622499
1422-0067
International journal of molecular sciences
Immunological synapse (IS) formation is a key event during antigen recognition by T cells. Recent experimental evidence suggests that the affinity between T cell receptors (TCRs) and antigen is actively modulated during the early steps of TCR signaling. In this work, we used an agent-based model to study possible mechanisms for affinity modulation during IS formation. We show that, without any specific active mechanism, the observed affinity between receptors and ligands evolves over time and depends on the density of ligands of the antigen peptide presented by major histocompatibility complexes (pMHC) and TCR molecules. A comparison between the presence or absence of TCR-pMHC centrally directed flow due to F-actin coupling suggests that centripetal transport is a potential mechanism for affinity modulation. The model further suggests that the time point of affinity measurement during immune synapse formation is critical. Finally, a mathematical model of F-actin foci formation incorporated in the agent-based model shows that TCR affinity can potentially be actively modulated by positive/negative feedback of the F-actin foci on the TCR-pMHC association rate kon.
en
MDPI
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
F-actin foci
TCR cooperativity
agent-based modeling
immunological synapse
Agent-Based Modeling of T Cell Receptor Cooperativity.
Article
21
18
International journal of molecular sciences
Switzerland
2020-10-08T09:03:06Z
THUMBNAIL
Siokis, Robert and Meyer-Hermann.pdf.jpg
Siokis, Robert and Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
89469
https://repository.helmholtz-hzi.de/bitstream/10033/622499/5/Siokis%2c%20Robert%20and%20Meyer-Hermann.pdf.jpg
4e2e80f81f40ea2b6d32c8522fe185cf
MD5
5
false
TEXT
Siokis, Robert and Meyer-Hermann.pdf.txt
Siokis, Robert and Meyer-Hermann.pdf.txt
Extracted text
text/plain
53433
https://repository.helmholtz-hzi.de/bitstream/10033/622499/4/Siokis%2c%20Robert%20and%20Meyer-Hermann.pdf.txt
3901257ec1cd63e1c19e2217473d628a
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622499/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622499/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Siokis, Robert and Meyer-Hermann.pdf
Siokis, Robert and Meyer-Hermann.pdf
Open Access publication
application/pdf
2359173
https://repository.helmholtz-hzi.de/bitstream/10033/622499/1/Siokis%2c%20Robert%20and%20Meyer-Hermann.pdf
ab6d5f95a1d97e2e6a7a9ab1c6c5a390
MD5
1
true
10033/622499
oai:repository.helmholtz-hzi.de:10033/622499
2020-10-09 01:33:40.903
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6225272020-10-30T01:35:47Zcom_10033_620659com_10033_311308col_10033_620721col_10033_620660
Theobald, Sebastian J
b20691f6a8eaced112a6952abc279f6f
500
Kreer, Christoph
2d526a11b1bb566e1a0ad6001fb549ee
300
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Bonifacius, Agnes
7388ba497444e1c6681c1b0c117661cc
500
Eiz-Vesper, Britta
3170523f1490c5988c8616dcbb214477
500
Figueiredo, Constanca
9a7a1b9898006185f224072e816a4c9b
500
Mach, Michael
f1a94e23d197d07777b6f2ae76abfadd
500
Backovic, Marija
d90be043bb0268027fb953a7af684729
300
Ballmaier, Matthias
7abbdef38bc018b44609c0ddb37328c7
300
Koenig, Johannes
0790dd9eae41fa038b218eaa105c064b
300
Olbrich, Henning
6419f9e0e6535dff36a34f3097094543
500
Schneider, Andreas
e0f0eceff50ffc02b2f2f318141b786f
500
Volk, Valery
471270676314f896c59426533c0b8380
500
Danisch, Simon
e414529cf27089a2211c9eadfe2cff3e
500
Gieselmann, Lutz
941ff2aeee5abc0bd0c5136cc6bb6125
300
Ercanoglu, Meryem Seda
51377fcdb9b9d21bfcde34612b0ba5ce
300
Messerle, Martin
f32ed852de2e0307d35955c90176a6c1
500
Kaisenberg, Constantin von
3426e20133066377d83af4ca75d5483f
Witte, Torsten
c0736c79eb5dfbe26a046ab10e01bd10
500
Klawonn, Frank
da2644d10297b6bb437e1cce18952393
600
http://orcid.org/0000-0001-9613-182X
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Klein, Florian
19d7a7315874b4bd00f298adcc37fde1
500
Stripecke, Renata
2a542d77371b05057a72e0d5889405a2
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-10-22T09:33:34Z
2020-10-22T09:33:34Z
2020-07-15
PLoS Pathog. 2020 Jul 15;16(7):e1008560. doi: 10.1371/journal.ppat.1008560.
32667948
10.1371/journal.ppat.1008560
http://hdl.handle.net/10033/622527
1553-7374
PLoS pathogens
Human cytomegalovirus (HCMV) causes serious complications to immune compromised hosts. Dendritic cells (iDCgB) expressing granulocyte-macrophage colony-stimulating factor, interferon-alpha and HCMV-gB were developed to promote de novo antiviral adaptive responses. Mice reconstituted with a human immune system (HIS) were immunized with iDCgB and challenged with HCMV, resulting into 93% protection. Immunization stimulated the expansion of functional effector memory CD8+ and CD4+ T cells recognizing gB. Machine learning analyses confirmed bone marrow T/CD4+, liver B/IgA+ and spleen B/IgG+ cells as predictive biomarkers of immunization (≈87% accuracy). CD8+ and CD4+ T cell responses against gB were validated. Splenic gB-binding IgM-/IgG+ B cells were sorted and analyzed at a single cell level. iDCgB immunizations elicited human-like IgG responses with a broad usage of various IgG heavy chain V gene segments harboring variable levels of somatic hypermutation. From this search, two gB-binding human monoclonal IgGs were generated that neutralized HCMV infection in vitro. Passive immunization with these antibodies provided proof-of-concept evidence of protection against HCMV infection. This HIS/HCMV in vivo model system supported the validation of novel active and passive immune therapies for future clinical translation.
en
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV.
Article
16
7
e1008560
PLoS pathogens
United States
2020-10-22T09:33:37Z
THUMBNAIL
Theobald_supp.tif.jpg
Theobald_supp.tif.jpg
IM Thumbnail
image/jpeg
80319
https://repository.helmholtz-hzi.de/bitstream/10033/622527/6/Theobald_supp.tif.jpg
1bbc9d61bf6c617b054d93664eda4b96
MD5
6
false
Theobald et al.pdf.jpg
Theobald et al.pdf.jpg
Generated Thumbnail
image/jpeg
117228
https://repository.helmholtz-hzi.de/bitstream/10033/622527/7/Theobald%20et%20al.pdf.jpg
75bf8cceaff8fac4c1defe6a280c16dc
MD5
7
false
TEXT
Theobald et al.pdf.txt
Theobald et al.pdf.txt
Extracted text
text/plain
126512
https://repository.helmholtz-hzi.de/bitstream/10033/622527/5/Theobald%20et%20al.pdf.txt
94705834e7ccd4868e5783c400e7c6ad
MD5
5
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622527/4/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
4
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622527/3/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
3
false
ORIGINAL
Theobald et al.pdf
Theobald et al.pdf
Open Access publication
application/pdf
4417971
https://repository.helmholtz-hzi.de/bitstream/10033/622527/1/Theobald%20et%20al.pdf
6b17efa3eb0cef9b6068770bf6ff8609
MD5
1
true
Theobald_supp.tif
Theobald_supp.tif
supplemental figure 1
image/tiff
2203096
https://repository.helmholtz-hzi.de/bitstream/10033/622527/2/Theobald_supp.tif
6ca05b1d98b1d4ab744d39d794d67f4d
MD5
2
false
10033/622527
oai:repository.helmholtz-hzi.de:10033/622527
2020-10-30 01:35:47.218
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6225332020-11-04T04:36:58Zcom_10033_620659col_10033_620660
Rizzuti, Ilaria Francesca
b317e0bcc386536e79aad9432990f934
300
Mascheroni, Pietro
f046cc349bd1d2fe247ffdccdb2b8d21
500
Arcucci, Silvia
cdb22e024005fce3a1d0b9ff58065c1b
300
Ben-Mériem, Zacchari
b649a0c6fbb64435825229393666fe95
300
Prunet, Audrey
b328a0243abecd2e13cef1f2571d0afc
300
Barentin, Catherine
33b40560b79ffe3cfe92432302d7ce42
300
Rivière, Charlotte
0c3e90004480ea90daf4e22fdd2f669d
300
Delanoë-Ayari, Hélène
79ed4d2b95d710db918acf2506a0e068
300
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Guillermet-Guibert, Julie
a71c81bd686d5324782cacc8bd796deb
300
Delarue, Morgan
e7bf3a04dfcf57471368592e1ffddaf2
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-10-26T10:20:54Z
2020-10-26T10:20:54Z
2020-09-18
Phys Rev Lett. 2020 Sep 18;125(12):128103. doi: 10.1103/PhysRevLett.125.128103.
33016731
10.1103/PhysRevLett.125.128103
http://hdl.handle.net/10033/622533
1079-7114
Physical review letters
While many cellular mechanisms leading to chemotherapeutic resistance have been identified, there is an increasing realization that tumor-stroma interactions also play an important role. In particular, mechanical alterations are inherent to solid cancer progression and profoundly impact cell physiology. Here, we explore the influence of compressive stress on the efficacy of chemotherapeutics in pancreatic cancer spheroids. We find that increased compressive stress leads to decreased drug efficacy. Theoretical modeling and experiments suggest that mechanical stress decreases cell proliferation which in turn reduces the efficacy of chemotherapeutics that target proliferating cells. Our work highlights a mechanical form of drug resistance and suggests new strategies for therapy.
en
American Physical Society
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Mechanical Control of Cell Proliferation Increases Resistance to Chemotherapeutic Agents.
Article
125
12
128103
Physical review letters
United States
2020-10-26T10:20:55Z
THUMBNAIL
Rizzuti et al.pdf.jpg
Rizzuti et al.pdf.jpg
Generated Thumbnail
image/jpeg
48718
https://repository.helmholtz-hzi.de/bitstream/10033/622533/5/Rizzuti%20et%20al.pdf.jpg
b161b88163fc58f406f007356be11d7f
MD5
5
false
TEXT
Rizzuti et al.pdf.txt
Rizzuti et al.pdf.txt
Extracted text
text/plain
33009
https://repository.helmholtz-hzi.de/bitstream/10033/622533/4/Rizzuti%20et%20al.pdf.txt
94bcb88f0f66f4a84cec38e4de426b63
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622533/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622533/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Rizzuti et al.pdf
Rizzuti et al.pdf
Open Access publication
application/pdf
3315331
https://repository.helmholtz-hzi.de/bitstream/10033/622533/1/Rizzuti%20et%20al.pdf
b8b259ba04fcc60547bea66894f999c5
MD5
1
true
10033/622533
oai:repository.helmholtz-hzi.de:10033/622533
2020-11-04 04:36:58.627
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226012020-11-20T01:46:27Zcom_10033_620659col_10033_620660
Reimer, Dorothea
d1460c6e95b21389f154f22413587873
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Rakhymzhan, Asylkhan
e41b7ad6ec35a61668e627e971ad458e
300
Steinmetz, Tobit
971256b575e082d9d36c378146840682
500
Tripal, Philipp
2398b12641ca7b126d5b0b38a30878f7
300
Thomas, Jana
828013ca2e022eea489587cce83fcfa2
300
Boettcher, Martin
3413c5470f0057c9f3fcfc16c33a8074
300
Mougiakakos, Dimitrios
2cc1a7dce8a4a35b7b8dd35b3aed23c7
500
Schulz, Sebastian R
375c81de90b536eef9536bc2845c51a7
500
Urbanczyk, Sophia
6b6f9135e4981c0e162c8ac516b2017c
500
Hauser, Anja E
eeffcec553dcaabdd8c2665c97bc72a5
500
Niesner, Raluca A
2d58d499424de28d7b15858a50a2ec91
300
Mielenz, Dirk
dabb018229252813207a6a33451969c4
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-11-19T15:12:26Z
2020-11-19T15:12:26Z
2020-08-11
Cell Rep. 2020 Aug 11;32(6):108030. doi: 10.1016/j.celrep.2020.108030.
32783949
10.1016/j.celrep.2020.108030
http://hdl.handle.net/10033/622601
2211-1247
Cell reports
Plasma cells secreting affinity-matured antibodies develop in germinal centers (GCs), where B cells migrate persistently and directionally over defined periods of time. How modes of GC B cell migration influence plasma cell development remained unclear. Through genetic deletion of the F-actin bundling protein Swiprosin-1/EF-hand domain family member 2 (EFhd2) and by two-photon microscopy, we show that EFhd2 restrains B cell speed in GCs and hapten-specific plasma cell output. Modeling the GC reaction reveals that increasing GC B cell speed promotes plasma cell generation. Lack of EFhd2 also reduces contacts of GC B cells with follicular dendritic cells in vivo. Computational modeling uncovers that both GC output and antibody affinity depend quantitatively on contacts of GC B cells with follicular dendritic cells when B cells migrate more persistently. Collectively, our data explain how GC B cells integrate speed and persistence of cell migration with B cell receptor affinity.
en
Elsevier (CellPress)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
B cell receptor
Swiprosin-1/EFhd2
actin cytoskeleton
differentiation
follicular dendritic cell
germinal center
migration
plasma cell
selection
synapse
B Cell Speed and B-FDC Contacts in Germinal Centers Determine Plasma Cell Output via Swiprosin-1/EFhd2.
Article
32
6
108030
Cell reports
United States
2020-11-19T15:12:27Z
THUMBNAIL
Reimer et al.pdf.jpg
Reimer et al.pdf.jpg
Generated Thumbnail
image/jpeg
84188
https://repository.helmholtz-hzi.de/bitstream/10033/622601/5/Reimer%20et%20al.pdf.jpg
4c4888101f36624148f9e3c2b3558710
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
44793
https://repository.helmholtz-hzi.de/bitstream/10033/622601/6/elsevier-thumbnail.png
7fe27d4d64533acbf861919f572c3698
MD5
6
false
TEXT
Reimer et al.pdf.txt
Reimer et al.pdf.txt
Extracted text
text/plain
79476
https://repository.helmholtz-hzi.de/bitstream/10033/622601/4/Reimer%20et%20al.pdf.txt
e3a5f77f2abc45053f2442986402f306
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622601/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622601/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Reimer et al.pdf
Reimer et al.pdf
Open Access article
application/pdf
4909555
https://repository.helmholtz-hzi.de/bitstream/10033/622601/1/Reimer%20et%20al.pdf
0f3b7ccd5d7f655ddfe6e3c499bd55e1
MD5
1
true
10033/622601
oai:repository.helmholtz-hzi.de:10033/622601
2020-11-20 01:46:27.118
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226022020-11-20T01:46:27Zcom_10033_620659col_10033_620660
Hoore, Masoud
f6650a90c142adfccf8976ed0961d7a5
300
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Montaseri, Ghazal
0188311a96861e58b03f0dde1e12040f
500
Mitra, Tanmay
956bf08ca9fa09db5ec611d4ea747195
300
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-11-19T15:23:56Z
2020-11-19T15:23:56Z
2020-07-22
Biophys J. 2020 Aug 18;119(4):862-872. doi: 10.1016/j.bpj.2020.07.011. Epub 2020 Jul 22.
32758420
10.1016/j.bpj.2020.07.011
http://hdl.handle.net/10033/622602
1542-0086
Biophysical journal
Deposition of amyloid-β (Aβ) fibers in the extracellular matrix of the brain is a ubiquitous feature associated with several neurodegenerative disorders, especially Alzheimer's disease (AD). Although many of the biological aspects that contribute to the formation of Aβ plaques are well addressed at the intra- and intercellular levels in short timescales, an understanding of how Aβ fibrillization usually starts to dominate at a longer timescale despite the presence of mechanisms dedicated to Aβ clearance is still lacking. Furthermore, no existing mathematical model integrates the impact of diurnal neural activity as emanated from circadian regulation to predict disease progression due to a disruption in the sleep-wake cycle. In this study, we develop a minimal model of Aβ fibrillization to investigate the onset of AD over a long timescale. Our results suggest that the diseased state is a manifestation of a phase change of the system from soluble Aβ (sAβ) to fibrillar Aβ (fAβ) domination upon surpassing a threshold in the production rate of sAβ. By incorporating the circadian rhythm into our model, we reveal that fAβ accumulation is crucially dependent on the regulation of the sleep-wake cycle, thereby indicating the importance of good sleep hygiene in averting AD onset. We also discuss potential intervention schemes to reduce fAβ accumulation in the brain by modification of the critical sAβ production rate.
en
Elsevier (CellPress)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Mathematical Model Shows How Sleep May Affect Amyloid-β Fibrillization.
Article
119
4
862
872
Biophysical journal
United States
2020-11-19T15:23:57Z
THUMBNAIL
Hoore et al.pdf.jpg
Hoore et al.pdf.jpg
Generated Thumbnail
image/jpeg
113724
https://repository.helmholtz-hzi.de/bitstream/10033/622602/5/Hoore%20et%20al.pdf.jpg
2957758ceae3b2f48fb5343466f23760
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
95414
https://repository.helmholtz-hzi.de/bitstream/10033/622602/6/elsevier-thumbnail.png
337e5dd11c623435ae4649af2b39ea3f
MD5
6
false
TEXT
Hoore et al.pdf.txt
Hoore et al.pdf.txt
Extracted text
text/plain
56657
https://repository.helmholtz-hzi.de/bitstream/10033/622602/4/Hoore%20et%20al.pdf.txt
83f55a6e5f0d0910049f2f7f248cadf8
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622602/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622602/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Hoore et al.pdf
Hoore et al.pdf
Open Access article
application/pdf
1388575
https://repository.helmholtz-hzi.de/bitstream/10033/622602/1/Hoore%20et%20al.pdf
e6d332179b0dc5d17b50d9a4e55c7aaf
MD5
1
true
10033/622602
oai:repository.helmholtz-hzi.de:10033/622602
2020-11-20 01:46:27.171
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226102020-12-03T01:45:45Zcom_10033_620659col_10033_620660
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Montaseri, Ghazal
0188311a96861e58b03f0dde1e12040f
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-11-25T10:28:57Z
2020-11-25T10:28:57Z
2020-10-12
iScience. 2020 Oct 12;23(11):101663. doi: 10.1016/j.isci.2020.101663.
33134893
10.1016/j.isci.2020.101663
http://hdl.handle.net/10033/622610
2589-0042
iScience
Regulatory T cells (Treg) are suppressor cells that control self-reactive and excessive effector conventional T helper cell (Tconv) responses. Breakdown of the balance between Tregs and Tconvs is a hallmark of autoimmune and inflammatory diseases. Interleukin-2 (IL-2) is a growth factor for both populations and subtle leverage to restore the healthy immune balance in IL-2 therapy. By using a mechanistic mathematical model, we introduced an adaptive control strategy to design the minimal therapeutic IL-2 dosage required to increase and stabilize Treg population and restrict inflammatory response. This adaptive protocol allows for dose adjustments based on the feedback of the immune kinetics of the patient. Our simulation results showed that a minimal Treg population was required to restrict the transient side effect of IL-2 injections on the effector Tconv response. In silico results suggested that a combination of IL-2 and adoptive Treg transfer therapies can limit this side effect.
en
Elsevier (Cell Press)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Biological Sciences
Immunology
Mathematical Bioscience
An Adaptive Control Scheme for Interleukin-2 Therapy.
Article
23
11
101663
iScience
United States
2020-11-25T10:28:58Z
THUMBNAIL
elsevier-thumbnail.png
application/octet-stream
42142
https://repository.helmholtz-hzi.de/bitstream/10033/622610/5/elsevier-thumbnail.png
8c697ff4f84c1696eff05d74a91b4ec1
MD5
5
false
Khailaie, Montaseri.,and Meyer-Hermann.pdf.jpg
Khailaie, Montaseri.,and Meyer-Hermann.pdf.jpg
Generated Thumbnail
image/jpeg
79223
https://repository.helmholtz-hzi.de/bitstream/10033/622610/6/Khailaie%2c%20Montaseri.%2cand%20Meyer-Hermann.pdf.jpg
e9b5a82962f6d22cf18631571d5f5955
MD5
6
false
TEXT
Khailaie, Montaseri.,and Meyer-Hermann.pdf.txt
Khailaie, Montaseri.,and Meyer-Hermann.pdf.txt
Extracted text
text/plain
51423
https://repository.helmholtz-hzi.de/bitstream/10033/622610/4/Khailaie%2c%20Montaseri.%2cand%20Meyer-Hermann.pdf.txt
d0ec4638a5b5ead5e44bc7ec5440f74e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622610/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622610/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Khailaie, Montaseri.,and Meyer-Hermann.pdf
Khailaie, Montaseri.,and Meyer-Hermann.pdf
Open Access article
application/pdf
2514247
https://repository.helmholtz-hzi.de/bitstream/10033/622610/1/Khailaie%2c%20Montaseri.%2cand%20Meyer-Hermann.pdf
8d5a018e6b124b0b690daf605c1e837f
MD5
1
true
10033/622610
oai:repository.helmholtz-hzi.de:10033/622610
2020-12-03 01:45:45.47
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226122020-12-03T01:44:26Zcom_10033_620659col_10033_620660
Xenos, Michalis A.
3bbdaedddd8358ed0a2b9a89b2a4d69a
300
Petropoulou, Eugenia N.
5f63309a58995ca78adf6abda81a16ed
300
Siokis, Anastasios
a874c68d3386019489682d501c19027a
500
Mahabaleshwar, U. S.
d519b8d5ca6b418dacb251a4b0036e45
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-11-25T13:37:46Z
2020-11-25T13:37:46Z
2020-05-01
Symmetry 2020, 12, 710.
10.3390/SYM12050710
http://hdl.handle.net/10033/622612
20738994
Symmetry
2-s2.0-85085360972
SCOPUS_ID:85085360972
The physical problem under consideration is the boundary layer problem of an incompressible, laminar flow, taking place over a flat plate in the presence of a pressure gradient and radiation. For the mathematical formulation of the problem, the partial differential equations of continuity, energy, and momentum are taken into consideration with the boundary layer simplifications. Using the dimensionless Falkner–Skan transformation, a nonlinear, nonhomogeneous, coupled system of partial differential equations (PDEs) is obtained, which is solved via the homotopy analysis method. The obtained analytical solution describes radiation and pressure gradient effects on the boundary layer flow. These analytical results reveal that the adverse or favorable pressure gradient influences the dimensionless velocity and the dimensionless temperature of the boundary layer. An adverse pressure gradient causes significant changes on the dimensionless wall shear parameter and the dimensionless wall heat-transfer parameter. Thermal radiation influences the thermal boundary layer. The analytical results are in very good agreement with the corresponding numerical ones obtained using a modification of the Keller’s-box method.
University of Salford Manchester
en
MDPI
info:eu-repo/grantAgreement/EC/H2020/757913
openAccess
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Approximate solution
Boundary layer
Homotopy analysis method
Pressure gradient
Thermal radiation
Solving the nonlinear boundary layer flow equations with pressure gradient and radiation
Article
12
5
Symmetry
2020-11-25T13:37:47Z
THUMBNAIL
Xenos et al.pdf.jpg
Xenos et al.pdf.jpg
Generated Thumbnail
image/jpeg
86829
https://repository.helmholtz-hzi.de/bitstream/10033/622612/5/Xenos%20et%20al.pdf.jpg
4a2ffbfcb9185bda57fe32fd9ac10791
MD5
5
false
TEXT
Xenos et al.pdf.txt
Xenos et al.pdf.txt
Extracted text
text/plain
49140
https://repository.helmholtz-hzi.de/bitstream/10033/622612/4/Xenos%20et%20al.pdf.txt
6242cf2d2ffd411243e992d6e7c8efa6
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622612/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622612/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Xenos et al.pdf
Xenos et al.pdf
Open Access publication
application/pdf
1001092
https://repository.helmholtz-hzi.de/bitstream/10033/622612/1/Xenos%20et%20al.pdf
470de89c93aacaae948f68a133fce34d
MD5
1
true
10033/622612
oai:repository.helmholtz-hzi.de:10033/622612
2020-12-03 01:44:26.324
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226252020-12-02T01:41:37Zcom_10033_620659col_10033_620660
Riebisch, Anna Katharina
11161db86dad392d23f31d40e501ba8a
300
Mühlen, Sabrina
4e8b34db292a312bfbda8769cd1a2740
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2020-12-01T10:08:25Z
2020-12-01T10:08:25Z
2020-07-27
Future Microbiol. 2020 Jul;15:945-958. doi: 10.2217/fmb-2019-0274. Epub 2020 Jul 27.
32716209
10.2217/fmb-2019-0274
http://hdl.handle.net/10033/622625
1746-0921
Future microbiology
The innate immune response resembles an essential barrier to bacterial infection. Many bacterial pathogens have, therefore, evolved mechanisms to evade from or subvert the host immune response in order to colonize, survive and multiply. The attaching and effacing pathogens enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Escherichia albertii and Citrobacter rodentium are Gram-negative extracellular gastrointestinal pathogens. They use a type III secretion system to inject effector proteins into the host cell to manipulate a variety of cellular processes. Over the last decade, considerable progress was made in identifying and characterizing the effector proteins of attaching and effacing pathogens that are involved in the inhibition of innate immune signaling pathways, in determining their host cell targets and elucidating the mechanisms they employ. Their functions will be reviewed here.
en
Future Medicine Ltd.
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
AE pathogens
apoptosis
inflammasome
inflammatory response
innate immune response
necroptosis
Attaching and effacing pathogens: the effector ABC of immune subversion.
Review
15
945
958
Future microbiology
England
2020-12-01T10:08:25Z
THUMBNAIL
Riebisch et al.pdf.jpg
Riebisch et al.pdf.jpg
Generated Thumbnail
image/jpeg
72291
https://repository.helmholtz-hzi.de/bitstream/10033/622625/9/Riebisch%20et%20al.pdf.jpg
c47adec1ddb3c0ec6d03c71997ef0638
MD5
9
false
Figure1_Inflammation.jpeg.jpg
Figure1_Inflammation.jpeg.jpg
Generated Thumbnail
image/jpeg
17060
https://repository.helmholtz-hzi.de/bitstream/10033/622625/10/Figure1_Inflammation.jpeg.jpg
6bc4d8a8c3046437f03bd0a308f53cbb
MD5
10
false
Figure2_Inflammasome.jpeg.jpg
Figure2_Inflammasome.jpeg.jpg
Generated Thumbnail
image/jpeg
12027
https://repository.helmholtz-hzi.de/bitstream/10033/622625/11/Figure2_Inflammasome.jpeg.jpg
e46c4e894dcf2cccd5e4e4b6c16d0a1b
MD5
11
false
Figure3_Cell_Death.jpeg.jpg
Figure3_Cell_Death.jpeg.jpg
Generated Thumbnail
image/jpeg
17002
https://repository.helmholtz-hzi.de/bitstream/10033/622625/12/Figure3_Cell_Death.jpeg.jpg
1d46b6d54d1f25bb13f4a1701a3fa2fd
MD5
12
false
Table1_Effector_functions.pdf.jpg
Table1_Effector_functions.pdf.jpg
Generated Thumbnail
image/jpeg
48308
https://repository.helmholtz-hzi.de/bitstream/10033/622625/14/Table1_Effector_functions.pdf.jpg
2e7ab198a0b41931f81ff34af639e8c5
MD5
14
false
TEXT
Riebisch et al.pdf.txt
Riebisch et al.pdf.txt
Extracted text
text/plain
53381
https://repository.helmholtz-hzi.de/bitstream/10033/622625/8/Riebisch%20et%20al.pdf.txt
2e0df57385651dd9c83ed75246886200
MD5
8
false
Table1_Effector_functions.pdf.txt
Table1_Effector_functions.pdf.txt
Extracted text
text/plain
8261
https://repository.helmholtz-hzi.de/bitstream/10033/622625/13/Table1_Effector_functions.pdf.txt
36f825aa25d8825ad247d8ab243698a6
MD5
13
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622625/7/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
7
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622625/6/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
6
false
ORIGINAL
Riebisch et al.pdf
Riebisch et al.pdf
submitted manuscript
application/pdf
370003
https://repository.helmholtz-hzi.de/bitstream/10033/622625/1/Riebisch%20et%20al.pdf
3c8038a383673f8fdc981b819039774b
MD5
1
true
Figure1_Inflammation.jpeg
Figure1_Inflammation.jpeg
figure 1
image/jpeg
1126072
https://repository.helmholtz-hzi.de/bitstream/10033/622625/2/Figure1_Inflammation.jpeg
d2dc1e176e81cceb56f499b4d69f4653
MD5
2
false
Figure2_Inflammasome.jpeg
Figure2_Inflammasome.jpeg
figure 2
image/jpeg
675827
https://repository.helmholtz-hzi.de/bitstream/10033/622625/3/Figure2_Inflammasome.jpeg
282b87a877ace8f86dfacc536817cec6
MD5
3
false
Figure3_Cell_Death.jpeg
Figure3_Cell_Death.jpeg
figure 3
image/jpeg
1172444
https://repository.helmholtz-hzi.de/bitstream/10033/622625/4/Figure3_Cell_Death.jpeg
dedcc68d8324ecbc91126a3fe3f22892
MD5
4
false
Table1_Effector_functions.pdf
Table1_Effector_functions.pdf
Table 1
application/pdf
179068
https://repository.helmholtz-hzi.de/bitstream/10033/622625/5/Table1_Effector_functions.pdf
8f4ef41d1171f8e508f88c7ed2020e4a
MD5
5
false
10033/622625
oai:repository.helmholtz-hzi.de:10033/622625
2020-12-02 01:41:37.693
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226662021-01-08T15:56:37Zcom_10033_620659col_10033_620660
Pae, Juhee
01b3ec2c2c9e84e030ccb849fbbf2a66
300
Ersching, Jonatan
0e9afe216cf324d5230a82fce03fb7ea
300
Castro, Tiago B R
ad677c3f280f2d183876c44864e7290d
300
Schips, Marta
74cbcb8b7d11f133b755b8597dd2f438
300
Mesin, Luka
1c119fe8cd293f8150f01ecb915d84ff
500
Allon, Samuel J
2d5c9e1191fee19e86d98754c17a6f6c
300
Ordovas-Montanes, Jose
41e02f91ca76693d01e5c9ae23607f87
300
Mlynarczyk, Coraline
19f94aa3fd578b070182c7b824f5d29e
300
Melnick, Ari
a1ebec9ec2bae6da466a92e8d7ce2641
300
Efeyan, Alejo
2bd901aaaa6a8beb07cc62bf721eea19
300
Shalek, Alex K
e36e8e3c20b4e9755d3704b14065abb5
300
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Victora, Gabriel D
f5d6a01775ef0b0c513db3746e04ee8d
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-01-07T11:00:27Z
2021-01-07T11:00:27Z
2021-04-01
The Journal of Experimental Medicine. 2021 Apr;218(4). DOI: 10.1084/jem.20201699.
33332554
10.1084/jem.20201699
http://hdl.handle.net/10033/622666
1540-9538
The Journal of experimental medicine
During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) and affinity-dependent selection in the light zone (LZ). This anatomical segregation imposes that the vigorous proliferation that allows clonal expansion of positively selected GC B cells takes place ostensibly in the absence of the signals that triggered selection in the LZ, as if by "inertia." We find that such inertial cycles specifically require the cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls the extent to which B cells proliferate in the DZ and is essential for effective clonal expansion of GC B cells in response to strong T follicular helper (Tfh) cell help. Introduction into the Ccnd3 gene of a Burkitt lymphoma-associated gain-of-function mutation (T283A) leads to larger GCs with increased DZ proliferation and, in older mice, clonal B cell lymphoproliferation, suggesting that the DZ inertial cell cycle program can be coopted by B cells undergoing malignant transformation.
en
Rockefeller University Press
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
©2021 Pae et al. Originally published in he Journal of Experimental Medicine. https://doi.org/10.1084/jem.20201699
Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells.
Article
218
4
The Journal of experimental medicine
United States
2021-01-07T11:00:28Z
THUMBNAIL
Pae et al.pdf.jpg
Pae et al.pdf.jpg
Generated Thumbnail
image/jpeg
125155
https://repository.helmholtz-hzi.de/bitstream/10033/622666/5/Pae%20et%20al.pdf.jpg
ff9277083245f7278d48ab40298ef5b6
MD5
5
false
TEXT
Pae et al.pdf.txt
Pae et al.pdf.txt
Extracted text
text/plain
96590
https://repository.helmholtz-hzi.de/bitstream/10033/622666/4/Pae%20et%20al.pdf.txt
587241296f717d346344a91f1e816d41
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622666/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622666/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Pae et al.pdf
Pae et al.pdf
allowed publisher's PDF
application/pdf
8335839
https://repository.helmholtz-hzi.de/bitstream/10033/622666/1/Pae%20et%20al.pdf
6bf7153fc3a82db665417969d3fb312d
MD5
1
true
10033/622666
oai:repository.helmholtz-hzi.de:10033/622666
2021-01-08 15:56:37.373
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6226802021-01-15T01:54:29Zcom_10033_620659col_10033_620660
Barua, Arnab
e5233ccc288d2dd0de9728c41dcbaf04
500
Nava-Sedeño, Josue M
6286660bbb254029a112e8958479b758
300
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-01-14T12:59:00Z
2021-01-14T12:59:00Z
2020-12-22
Sci Rep. 2020 Dec 22;10(1):22371. doi: 10.1038/s41598-020-79119-y.
33353977
10.1038/s41598-020-79119-y
http://hdl.handle.net/10033/622680
2045-2322
Scientific reports
Collective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that may serve as a generative model of collective migration without precise incorporation of full mechanistic details. Using statistical physics tools, we show that the famous Vicsek model is a special case of LEUP. Finally, to test the biological applicability of our theory, we apply LEUP to construct a model of the collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.
en
Nature research
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms.
Article
10
1
22371
Scientific reports
England
2021-01-14T12:59:01Z
THUMBNAIL
Barua et al.pdf.jpg
Barua et al.pdf.jpg
Generated Thumbnail
image/jpeg
111263
https://repository.helmholtz-hzi.de/bitstream/10033/622680/5/Barua%20et%20al.pdf.jpg
f0057779cbb759cc14c08b0e899d2cff
MD5
5
false
TEXT
Barua et al.pdf.txt
Barua et al.pdf.txt
Extracted text
text/plain
57686
https://repository.helmholtz-hzi.de/bitstream/10033/622680/4/Barua%20et%20al.pdf.txt
430ff20ab7bc4fbd2733fbf74511ad9b
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622680/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622680/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Barua et al.pdf
Barua et al.pdf
Open Access publication
application/pdf
3093881
https://repository.helmholtz-hzi.de/bitstream/10033/622680/1/Barua%20et%20al.pdf
178758c81025a7fec02ffab9f65f1223
MD5
1
true
10033/622680
oai:repository.helmholtz-hzi.de:10033/622680
2021-01-15 01:54:29.11
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6227182021-02-06T01:58:19Zcom_10033_620659col_10033_620660
Nakagawa, Rinako
401e60c102b23e0d0a150221be56a082
500
Toboso-Navasa, Amparo
9b99b6808f11a176f990e53ea9f68f43
300
Schips, Marta
74cbcb8b7d11f133b755b8597dd2f438
500
Young, George
cd5231647cab3a39e3ee32dcfbb05788
300
Bhaw-Rosun, Leena
00b04b16ca15fe902276f4433ebbbecd
300
Llorian-Sopena, Miriam
e63c41e3de441934080dc220678af9a0
300
Chakravarty, Probir
0a08cecdc2fe5e92d0666c2735bbefaa
300
Sesay, Abdul Karim
37f0b07c13ab5936dab54e3001df8289
300
Kassiotis, George
bcc425309feac23dd43e02cbdc295034
300
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Calado, Dinis Pedro
39a3c95d35f7b7937355b314b97ff8d0
300
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-02-05T11:11:57Z
2021-02-05T11:11:57Z
2021-01-12
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2016425118. doi: 10.1073/pnas.2016425118.
33419925
10.1073/pnas.2016425118
http://hdl.handle.net/10033/622718
1091-6490
Proceedings of the National Academy of Sciences of the United States of America
Affinity maturation depends on how efficiently germinal centers (GCs) positively select B cells in the light zone (LZ). Positively selected GC B cells recirculate between LZs and dark zones (DZs) and ultimately differentiate into plasmablasts (PBs) and memory B cells (MBCs). Current understanding of the GC reaction presumes that cMyc-dependent positive selection of LZ B cells is a competitive affinity-dependent process; however, this cannot explain the production of GC-derived lower-affinity MBCs or retention of GC B cells with varied affinities. Here, by combining single-cell/bulk RNA sequencing and flow cytometry, we identified and characterized temporally and functionally distinct positively selected cMyc+ GC B cell subpopulations. cMyc+ LZ B cell subpopulations enriched with either higher- or lower-affinity cells diverged soon after permissive positive selection. The former subpopulation contained PB precursors, whereas the latter comprised less proliferative MBC precursors and future DZ entrants. The overall affinity of future DZ entrants was enhanced in the LZ through preferential proliferation of higher-affinity cells. Concurrently, lower-affinity cells were retained in GCs and protected from apoptosis. These findings redefine positive selection as a dynamic process generating three distinct B cell fates and elucidate how positive selection ensures clonal diversity for broad protection.
en
National Academy of Sciences
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
GC B cells
affinity maturation
clonal diversity
memory B cells
positive selection
Permissive selection followed by affinity-based proliferation of GC light zone B cells dictates cell fate and ensures clonal breadth.
Article
118
2
Proceedings of the National Academy of Sciences of the United States of America
United Kingdom
United States
2021-02-05T11:11:58Z
THUMBNAIL
Nakagawa et al.pdf.jpg
Nakagawa et al.pdf.jpg
Generated Thumbnail
image/jpeg
158111
https://repository.helmholtz-hzi.de/bitstream/10033/622718/5/Nakagawa%20et%20al.pdf.jpg
fc075572667449cd8e2baac382934a15
MD5
5
false
TEXT
Nakagawa et al.pdf.txt
Nakagawa et al.pdf.txt
Extracted text
text/plain
86161
https://repository.helmholtz-hzi.de/bitstream/10033/622718/4/Nakagawa%20et%20al.pdf.txt
d6b796515cdf8e4480556034d9cede7f
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622718/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
805
https://repository.helmholtz-hzi.de/bitstream/10033/622718/2/license_rdf
4460e5956bc1d1639be9ae6146a50347
MD5
2
false
ORIGINAL
Nakagawa et al.pdf
Nakagawa et al.pdf
Open Access article
application/pdf
2227927
https://repository.helmholtz-hzi.de/bitstream/10033/622718/1/Nakagawa%20et%20al.pdf
1c990c7926da0e594a9f319854651371
MD5
1
true
10033/622718
oai:repository.helmholtz-hzi.de:10033/622718
2021-02-06 01:58:19.394
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6227272021-02-10T02:32:31Zcom_10033_211390com_10033_620659col_10033_211409col_10033_620660
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Mitra, Tanmay
956bf08ca9fa09db5ec611d4ea747195
500
Bandyopadhyay, Arnab
4746ea0b3b751fb8843b91e75579dbc5
300
Schips, Marta
74cbcb8b7d11f133b755b8597dd2f438
500
Mascheroni, Pietro
f046cc349bd1d2fe247ffdccdb2b8d21
500
Vanella, Patrizio
08b16b123adf78e0af5a039bbfcafec3
500
Lange, Berit
c98e3c484b67f417c9cdd9c8220978fa
500
Binder, Sebastian C
5f59b1f232c7fd9dd584163b14e1b927
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-02-09T10:22:58Z
2021-02-09T10:22:58Z
2021-01-28
BMC Med. 2021 Jan 28;19(1):32. doi: 10.1186/s12916-020-01884-4.
33504336
10.1186/s12916-020-01884-4
http://hdl.handle.net/10033/622727
1741-7015
BMC medicine
Background: SARS-CoV-2 has induced a worldwide pandemic and subsequent non-pharmaceutical interventions (NPIs) to control the spread of the virus. As in many countries, the SARS-CoV-2 pandemic in Germany has led to a consecutive roll-out of different NPIs. As these NPIs have (largely unknown) adverse effects, targeting them precisely and monitoring their effectiveness are essential. We developed a compartmental infection dynamics model with specific features of SARS-CoV-2 that allows daily estimation of a time-varying reproduction number and published this information openly since the beginning of April 2020. Here, we present the transmission dynamics in Germany over time to understand the effect of NPIs and allow adaptive forecasts of the epidemic progression.
Methods: We used a data-driven estimation of the evolution of the reproduction number for viral spreading in Germany as well as in all its federal states using our model. Using parameter estimates from literature and, alternatively, with parameters derived from a fit to the initial phase of COVID-19 spread in different regions of Italy, the model was optimized to fit data from the Robert Koch Institute.
Results: The time-varying reproduction number (Rt) in Germany decreased to <1 in early April 2020, 2-3 weeks after the implementation of NPIs. Partial release of NPIs both nationally and on federal state level correlated with moderate increases in Rt until August 2020. Implications of state-specific Rt on other states and on national level are characterized. Retrospective evaluation of the model shows excellent agreement with the data and usage of inpatient facilities well within the healthcare limit. While short-term predictions may work for a few weeks, long-term projections are complicated by unpredictable structural changes.
Conclusions: The estimated fraction of immunized population by August 2020 warns of a renewed outbreak upon release of measures. A low detection rate prolongs the delay reaching a low case incidence number upon release, showing the importance of an effective testing-quarantine strategy. We show that real-time monitoring of transmission dynamics is important to evaluate the extent of the outbreak, short-term projections for the burden on the healthcare system, and their response to policy changes.
en
BioMedCentral
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
COVID-19
Epidemiology
Healthcare usage
Modeling
Non-pharmaceutical interventions
Reproduction number
SARS-CoV-2
Development of the reproduction number from coronavirus SARS-CoV-2 case data in Germany and implications for political measures.
Article
19
1
32
BMC medicine
International
International
International
England
2021-02-09T10:23:00Z
THUMBNAIL
Khailaie et al.pdf.jpg
Khailaie et al.pdf.jpg
Generated Thumbnail
image/jpeg
93794
https://repository.helmholtz-hzi.de/bitstream/10033/622727/5/Khailaie%20et%20al.pdf.jpg
435c079b6ff199676033c32fd49524db
MD5
5
false
TEXT
Khailaie et al.pdf.txt
Khailaie et al.pdf.txt
Extracted text
text/plain
77146
https://repository.helmholtz-hzi.de/bitstream/10033/622727/4/Khailaie%20et%20al.pdf.txt
b08414ce86f192eb7ea85c106ea0085e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622727/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622727/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Khailaie et al.pdf
Khailaie et al.pdf
Open Access publication
application/pdf
2897928
https://repository.helmholtz-hzi.de/bitstream/10033/622727/1/Khailaie%20et%20al.pdf
3f6c907a83e5ffae43a6d439fb9662ab
MD5
1
true
10033/622727
oai:repository.helmholtz-hzi.de:10033/622727
2021-02-10 02:32:31.993
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6227282021-02-10T02:32:43Zcom_10033_620659com_10033_311308col_10033_620721col_10033_620660
Volk, Valery
471270676314f896c59426533c0b8380
500
Theobald, Sebastian J
b20691f6a8eaced112a6952abc279f6f
500
Danisch, Simon
e414529cf27089a2211c9eadfe2cff3e
500
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Kalbarczyk, Maja
da6e9471badc72ef10d17884f6e0e579
500
Schneider, Andreas
e0f0eceff50ffc02b2f2f318141b786f
500
Bialek-Waldmann, Julia
ccd5312b50382df992b6e26c9a8ae51d
300
Krönke, Nicole
00b68e3ef0498c657651d475c7094a3b
500
Deng, Yun
3147efbc9505aa2e584a7fa6471d678d
300
Eiz-Vesper, Britta
3170523f1490c5988c8616dcbb214477
500
Dragon, Anna Christina
10041bf4d6436646acd27a968e856194
300
von Kaisenberg, Constantin
2bd0ee839910049aaf2222bb2103acdf
Lienenklaus, Stefan
ddc50d051b6287e1137ccffd8f854cbb
600
http://orcid.org/0000-0003-4790-3445
Bleich, Andre
44946b77eccb16008bf430d257affcc9
500
Keck, James
dfe1cc13095b76f46d7c9f96859f3e01
300
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Klawonn, Frank
d40a2d4a33038bf1ab5a9c39b1d4852a
500
Hammerschmidt, Wolfgang
ada81c3e6577346b8ee837b00b0c5d1f
500
Delecluse, Henri-Jacques
c919b67e1fa9875d9897d16512586c73
300
Münz, Christian
3f173837103bb72659e39d7c175dc976
500
Feuerhake, Friedrich
4809c83e5163d63484ac91dc1517b5a2
500
Stripecke, Renata
2a542d77371b05057a72e0d5889405a2
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-02-09T11:10:59Z
2021-02-09T11:10:59Z
2021-01-12
Front Oncol. 2021 Jan 12;10:614876. doi: 10.3389/fonc.2020.614876.
2234-943X
33511078
10.3389/fonc.2020.614876
http://hdl.handle.net/10033/622728
Frontiers in oncology
Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies after solid organ or allogeneic stem cell transplantation. Most PTLD cases are B cell neoplasias carrying Epstein-Barr virus (EBV). A therapeutic approach is reduction of immunosuppression to allow T cells to develop and combat EBV. If this is not effective, approaches include immunotherapies such as monoclonal antibodies targeting CD20 and adoptive T cells. Immune checkpoint inhibition (ICI) to treat EBV+ PTLD was not established clinically due to the risks of organ rejection and graft-versus-host disease. Previously, blockade of the programmed death receptor (PD)-1 by a monoclonal antibody (mAb) during ex vivo infection of mononuclear cells with the EBV/M81+ strain showed lower xenografted lymphoma development in mice. Subsequently, fully humanized mice infected with the EBV/B95-8 strain and treated in vivo with a PD-1 blocking mAb showed aggravation of PTLD and lymphoma development. Here, we evaluated vis-a-vis in fully humanized mice after EBV/B95-8 or EBV/M81 infections the effects of a clinically used PD-1 blocker. Fifteen to 17 weeks after human CD34+ stem cell transplantation, Nod.Rag.Gamma mice were infected with two types of EBV laboratory strains expressing firefly luciferase. Dynamic optical imaging analyses showed systemic EBV infections and this triggered vigorous human CD8+ T cell expansion. Pembrolizumab administered from 2 to 5 weeks post-infections significantly aggravated EBV systemic spread and, for the M81 model, significantly increased the mortality of mice. ICI promoted Ki67+CD30+CD20+EBER+PD-L1+ PTLD with central nervous system (CNS) involvement, mirroring EBV+ CNS PTLD in humans. PD-1 blockade was associated with lower frequencies of circulating T cells in blood and with a profound collapse of CD4+ T cells in lymphatic tissues. Mice treated with pembrolizumab showed an escalation of exhausted T cells expressing TIM-3, and LAG-3 in tissues, higher levels of several human cytokines in plasma and high densities of FoxP3+ regulatory CD4+ and CD8+ T cells in the tumor microenvironment. We conclude that PD-1 blockade during acute EBV infections driving strong CD8+ T cell priming decompensates T cell development towards immunosuppression. Given the variety of preclinical models available, our models conferred a cautionary note indicating that PD-1 blockade aggravated the progression of EBV+ PTLD.
en
Frontiers
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Epstein-Barr Virus (EBV)
PD-1
humanized mice
immune checkpoint inhibition (ICI)
immuno-oncology
lymphoma
pembrolizumab
post-transplant lymphoproliferative disease (PTLD)
PD-1 Blockade Aggravates Epstein-Barr Virus Post-Transplant Lymphoproliferative Disorder in Humanized Mice Resulting in Central Nervous System Involvement and CD4 T Cell Dysregulations.
Article
10
614876
Frontiers in oncology
Switzerland
2021-02-09T11:11:00Z
THUMBNAIL
Volk et al.pdf.jpg
Volk et al.pdf.jpg
Generated Thumbnail
image/jpeg
139645
https://repository.helmholtz-hzi.de/bitstream/10033/622728/5/Volk%20et%20al.pdf.jpg
b39745267611b1aba3149d8ec2543cad
MD5
5
false
TEXT
Volk et al.pdf.txt
Volk et al.pdf.txt
Extracted text
text/plain
101145
https://repository.helmholtz-hzi.de/bitstream/10033/622728/4/Volk%20et%20al.pdf.txt
63a9bff92f4fb6510e04ba1d6e03dd83
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622728/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622728/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Volk et al.pdf
Volk et al.pdf
Open Access publication
application/pdf
9545483
https://repository.helmholtz-hzi.de/bitstream/10033/622728/1/Volk%20et%20al.pdf
c310128762b0b346e5f4953558133654
MD5
1
true
10033/622728
oai:repository.helmholtz-hzi.de:10033/622728
2021-02-10 02:32:43.221
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6227772021-03-20T03:35:54Zcom_10033_620659com_10033_211390col_10033_211409col_10033_620660
Dorn, Florian
2dcc35f5d7133e165b3aa096d40fc903
500
et al.
695ab764f1dc4f9994dfe380686efbf0
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-03-19T12:05:26Z
2021-03-19T12:05:26Z
2020-05-12
http://hdl.handle.net/10033/622777
ifo Schnelldienst digital
[No Abstract available]
de
ifo Institut
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Das gemeinsame Interesse von Gesundheit und Wirtschaft: Eine Szenarienrechnung zur Eindämmung der Corona Pandemie
Article
2021-03-19T12:05:27Z
THUMBNAIL
Dorn et al.pdf.jpg
Dorn et al.pdf.jpg
Generated Thumbnail
image/jpeg
72046
https://repository.helmholtz-hzi.de/bitstream/10033/622777/5/Dorn%20et%20al.pdf.jpg
2cdcc88516bd399240101bad70587070
MD5
5
false
TEXT
Dorn et al.pdf.txt
Dorn et al.pdf.txt
Extracted text
text/plain
47404
https://repository.helmholtz-hzi.de/bitstream/10033/622777/4/Dorn%20et%20al.pdf.txt
0f9dff904030ccfac99457959b0fdca9
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622777/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1031
https://repository.helmholtz-hzi.de/bitstream/10033/622777/2/license_rdf
934f4ca17e109e0a05eaeaba504d7ce4
MD5
2
false
ORIGINAL
Dorn et al.pdf
Dorn et al.pdf
from Open Access journal
application/pdf
1248697
https://repository.helmholtz-hzi.de/bitstream/10033/622777/1/Dorn%20et%20al.pdf
25c7b2f6f860fa2b9f713cb3d17d5361
MD5
1
true
10033/622777
oai:repository.helmholtz-hzi.de:10033/622777
2021-03-20 03:35:54.968
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6227902021-03-25T01:32:00Zcom_10033_620659col_10033_620660
Merino Tejero, Elena
139e39373800ba841ee600a79c460137
300
Lashgari, Danial
f1e860fd0227f0620e452ff2b2b240cc
300
García-Valiente, Rodrigo
bd7ee9a7292411563399f40f5bf5a6da
300
Gao, Xuefeng
4d3b5cd3cc050099fdee9c2adc0b2347
300
Crauste, Fabien
4ff55c8b65d7c3e7cab3a8808bf2b0cc
300
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Martínez, María Rodríguez
6885f75aff6cb6d1d66f375f66d99a8b
300
van Ham, S Marieke
b86d7a1a35f371e330e78cbc8d5f8dbe
300
Guikema, Jeroen E J
35a3b5bf458edb1c9db130f7e1b079e9
300
Hoefsloot, Huub
5aa8e1b1dbc2103697b57c3e31961338
300
van Kampen, Antoine H C
da948ac2c0240941c1af28d1f3842ab7
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-03-24T10:58:20Z
2021-03-24T10:58:20Z
2021-02-05
Front Immunol. 2021 Feb 5;11:620716. doi: 10.3389/fimmu.2020.620716.
33613551
10.3389/fimmu.2020.620716
http://hdl.handle.net/10033/622790
1664-3224
Frontiers in immunology
Germinal centers play a key role in the adaptive immune system since they are able to produce memory B cells and plasma cells that produce high affinity antibodies for an effective immune protection. The mechanisms underlying cell-fate decisions are not well understood but asymmetric division of antigen, B-cell receptor affinity, interactions between B-cells and T follicular helper cells (triggering CD40 signaling), and regulatory interactions of transcription factors have all been proposed to play a role. In addition, a temporal switch from memory B-cell to plasma cell differentiation during the germinal center reaction has been shown. To investigate if antigen affinity-based Tfh cell help recapitulates the temporal switch we implemented a multiscale model that integrates cellular interactions with a core gene regulatory network comprising BCL6, IRF4, and BLIMP1. Using this model we show that affinity-based CD40 signaling in combination with asymmetric division of B-cells result in switch from memory B-cell to plasma cell generation during the course of the germinal center reaction. We also show that cell fate division is unlikely to be (solely) based on asymmetric division of Ag but that BLIMP1 is a more important factor. Altogether, our model enables to test the influence of molecular modulations of the CD40 signaling pathway on the production of germinal center output cells.
en
Frontiers
info:eu-repo/grantAgreement/H2020/765158
openAccess
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
CD40 signaling
T follicular helper cell
germinal center
multiscale model
plasma cell differentiation
Multiscale Modeling of Germinal Center Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells Differentiation as Regulated by Antigen Affinity-Based Tfh Cell Help.
Article
11
620716
Frontiers in immunology
Switzerland
2021-03-24T10:58:20Z
THUMBNAIL
T5ejero et al.pdf.jpg
T5ejero et al.pdf.jpg
Generated Thumbnail
image/jpeg
129188
https://repository.helmholtz-hzi.de/bitstream/10033/622790/5/T5ejero%20et%20al.pdf.jpg
aeeac13c7c5dab57a0bd745153d66ac4
MD5
5
false
TEXT
T5ejero et al.pdf.txt
T5ejero et al.pdf.txt
Extracted text
text/plain
71231
https://repository.helmholtz-hzi.de/bitstream/10033/622790/4/T5ejero%20et%20al.pdf.txt
583b558783a60777027bb21014ee64da
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622790/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622790/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
T5ejero et al.pdf
T5ejero et al.pdf
Open Access publication
application/pdf
3656392
https://repository.helmholtz-hzi.de/bitstream/10033/622790/1/T5ejero%20et%20al.pdf
253eaa544e55691701f29fb1316b7ebd
MD5
1
true
10033/622790
oai:repository.helmholtz-hzi.de:10033/622790
2021-03-25 01:32:00.914
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBIZWxtaG9sdHogWmVudHJ1bSBm77+9ciBJbmZla3Rpb25zZm9yc2NodW5nIFJlcG9zaXRvcnkgKEhaSSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBIWkkgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgSFpJIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgSFpJIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gSFpJLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpIWkkgd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=
oai:repository.helmholtz-hzi.de:10033/6228212021-04-07T01:29:41Zcom_10033_620659col_10033_620660
Rastogi, Ananya
01f1c39aa3ebf2ec475efcc729c8b3f3
500
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Halle, Stephan
08506b772c0146cd365008838a3ef2b6
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-04-06T11:29:54Z
2021-04-06T11:29:54Z
2020-12-28
PLoS Comput Biol. 2020 Dec 28;16(12):e1008428. doi: 10.1371/journal.pcbi.1008428.
33370254
10.1371/journal.pcbi.1008428
http://hdl.handle.net/10033/622821
1553-7358
PLoS computational biology
In vivo imaging of cytotoxic T lymphocyte (CTL) killing activity revealed that infected cells have a higher observed probability of dying after multiple contacts with CTLs. We developed a three-dimensional agent-based model to discriminate different hypotheses about how infected cells get killed based on quantitative 2-photon in vivo observations. We compared a constant CTL killing probability with mechanisms of signal integration in CTL or infected cells. The most likely scenario implied increased susceptibility of infected cells with increasing number of CTL contacts where the total number of contacts was a critical factor. However, when allowing in silico T cells to initiate new interactions with apoptotic target cells (zombie contacts), a contact history independent killing mechanism was also in agreement with experimental datasets. The comparison of observed datasets to simulation results, revealed limitations in interpreting 2-photon data, and provided readouts to distinguish CTL killing models.
en
PLOS
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments.
Article
16
12
e1008428
PLoS computational biology
United States
2021-04-06T11:29:54Z
THUMBNAIL
Rastogi et al.pdf.jpg
Rastogi et al.pdf.jpg
Generated Thumbnail
image/jpeg
101177
https://repository.helmholtz-hzi.de/bitstream/10033/622821/5/Rastogi%20et%20al.pdf.jpg
f8626b786f19823e6610c55030bf5090
MD5
5
false
TEXT
Rastogi et al.pdf.txt
Rastogi et al.pdf.txt
Extracted text
text/plain
97874
https://repository.helmholtz-hzi.de/bitstream/10033/622821/4/Rastogi%20et%20al.pdf.txt
ea03d6d478f0b9e54685a83ec6c05345
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622821/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622821/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Rastogi et al.pdf
Rastogi et al.pdf
Open Access publication
application/pdf
3035613
https://repository.helmholtz-hzi.de/bitstream/10033/622821/1/Rastogi%20et%20al.pdf
b8a3f8de28402ea9a87240a66ca1f0d2
MD5
1
true
10033/622821
oai:repository.helmholtz-hzi.de:10033/622821
2021-04-07 01:29:41.623
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6228232021-04-08T01:40:59Zcom_10033_128109com_10033_620659com_10033_620591col_10033_128110col_10033_620724col_10033_620660
Elfaki, Yassin
b7ac992d2de87d19940f2622e92869f0
500
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Binz, Christoph
f3fc7a6581143e981a0c1b32854ee552
300
Falk, Christine S
84fa0c3390a25e71bc272964dddb40ff
Bruder, Dunja
b5a4f0fe11461388fa1e79487e3fb00e
600
http://orcid.org/0000-0003-3066-189X
Prinz, Immo
4a3aae181793927d1b7907eb1a77b222
500
Floess, Stefan
5ffe089d50f6ea39d568657c60ebcc8f
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Huehn, Jochen
81855dd40035a02edad8ee83ce210282
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-04-07T14:24:38Z
2021-04-07T14:24:38Z
2021-02-26
Eur J Immunol. 2021 Feb 26. doi: 10.1002/eji.202048981. Epub ahead of print.
33638148
10.1002/eji.202048981
http://hdl.handle.net/10033/622823
1521-4141
European journal of immunology
Foxp3+ Treg cells, which are crucial for maintenance of self-tolerance, mainly develop within the thymus, where they arise from CD25+ Foxp3- or CD25- Foxp3+ Treg cell precursors. Although it is known that infections can cause transient thymic involution, the impact of infection-induced thymus atrophy on thymic Treg (tTreg) cell development is unknown. Here, we infected mice with influenza A virus (IAV) and studied thymocyte population dynamics post infection. IAV infection caused a massive, but transient thymic involution, dominated by a loss of CD4+ CD8+ double-positive (DP) thymocytes, which was accompanied by a significant increase in the frequency of CD25+ Foxp3+ tTreg cells. Differential apoptosis susceptibility could be experimentally excluded as a reason for the relative tTreg cell increase, and mathematical modeling suggested that enhanced tTreg cell generation cannot explain the increased frequency of tTreg cells. Yet, an increased death of DP thymocytes and augmented exit of single-positive (SP) thymocytes was suggested to be causative. Interestingly, IAV-induced thymus atrophy resulted in a significantly reduced T-cell receptor (TCR) repertoire diversity of newly produced tTreg cells. Taken together, IAV-induced thymus atrophy is substantially altering the dynamics of major thymocyte populations, finally resulting in a relative increase of tTreg cells with an altered TCR repertoire.
en
Wiley-VCH
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Foxp3+ Treg cells ⋅ Influenza A virus ⋅ Mathematical modeling ⋅ Ordinary differential equations ⋅ Thymus atrophy
Influenza A virus-induced thymus atrophy differentially affects dynamics of conventional and regulatory T-cell development in mice.
Article
European journal of immunology
Germany
2021-04-07T14:24:38Z
THUMBNAIL
Elfaki et al.pdf.jpg
Elfaki et al.pdf.jpg
Generated Thumbnail
image/jpeg
97847
https://repository.helmholtz-hzi.de/bitstream/10033/622823/5/Elfaki%20et%20al.pdf.jpg
d43c44c13944032b496275f2bd03b1e1
MD5
5
false
TEXT
Elfaki et al.pdf.txt
Elfaki et al.pdf.txt
Extracted text
text/plain
81273
https://repository.helmholtz-hzi.de/bitstream/10033/622823/4/Elfaki%20et%20al.pdf.txt
aa0ee7a64544d397e1524bf06898e655
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622823/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622823/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Elfaki et al.pdf
Elfaki et al.pdf
Open Access publication
application/pdf
1620632
https://repository.helmholtz-hzi.de/bitstream/10033/622823/1/Elfaki%20et%20al.pdf
b0ff8726d0a952cd7f7a6f43689ebd83
MD5
1
true
10033/622823
oai:repository.helmholtz-hzi.de:10033/622823
2021-04-08 01:40:59.35
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6228532021-05-04T01:38:20Zcom_10033_620659col_10033_620660
Barua, Arnab
e5233ccc288d2dd0de9728c41dcbaf04
500
Syga, Simon
7e7c5b4aa2be98c6e231ecca43e79caa
300
Mascheroni, Pietro
f046cc349bd1d2fe247ffdccdb2b8d21
500
Kavallaris, Nikos
a950a06bc45e908f066fc4fe9c11d5d8
300
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Deutsch, Andreas
5d5b35cc14130c278f0f88d48746681b
300
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-05-03T13:21:14Z
2021-05-03T13:21:14Z
2020-12-01
(2020) New Journal of Physics,22(12)art.no: 123034.
13672630
10.1088/1367-2630/abcb2e
http://hdl.handle.net/10033/622853
New Journal of Physics
2-s2.0-85097945599
SCOPUS_ID:85097945599
Cellular decision making allows cells to assume functionally different phenotypes in response to microenvironmental cues, with or without genetic change. It is an open question, how individual cell decisions influence the dynamics at the tissue level. Here, we study spatio-temporal pattern formation in a population of cells exhibiting phenotypic plasticity, which is a paradigm of cell decision making. We focus on the migration/resting and the migration/proliferation plasticity which underly the epithelial-mesenchymal transition and the go or grow dichotomy. We assume that cells change their phenotype in order to minimize their microenvironmental entropy following the LEUP (Least microEnvironmental Uncertainty Principle) hypothesis. In turn, we study the impact of the LEUP-driven migration/resting and migration/proliferation plasticity on the corresponding multicellular spatio-temporal dynamics with a stochastic cell-based mathematical model for the spatio-temporal dynamics of the cell phenotypes. In the case of the go or rest plasticity, a corresponding mean-field approximation allows to identify a bistable switching mechanism between a diffusive (fluid) and an epithelial (solid) tissue phase which depends on the sensitivity of the phenotypes to the environment. For the go or grow plasticity, we show the possibility of Turing pattern formation for the ‘solid’ tissue phase and its relation with the parameters of the LEUP-driven cell decisions.
Volkswagen Foundation
Institute of Physics
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Cell-decision making
Fluid-to-solid transition
Langevin equations
Least microEnvironmental uncertainty principle (LEUP)
Mean-field theory
Phenotypic plasticity
Entropy-driven cell decision-making predicts ‘fluid-to-solid’ transition in multicellular systems
Article
22
12
New Journal of Physics
2021-05-03T13:21:15Z
THUMBNAIL
Barua et al.pdf.jpg
Barua et al.pdf.jpg
Generated Thumbnail
image/jpeg
21360
https://repository.helmholtz-hzi.de/bitstream/10033/622853/5/Barua%20et%20al.pdf.jpg
9e76b4fba929c3dbcbfea399ca40e6b1
MD5
5
false
TEXT
Barua et al.pdf.txt
Barua et al.pdf.txt
Extracted text
text/plain
58231
https://repository.helmholtz-hzi.de/bitstream/10033/622853/4/Barua%20et%20al.pdf.txt
887be59b2c10a8f02f51f31392c0596c
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622853/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622853/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Barua et al.pdf
Barua et al.pdf
Open Access publication
application/pdf
3110972
https://repository.helmholtz-hzi.de/bitstream/10033/622853/1/Barua%20et%20al.pdf
7fcaa80745ed5e99b0357cba2e825f67
MD5
1
true
10033/622853
oai:repository.helmholtz-hzi.de:10033/622853
2021-05-04 01:38:20.897
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6228702021-05-13T01:51:34Zcom_10033_620659col_10033_620660
Tretter, Felix
84506c01ce40320cac6c9d8988429398
300
Wolkenhauer, Olaf
a47af56b8317499d49705cf7d0524aed
300
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Dietrich, Johannes W
b7fd1696d2637e24af605e19887e6ceb
300
Green, Sara
980cce2d7f645ffd2676a74799efdff0
300
Marcum, James
2f3940b3c539fde2ee7ca787f4e30b29
300
Weckwerth, Wolfram
708e798fe45b634beab64fca781f2632
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-05-12T11:33:02Z
2021-05-12T11:33:02Z
2021-03-29
Front Med (Lausanne). 2021 Mar 29;8:640974. doi: 10.3389/fmed.2021.640974.
2296-858X
33855036
10.3389/fmed.2021.640974
http://hdl.handle.net/10033/622870
Frontiers in medicine
Precision medicine and molecular systems medicine (MSM) are highly utilized and successful approaches to improve understanding, diagnosis, and treatment of many diseases from bench-to-bedside. Especially in the COVID-19 pandemic, molecular techniques and biotechnological innovation have proven to be of utmost importance for rapid developments in disease diagnostics and treatment, including DNA and RNA sequencing technology, treatment with drugs and natural products and vaccine development. The COVID-19 crisis, however, has also demonstrated the need for systemic thinking and transdisciplinarity and the limits of MSM: the neglect of the bio-psycho-social systemic nature of humans and their context as the object of individual therapeutic and population-oriented interventions. COVID-19 illustrates how a medical problem requires a transdisciplinary approach in epidemiology, pathology, internal medicine, public health, environmental medicine, and socio-economic modeling. Regarding the need for conceptual integration of these different kinds of knowledge we suggest the application of general system theory (GST). This approach endorses an organism-centered view on health and disease, which according to Ludwig von Bertalanffy who was the founder of GST, we call Organismal Systems Medicine (OSM). We argue that systems science offers wider applications in the field of pathology and can contribute to an integrative systems medicine by (i) integration of evidence across functional and structural differentially scaled subsystems, (ii) conceptualization of complex multilevel systems, and (iii) suggesting mechanisms and non-linear relationships underlying the observed phenomena. We underline these points with a proposal on multi-level systems pathology including neurophysiology, endocrinology, immune system, genetics, and general metabolism. An integration of these areas is necessary to understand excess mortality rates and polypharmacological treatments. In the pandemic era this multi-level systems pathology is most important to assess potential vaccines, their effectiveness, short-, and long-time adverse effects. We further argue that these conceptual frameworks are not only valid in the COVID-19 era but also important to be integrated in a medicinal curriculum.
en
Frontiers
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Organismal Systems Medicine
dynamic equilibrium
excess mortality rate
multi organ disease
multi-level view model
polypharmacology
systems theory
The Quest for System-Theoretical Medicine in the COVID-19 Era.
Article
8
640974
Frontiers in medicine
Switzerland
2021-05-12T11:33:03Z
THUMBNAIL
Tretter et al.pdf.jpg
Tretter et al.pdf.jpg
Generated Thumbnail
image/jpeg
131000
https://repository.helmholtz-hzi.de/bitstream/10033/622870/5/Tretter%20et%20al.pdf.jpg
11277a8d8398b0f6b2f89574a4ddc7fa
MD5
5
false
TEXT
Tretter et al.pdf.txt
Tretter et al.pdf.txt
Extracted text
text/plain
67903
https://repository.helmholtz-hzi.de/bitstream/10033/622870/4/Tretter%20et%20al.pdf.txt
7f784d3e31f87d6846d0fd73087ca3ec
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622870/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622870/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Tretter et al.pdf
Tretter et al.pdf
Open Access publication
application/pdf
1892230
https://repository.helmholtz-hzi.de/bitstream/10033/622870/1/Tretter%20et%20al.pdf
b2851219fdbbc06a5f458500a5647563
MD5
1
true
10033/622870
oai:repository.helmholtz-hzi.de:10033/622870
2021-05-13 01:51:34.805
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6229322021-07-10T01:44:11Zcom_10033_620659col_10033_620660
Linden, Matthias
6cc1b81eafb976574267082f7a3352bd
300
Dehning, Jonas
edc2915c7ec55a9d5bfa739f76180306
300
Mohr, Sebastian B
e3a186ae3196d4bffe669e8920cfbcc0
300
Mohring, Jan
7f703600a74e3ef89bd29e964eb7c5f0
300
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Pigeot, Iris
0237f630326e842ff6425bd891fd03f9
500
Schöbel, Anita
84249ac766f3c1301a032d603921737d
300
Priesemann, Viola
c901a637bfe6c597ebd06563f3452c86
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-07-09T09:14:26Z
2021-07-09T09:14:26Z
Dtsch Arztebl Int 2020; 117: 790–1. DOI: 10.3238/arztebl.2020.0790
33533714
10.3238/arztebl.2020.0790
http://hdl.handle.net/10033/622932
1866-0452
Deutsches Arzteblatt international
PMC7930464
[No abstract available]
en
Dt. Ärzte-Verl.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930464/
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Case Numbers Beyond Contact Tracing Capacity Are Endangering the Containment of COVID-19.
Letter
117
46
790
791
Deutsches Arzteblatt international
Germany
2021-07-09T09:14:27Z
THUMBNAIL
Linden et al.pdf.jpg
Linden et al.pdf.jpg
Generated Thumbnail
image/jpeg
133298
https://repository.helmholtz-hzi.de/bitstream/10033/622932/5/Linden%20et%20al.pdf.jpg
343d839cf67f528866b28754e1487382
MD5
5
false
TEXT
Linden et al.pdf.txt
Linden et al.pdf.txt
Extracted text
text/plain
10174
https://repository.helmholtz-hzi.de/bitstream/10033/622932/4/Linden%20et%20al.pdf.txt
23c89b0b590e8788aecbccd576fa1c2a
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622932/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622932/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Linden et al.pdf
Linden et al.pdf
freely accessible correspondence
application/pdf
312222
https://repository.helmholtz-hzi.de/bitstream/10033/622932/1/Linden%20et%20al.pdf
187632bd84e534356cf73aeac8134565
MD5
1
true
10033/622932
oai:repository.helmholtz-hzi.de:10033/622932
2021-07-10 01:44:11.451
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6229472021-08-04T10:24:30Zcom_10033_620659col_10033_620660
Arulraj, Theinmozhi
7f81f4a361c7601256a026aefaf11acd
500
Binder, Sebastian C
ca9fc32341dea761712a6ca7f0d7308b
600
http://orcid.org/0000-0003-1169-1786
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-07-21T10:05:30Z
2021-07-21T10:05:30Z
2021-02-19
J Immunol. 2021 Apr 1;206(7):1436-1442. doi: 10.4049/jimmunol.2001355. Epub 2021 Feb 19.
33608455
10.4049/jimmunol.2001355
http://hdl.handle.net/10033/622947
1550-6606
Journal of immunology (Baltimore, Md. : 1950)
en
American Association of Immunologists
info:eu-repo/grantAgreement/EC/H2020/765158
openAccess
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells.
Article
206
7
1436
1442
Journal of immunology (Baltimore, Md. : 1950)
United States
2021-07-21T10:05:30Z
THUMBNAIL
Arulraj et al.pdf.jpg
Arulraj et al.pdf.jpg
Generated Thumbnail
image/jpeg
91966
https://repository.helmholtz-hzi.de/bitstream/10033/622947/5/Arulraj%20et%20al.pdf.jpg
b8eff5e028eaf347ab5efe21cdff6566
MD5
5
false
TEXT
Arulraj et al.pdf.txt
Arulraj et al.pdf.txt
Extracted text
text/plain
954
https://repository.helmholtz-hzi.de/bitstream/10033/622947/4/Arulraj%20et%20al.pdf.txt
daf1f743719a33c16c95690aac18f930
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/622947/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/622947/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Arulraj et al.pdf
Arulraj et al.pdf
article with supplemental figures
application/pdf
4026679
https://repository.helmholtz-hzi.de/bitstream/10033/622947/1/Arulraj%20et%20al.pdf
6132de3b56c4e1c8d5420c0d79c1762f
MD5
1
true
10033/622947
oai:repository.helmholtz-hzi.de:10033/622947
2021-08-04 10:24:30.741
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6230172021-09-09T01:53:12Zcom_10033_128109com_10033_620659col_10033_128110col_10033_620660
Arulraj, Theinmozhi
7f81f4a361c7601256a026aefaf11acd
500
Binder, Sebastian C
ca9fc32341dea761712a6ca7f0d7308b
500
http://orcid.org/0000-0003-1169-1786
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-09-08T12:17:09Z
2021-09-08T12:17:09Z
2021-07-07
Front Immunol. 2021 Jul 7;12:705240. doi: 10.3389/fimmu.2021.705240.
34305944
10.3389/fimmu.2021.705240
http://hdl.handle.net/10033/623017
1664-3224
Frontiers in immunology
Germinal Centres (GCs) are transient structures in secondary lymphoid organs, where affinity maturation of B cells takes place following an infection. While GCs are responsible for protective antibody responses, dysregulated GC reactions are associated with autoimmune disease and B cell lymphoma. Typically, 'normal' GCs persist for a limited period of time and eventually undergo shutdown. In this review, we focus on an important but unanswered question - what causes the natural termination of the GC reaction? In murine experiments, lack of antigen, absence or constitutive T cell help leads to premature termination of the GC reaction. Consequently, our present understanding is limited to the idea that GCs are terminated due to a decrease in antigen access or changes in the nature of T cell help. However, there is no direct evidence on which biological signals are primarily responsible for natural termination of GCs and a mechanistic understanding is clearly lacking. We discuss the present understanding of the GC shutdown, from factors impacting GC dynamics to changes in cellular interactions/dynamics during the GC lifetime. We also address potential missing links and remaining questions in GC biology, to facilitate further studies to promote a better understanding of GC shutdown in infection and immune dysregulation.
en
Frontiers
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
B cell lymphoma
antibody responses
chronic germinal centres
ectopic germinal centres
germinal centre shutdown
vaccination
Germinal Centre Shutdown.
Article
12
705240
Frontiers in immunology
Switzerland
2021-09-08T12:17:10Z
THUMBNAIL
Arulraj et al.pdf.jpg
Arulraj et al.pdf.jpg
Generated Thumbnail
image/jpeg
115566
https://repository.helmholtz-hzi.de/bitstream/10033/623017/5/Arulraj%20et%20al.pdf.jpg
f989766629aee60ce344548ae701cc80
MD5
5
false
TEXT
Arulraj et al.pdf.txt
Arulraj et al.pdf.txt
Extracted text
text/plain
106382
https://repository.helmholtz-hzi.de/bitstream/10033/623017/4/Arulraj%20et%20al.pdf.txt
dd8d680896051137e228a64ba643726e
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623017/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623017/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Arulraj et al.pdf
Arulraj et al.pdf
Open Access publication
application/pdf
930120
https://repository.helmholtz-hzi.de/bitstream/10033/623017/1/Arulraj%20et%20al.pdf
45e185a248e39faa356a1bd71202cea1
MD5
1
true
10033/623017
oai:repository.helmholtz-hzi.de:10033/623017
2021-09-09 01:53:12.362
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6230402021-09-22T01:53:11Zcom_10033_620659col_10033_620660
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-09-21T09:04:49Z
2021-09-21T09:04:49Z
2021-08-24
Cell Rep. 2021 Aug 24;36(8):109552. doi: 10.1016/j.celrep.2021.109552. PMID: 34433043.
34433043
10.1016/j.celrep.2021.109552
http://hdl.handle.net/10033/623040
2211-1247
Cell reports
The selection of B cells (BCs) in germinal centers (GCs) is pivotal to the generation of high-affinity antibodies and memory BCs, but it lacks global understanding. Based on the idea of a single Tfh-cell signal that controls BC selection and division, experiments appear contradictory. Here, we use the current knowledge on the molecular pathways of GC BCs to develop a theory of GC BC selection and division based on the dynamics of molecular factors. This theory explains the seemingly contradictory experiments by the separation of signals for BC fate decision from signals controlling the number of BC divisions. Three model variants are proposed and experiments are predicted that allow one to distinguish those. Understanding information processing in molecular BC states is critical for targeted immune interventions, and the proposed theory implies that selection and division can be controlled independently in GC reactions.
en
Cell Press
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
B cell division
B cell selection
B cell signaling
FoxO1
affinity maturation
c-Myc
computer simulation
germinal center
mTOR
mathematical model
A molecular theory of germinal center B cell selection and division.
Article
36
8
109552
Cell reports
United States
2021-09-21T09:04:49Z
THUMBNAIL
Meyer-Herrmann.pdf.jpg
Meyer-Herrmann.pdf.jpg
Generated Thumbnail
image/jpeg
75136
https://repository.helmholtz-hzi.de/bitstream/10033/623040/7/Meyer-Herrmann.pdf.jpg
4b4c7436606b772997e73ed4c33827d7
MD5
7
false
Meyer-Herrmann_suppl. figures S1 to S16.pdf.jpg
Meyer-Herrmann_suppl. figures S1 to S16.pdf.jpg
Generated Thumbnail
image/jpeg
10237
https://repository.helmholtz-hzi.de/bitstream/10033/623040/9/Meyer-Herrmann_suppl.%20figures%20S1%20to%20S16.pdf.jpg
c6b7baeaf5f63286d3834a346ae46833
MD5
9
false
Meyer-Herrmann_suppl.Doc S2.pdf.jpg
Meyer-Herrmann_suppl.Doc S2.pdf.jpg
Generated Thumbnail
image/jpeg
75136
https://repository.helmholtz-hzi.de/bitstream/10033/623040/11/Meyer-Herrmann_suppl.Doc%20S2.pdf.jpg
4b4c7436606b772997e73ed4c33827d7
MD5
11
false
elsevier-thumbnail.png
application/octet-stream
43322
https://repository.helmholtz-hzi.de/bitstream/10033/623040/12/elsevier-thumbnail.png
41cd4cabac61daeb48c6eca7d1499422
MD5
12
false
TEXT
Meyer-Herrmann.pdf.txt
Meyer-Herrmann.pdf.txt
Extracted text
text/plain
103706
https://repository.helmholtz-hzi.de/bitstream/10033/623040/6/Meyer-Herrmann.pdf.txt
2b31e0837e2fd827100445b1a1b99957
MD5
6
false
Meyer-Herrmann_suppl. figures S1 to S16.pdf.txt
Meyer-Herrmann_suppl. figures S1 to S16.pdf.txt
Extracted text
text/plain
154
https://repository.helmholtz-hzi.de/bitstream/10033/623040/8/Meyer-Herrmann_suppl.%20figures%20S1%20to%20S16.pdf.txt
7d8323628ba25f9671dfc528c00ab186
MD5
8
false
Meyer-Herrmann_suppl.Doc S2.pdf.txt
Meyer-Herrmann_suppl.Doc S2.pdf.txt
Extracted text
text/plain
103860
https://repository.helmholtz-hzi.de/bitstream/10033/623040/10/Meyer-Herrmann_suppl.Doc%20S2.pdf.txt
3c5e4eefa5ad3c5d8e2a3cb0218bb6dd
MD5
10
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623040/5/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
5
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623040/4/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
4
false
ORIGINAL
Meyer-Herrmann.pdf
Meyer-Herrmann.pdf
Open Access publication
application/pdf
4603658
https://repository.helmholtz-hzi.de/bitstream/10033/623040/1/Meyer-Herrmann.pdf
5bab7987badc117631641f4015c8ce8d
MD5
1
true
Meyer-Herrmann_suppl. figures S1 to S16.pdf
Meyer-Herrmann_suppl. figures S1 to S16.pdf
supplemental figures S1 to S16
application/pdf
16522770
https://repository.helmholtz-hzi.de/bitstream/10033/623040/2/Meyer-Herrmann_suppl.%20figures%20S1%20to%20S16.pdf
ecc5ec10c95011d1dd1b63770ce161eb
MD5
2
false
Meyer-Herrmann_suppl.Doc S2.pdf
Meyer-Herrmann_suppl.Doc S2.pdf
supplemental document S2
application/pdf
21123514
https://repository.helmholtz-hzi.de/bitstream/10033/623040/3/Meyer-Herrmann_suppl.Doc%20S2.pdf
ef3f85189ee6c4041882e2201ef89c86
MD5
3
false
10033/623040
oai:repository.helmholtz-hzi.de:10033/623040
2021-09-22 01:53:11.847
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6230602021-10-05T03:23:31Zcom_10033_620659col_10033_620660
Priesemann, Viola
c901a637bfe6c597ebd06563f3452c86
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Pigeot, Iris
0237f630326e842ff6425bd891fd03f9
500
Schöbel, Anita
84249ac766f3c1301a032d603921737d
500
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-10-04T14:27:18Z
2021-10-04T14:27:18Z
2021-07-30
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2021 Sep;64(9):1058-1066. German. doi: 10.1007/s00103-021-03390-1. Epub 2021 Jul 30.
34328524
10.1007/s00103-021-03390-1
http://hdl.handle.net/10033/623060
1437-1588
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
After the global outbreak of the COVID-19 pandemic, an infection dynamic of immense extent developed. Since then, numerous measures have been taken to bring the infection under control. This was very successful in the spring of 2020, while the number of infections rose sharply the following autumn. To predict the occurrence of infections, epidemiological models are used. These are in principle a very valuable tool in pandemic management. However, they still partly need to be based on assumptions regarding the transmission routes and possible drivers of the infection dynamics. Despite numerous individual approaches, systematic epidemiological data are still lacking with which, for example, the effectiveness of individual measures could be quantified. Such information generated in studies is needed to enable reliable predictions regarding the further course of the pandemic. Thereby, the complexity of the models could develop hand in hand with the complexity of the available data. In this article, after delineating two basic classes of models, the contribution of epidemiological models to the assessment of various central aspects of the pandemic, such as the reproduction rate, the number of unreported cases, infection fatality rate, and the consideration of regionality, is shown. Subsequently, the use of the models to quantify the impact of measures and the effects of the "test-trace-isolate" strategy is described. In the concluding discussion, the limitations of such modelling approaches are juxtaposed with their advantages.
de
Springer
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Agent-based models
Compartmental models
Dark figure
Infection fatality rate
Reproductive number
[The contribution of epidemiological models to the description of the outbreak of the COVID-19 pandemic].
Review
64
9
1058
1066
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
Germany
2021-10-04T14:27:18Z
THUMBNAIL
Priesemann et al.pdf.jpg
Priesemann et al.pdf.jpg
Generated Thumbnail
image/jpeg
105787
https://repository.helmholtz-hzi.de/bitstream/10033/623060/5/Priesemann%20et%20al.pdf.jpg
b9a2ad87d59a2b4bc69da34ce334abf1
MD5
5
false
TEXT
Priesemann et al.pdf.txt
Priesemann et al.pdf.txt
Extracted text
text/plain
46228
https://repository.helmholtz-hzi.de/bitstream/10033/623060/4/Priesemann%20et%20al.pdf.txt
bdd4a42c26518c6264bfdf00ed6a36f0
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623060/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623060/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Priesemann et al.pdf
Priesemann et al.pdf
Open Access publication
application/pdf
2718037
https://repository.helmholtz-hzi.de/bitstream/10033/623060/1/Priesemann%20et%20al.pdf
85a4046f66f8e86fd98bb70d3f607949
MD5
1
true
10033/623060
oai:repository.helmholtz-hzi.de:10033/623060
2021-10-05 03:23:31.075
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6230682021-10-09T01:59:22Zcom_10033_620659col_10033_620660
Kühn, Martin J
e05f04a43b6e13e59f02cf0c4b2abda8
300
Abele, Daniel
00e27320ba4725b21ab200ac53b215ac
300
Mitra, Tanmay
956bf08ca9fa09db5ec611d4ea747195
500
Koslow, Wadim
c7e88f0f8579f1220d4d68ff3c2128db
300
Abedi, Majid
878c672926d31cb857859c0045201e13
300
Rack, Kathrin
b156fc8d4ecc5d1d6d1375d21871fc49
300
Siggel, Martin
ab729f8c578a36268f549671d07dc948
300
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Klitz, Margrit
cd8956d9b7fb9c63fde32d4f92c30d29
300
Binder, Sebastian
cd17c497203cd901f428297003a48de7
500
Spataro, Luca
dd97aa5f920f2ce2bde723de7770c82e
300
Gilg, Jonas
c91dbde2139165b1cdeda295a9b2453d
300
Kleinert, Jan
ce582076a42d4a6e6fcb3937b55a4b36
300
Häberle, Matthias
097ffbe84a30b13d83ce6ea7811bbe33
300
Plötzke, Lena
b3fa90b3bcc856cb8511328530b65d5a
300
Spinner, Christoph D
28eedba24e72046a2d8a4c240f0985a9
300
Stecher, Melanie
39d55a7acc51867eb8ee8b54eb3895e5
500
Zhu, Xiao Xiang
591d5ba82a56eb684ad7d0d7543bb823
300
Basermann, Achim
8988a03e4c6c7d4569f9b9022a0c3fdf
300
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
http://orcid.org/0000-0002-4300-2474
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2021-10-08T14:09:34Z
2021-10-08T14:09:34Z
2021-06-30
Math Biosci. 2021 Sep;339:108648. doi: 10.1016/j.mbs.2021.108648. Epub 2021 Jun 30. PMID: 34216635.
34216635
10.1016/j.mbs.2021.108648
http://hdl.handle.net/10033/623068
1879-3134
Mathematical biosciences
on-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coronavirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic prepandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.
en
Elsevier
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Coronavirus disease
Covid-19
Forecast
Mitigation
Non-pharmaceutical interventions
SARS-CoV-2
Assessment of effective mitigation and prediction of the spread of SARS-CoV-2 in Germany using demographic information and spatial resolution.
Article
339
108648
Mathematical biosciences
United States
2021-10-08T14:09:35Z
THUMBNAIL
Kuehn et al.pdf.jpg
Kuehn et al.pdf.jpg
Generated Thumbnail
image/jpeg
88942
https://repository.helmholtz-hzi.de/bitstream/10033/623068/5/Kuehn%20et%20al.pdf.jpg
a545be909822c5696b8db5498d9d8723
MD5
5
false
elsevier-thumbnail.png
application/octet-stream
60697
https://repository.helmholtz-hzi.de/bitstream/10033/623068/6/elsevier-thumbnail.png
d7fb4e6efe97652bd06b1c42df316c7f
MD5
6
false
TEXT
Kuehn et al.pdf.txt
Kuehn et al.pdf.txt
Extracted text
text/plain
80699
https://repository.helmholtz-hzi.de/bitstream/10033/623068/4/Kuehn%20et%20al.pdf.txt
6d8ffb0a86cc12547b5d48d25ffc9364
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623068/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623068/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Kuehn et al.pdf
Kuehn et al.pdf
submitted manuscript
application/pdf
16715291
https://repository.helmholtz-hzi.de/bitstream/10033/623068/1/Kuehn%20et%20al.pdf
d67ec75281da8971d067de49b072d20c
MD5
1
true
10033/623068
oai:repository.helmholtz-hzi.de:10033/623068
2021-10-09 01:59:22.881
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6231182021-12-14T03:20:36Zcom_10033_128109com_10033_620659col_10033_621771col_10033_128110col_10033_620660
Formaglio, Pauline
9b9651ac87cc9cfd1fc2bf71f6a51a89
500
Alabdullah, Mohamad
e032ce68271015f38ebd0d9a3725b058
300
Siokis, Anastasios
a874c68d3386019489682d501c19027a
500
Handschuh, Juliane
cd91999dcee2e5e282afcf78d59269b1
500
Sauerland, Ina
4bc2c5dcf12c3fcc0408a33ca3723617
500
Fu, Yan
e3e0094b935718b415cb79a5a867e0ea
500
Krone, Anna
e5b13b4a360797e8098796e3f3af7310
500
Gintschel, Patricia
8904ec78b45c88551b23cd760ded22bd
500
Stettin, Juliane
51980311ba9aa7a9811ddb41a0964008
500
Heyde, Sandrina
230e493659ff5120a859da85d3efb073
500
Mohr, Juliane
7725bfc9c825244f563f140c649f33fe
500
Philipsen, Lars
5d7150da6a8ed2d5d9cce132f123f373
500
Schröder, Anja
17c73b229a8c34a0774eb9af3debfea6
300
Robert, Philippe A
b943b7622feddf538cc52c707cf425b5
500
Zhao, Gang
37ec65924f58972f17d1469d470e37d8
500
Khailaie, Sahamoddin
8253183c778cac6ad5456a4b21bf174a
500
Dudeck, Anne
613eb10be0e5b33cc7899254c13e4e4b
500
Bertrand, Jessica
887df5836ad01a93b2f5f3ab62773003
500
Späth, Gerald F
2515f8ad2f621c9e31d02d467fba6e14
300
Kahlfuß, Sascha
f726ed420e77fbd9522eaf944868ca53
300
Bousso, Philippe
ee6a0ac5915ea4fa3ecde01cbae3e2e9
500
Schraven, Burkhart
732f0e20e2b7411a1d421c8cfd71d687
500
Huehn, Jochen
81855dd40035a02edad8ee83ce210282
500
Binder, Sebastian
cd17c497203cd901f428297003a48de7
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Müller, Andreas J
541c2907891a6a8e749193dd768c4c15
500
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2021-12-13T14:09:55Z
2021-12-13T14:09:55Z
2021-10-15
mmunity. 2021 Oct 15:S1074-7613(21)00406-4. doi: 10.1016/j.immuni.2021.09.021. Epub ahead of print.
34687607
10.1016/j.immuni.2021.09.021
http://hdl.handle.net/10033/623118
1097-4180
Immunity
Nitric oxide (NO) is an important antimicrobial effector but also prevents unnecessary tissue damage by shutting down the recruitment of monocyte-derived phagocytes. Intracellular pathogens such as Leishmania major can hijack these cells as a niche for replication. Thus, NO might exert containment by restricting the availability of the cellular niche required for efficient pathogen proliferation. However, such indirect modes of action remain to be established. By combining mathematical modeling with intravital 2-photon biosensors of pathogen viability and proliferation, we show that low L. major proliferation results not from direct NO impact on the pathogen but from reduced availability of proliferation-permissive host cells. Although inhibiting NO production increases recruitment of these cells, and thus pathogen proliferation, blocking cell recruitment uncouples the NO effect from pathogen proliferation. Therefore, NO fulfills two distinct functions for L. major containment: permitting direct killing and restricting the supply of proliferation-permissive host cells.
en
Cell Press
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
2-photon microscopy
Leishmania
biosensor
iNOS
inflammation
intracellular pathogen
monocyte
nitric oxide
phagocyte
Nitric oxide controls proliferation of Leishmania major by inhibiting the recruitment of permissive host cells.
Article
Immunity
United States
2021-12-13T14:09:55Z
THUMBNAIL
Formaglio et al.pdf.jpg
Formaglio et al.pdf.jpg
Generated Thumbnail
image/jpeg
98103
https://repository.helmholtz-hzi.de/bitstream/10033/623118/5/Formaglio%20et%20al.pdf.jpg
9e89040b7c699d3a2c10a0f085cb83ae
MD5
5
false
TEXT
Formaglio et al.pdf.txt
Formaglio et al.pdf.txt
Extracted text
text/plain
157912
https://repository.helmholtz-hzi.de/bitstream/10033/623118/4/Formaglio%20et%20al.pdf.txt
0d3fe41d1d512469e203dfa3916a6fbb
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623118/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623118/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Formaglio et al.pdf
Formaglio et al.pdf
Open Access article
application/pdf
10337977
https://repository.helmholtz-hzi.de/bitstream/10033/623118/1/Formaglio%20et%20al.pdf
546ea9ff12990cefdfc45e32ad328c96
MD5
1
true
10033/623118
oai:repository.helmholtz-hzi.de:10033/623118
2021-12-14 03:20:36.909
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6231292022-01-07T01:48:30Zcom_10033_620659col_10033_620660
Knabl, Ludwig
0f6f84acbde976da788f973e2255f208
300
Mitra, Tanmay
956bf08ca9fa09db5ec611d4ea747195
500
Kimpel, Janine
ab9d2ca49c539df253491a109da1cf03
300
Rössler, Annika
935a587972e9c04bd2013f2492db5fa6
300
Volland, André
6efc7151eb7bbf24d4fafc30dc7a3ba1
300
Walser, Andreas
e46cafab895c786c8b42f68d8ad67b5b
300
Ulmer, Hanno
c64845923091b3263adc7051b8e4cbe3
300
Pipperger, Lisa
3809755a21ee8d583a12da4b6ee25bb6
300
Binder, Sebastian C
ca9fc32341dea761712a6ca7f0d7308b
600
http://orcid.org/0000-0003-1169-1786
Riepler, Lydia
a04e065e905c15536d3d50567384446f
300
Bates, Katie
3d9b95827f860fffbab022c62898f27c
300
Bandyopadhyay, Arnab
4746ea0b3b751fb8843b91e75579dbc5
500
Schips, Marta
74cbcb8b7d11f133b755b8597dd2f438
500
Ranjan, Mrinalini
fa5b036712b8eb2a11c8e7e93855fc65
300
Falkensammer, Barbara
3b112f5c0ef42af01c7e10ed48b0c853
300
Borena, Wegene
669577d0a45597ed898bceeba47a7a8c
300
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
von Laer, Dorothee
391bb85df621b4b33c021ca1d3f082b4
300
BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany.
2022-01-06T17:06:42Z
2022-01-06T17:06:42Z
2021-06-30
Commun Med (London). 2021;1(1):4. doi: 10.1038/s43856-021-00007-1. Epub 2021 Jun
34870284
10.1038/s43856-021-00007-1
http://hdl.handle.net/10033/623129
2730-664X
Communications medicine
Between April 21st and 27th 2020, a cross-sectional epidemiologic study targeting the full population of Ischgl (n = 1867), of which 79% could be included (n = 1473, incl. 214 children), was performed. For each individual, the study involved a SARS-CoV-2 PCR, antibody testing and structured questionnaires. A mathematical model was used to help understand the influence of the determined seroprevalence on virus transmission.
en
NPG
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
SARS virus
Viral epidemiology
Viral infection
High SARS-CoV-2 seroprevalence in children and adults in the Austrian ski resort of Ischgl.
Article
1
1
4
Communications medicine
England
2022-01-06T17:06:42Z
THUMBNAIL
Knabl et al.pdf.jpg
Knabl et al.pdf.jpg
Generated Thumbnail
image/jpeg
97496
https://repository.helmholtz-hzi.de/bitstream/10033/623129/5/Knabl%20et%20al.pdf.jpg
174c5722f269a2568b29327dcc5c9e35
MD5
5
false
TEXT
Knabl et al.pdf.txt
Knabl et al.pdf.txt
Extracted text
text/plain
49637
https://repository.helmholtz-hzi.de/bitstream/10033/623129/4/Knabl%20et%20al.pdf.txt
14ec1ed027d6ca0969bb5bce6998f379
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623129/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623129/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Knabl et al.pdf
Knabl et al.pdf
Open Access publication
application/pdf
1536985
https://repository.helmholtz-hzi.de/bitstream/10033/623129/1/Knabl%20et%20al.pdf
fd946c24b31de220e0fe630f2dc8d9fc
MD5
1
true
10033/623129
oai:repository.helmholtz-hzi.de:10033/623129
2022-01-07 01:48:30.682
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6232062022-06-14T01:57:09Zcom_10033_620659col_10033_620660
Mascheroni, Pietro
f046cc349bd1d2fe247ffdccdb2b8d21
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
2022-06-13T09:23:31Z
2022-06-13T09:23:31Z
2020-06-04
2020-02-21
1664-302X
32582070
10.3389/fmicb.2020.01083
http://hdl.handle.net/10033/623206
Frontiers in microbiology
Tumor-targeting bacteria elicit anticancer effects by infiltrating hypoxic regions, releasing
toxic agents and inducing immune responses. Although current research has largely
focused on the influence of chemical and immunological aspects on the mechanisms
of bacterial therapy, the impact of physical effects is still elusive. Here, we propose a
mathematical model for the anti-tumor activity of bacteria in avascular tumors that takes
into account the relevant chemo-mechanical effects. We consider a time-dependent
administration of bacteria and analyze the impact of bacterial chemotaxis and killing rate.
We show that active bacterial migration toward tumor hypoxic regions provides optimal
infiltration and that high killing rates combined with high chemotactic values provide the
smallest tumor volumes at the end of the treatment.We highlight the emergence of steady
states in which a small population of bacteria is able to constrain tumor growth. Finally,
we show that bacteria treatment works best in the case of tumors with high cellular
proliferation and low oxygen consumption.
en
Frontiers
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
bacterial therapy
cancer
chemotaxis
mathematical modeling
space competition
Investigating the Physical Effects in Bacterial Therapies for Avascular Tumors.
Article
11
1083
Frontiers in microbiology
Switzerland
2022-06-13T09:23:32Z
THUMBNAIL
MascheroniFrontiersMicrobiol2020.pdf.jpg
MascheroniFrontiersMicrobiol2020.pdf.jpg
Generated Thumbnail
image/jpeg
125491
https://repository.helmholtz-hzi.de/bitstream/10033/623206/5/MascheroniFrontiersMicrobiol2020.pdf.jpg
271f55c9d99de2cd78342e6b84586e1b
MD5
5
false
TEXT
MascheroniFrontiersMicrobiol2020.pdf.txt
MascheroniFrontiersMicrobiol2020.pdf.txt
Extracted text
text/plain
50433
https://repository.helmholtz-hzi.de/bitstream/10033/623206/4/MascheroniFrontiersMicrobiol2020.pdf.txt
a9eee02c7c0966d80d5361ae480e6d31
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623206/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623206/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
MascheroniFrontiersMicrobiol2020.pdf
MascheroniFrontiersMicrobiol2020.pdf
application/pdf
1541571
https://repository.helmholtz-hzi.de/bitstream/10033/623206/1/MascheroniFrontiersMicrobiol2020.pdf
764e889114bea7aa50359c6a1b4a55b8
MD5
1
true
10033/623206
oai:repository.helmholtz-hzi.de:10033/623206
2022-06-14 01:57:09.777
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6232232022-06-15T02:53:16Zcom_10033_620659col_10033_620660
Freudenhammer, Mirjam
0a3c79c1d855bacba297565be0aae094
300
Voll, Reinhard E
506ba8bed17a2ab8df5d0abe6cf7c74c
300
Binder, Sebastian C
5f59b1f232c7fd9dd584163b14e1b927
500
Keller, Baerbel
e792c0d8154f73bd116fa83ee54bcb9f
500
Warnatz, Klaus
5588a200294442ee7378e34913143797
500
2022-06-14T09:15:04Z
2022-06-14T09:15:04Z
2020-09-09
2020-03-30
32907998
10.4049/jimmunol.2000343
http://hdl.handle.net/10033/623223
1550-6606
Journal of immunology (Baltimore, Md. : 1950)
An expansion of CD21low B cells has been described in a variety of diseases associated with persistent immune stimulation as in chronic infection, immunodeficiency, or autoimmunity. Different developmental stages of CD21low B cells have been highlighted in specific diseases; however, a systematic comparison of distribution, phenotype, and signaling capacity of these populations has not yet been performed to delineate the pivotal character of this unusual B cell population. Screening of more than 200 patients with autoimmune disease demonstrated that the prevalence of patients with expanded CD21low B cells varies between diseases. The expansion was frequent in patients with systemic lupus erythematosus, in which it correlated to relative B cell lymphopenia and duration of disease. Different proportions of distinct developmental stages of CD21low B cells co-occur in nearly all patients with autoimmune disease. Although in most patients, naive-like and CD27- switched memory B cells were the most prominent CD21low subpopulations, there was no detectable association of the pattern with the underlying disease. Despite their distinct developmental stage, all CD21low B cells share a common core phenotype including the increased expression of inhibitory receptors, associated with an elevated constitutive phosphorylation of proximal signaling molecules downstream of the BCR but impaired Ca2+ mobilization and NF-κB activation after BCR stimulation. Further, this was accompanied by impaired upregulation of CD69, although CD86 upregulation was preserved. Beyond maturation-associated differences, the common core characteristics of all CD21low B cell populations suggests either a common ancestry or a shared sustained imprint by the environment they originated in.
en
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Naive- and Memory-like CD21 B Cell Subsets Share Core Phenotypic and Signaling Characteristics in Systemic Autoimmune Disorders.
Article
205
8
2016
2025
Journal of immunology (Baltimore, Md. : 1950)
United States
2022-06-14T09:15:05Z
THUMBNAIL
FreudenhammerJImmunol2020.pdf.jpg
FreudenhammerJImmunol2020.pdf.jpg
Generated Thumbnail
image/jpeg
85428
https://repository.helmholtz-hzi.de/bitstream/10033/623223/5/FreudenhammerJImmunol2020.pdf.jpg
e811fdf9ac87797d8e130e17441549b0
MD5
5
false
TEXT
FreudenhammerJImmunol2020.pdf.txt
FreudenhammerJImmunol2020.pdf.txt
Extracted text
text/plain
55440
https://repository.helmholtz-hzi.de/bitstream/10033/623223/4/FreudenhammerJImmunol2020.pdf.txt
cdf18f6a59ac3771c46fd00405fe7f8a
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623223/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623223/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
FreudenhammerJImmunol2020.pdf
FreudenhammerJImmunol2020.pdf
application/pdf
2576844
https://repository.helmholtz-hzi.de/bitstream/10033/623223/1/FreudenhammerJImmunol2020.pdf
9268b3e044e55aadd8df7997d6d8d65b
MD5
1
true
10033/623223
oai:repository.helmholtz-hzi.de:10033/623223
2022-06-15 02:53:16.831
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6232262022-06-15T02:52:29Zcom_10033_620659col_10033_620660
Montaseri, Ghazal
0188311a96861e58b03f0dde1e12040f
500
Alfonso, Juan Carlos López
111f7079156479cfa5feaa2c5d6e1be7
500
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
2022-06-14T13:44:32Z
2022-06-14T13:44:32Z
2020-02-07
2019-05-22
31790681
10.1016/j.jtbi.2019.110099
http://hdl.handle.net/10033/623226
1095-8541
Journal of theoretical biology
en
Elsevier
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
A minimal modeling framework of radiation and immune system synergy to assist radiotherapy planning.
Article
486
110099
Journal of theoretical biology
England
2022-06-14T13:44:33Z
THUMBNAIL
MontaseriJTheoretBiol2020.pdf.jpg
MontaseriJTheoretBiol2020.pdf.jpg
Generated Thumbnail
image/jpeg
74101
https://repository.helmholtz-hzi.de/bitstream/10033/623226/5/MontaseriJTheoretBiol2020.pdf.jpg
7fb3c997d1e54fe4742422234c5b90bf
MD5
5
false
TEXT
MontaseriJTheoretBiol2020.pdf.txt
MontaseriJTheoretBiol2020.pdf.txt
Extracted text
text/plain
67269
https://repository.helmholtz-hzi.de/bitstream/10033/623226/4/MontaseriJTheoretBiol2020.pdf.txt
2de89f5c0f0393a3a032ad834ede08fc
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623226/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623226/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
MontaseriJTheoretBiol2020.pdf
MontaseriJTheoretBiol2020.pdf
application/pdf
1606764
https://repository.helmholtz-hzi.de/bitstream/10033/623226/1/MontaseriJTheoretBiol2020.pdf
91c3b1c72b6853441289b0de53c4d903
MD5
1
true
10033/623226
oai:repository.helmholtz-hzi.de:10033/623226
2022-06-15 02:52:29.147
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6232382022-08-11T01:55:06Zcom_10033_620659col_10033_620660
Demetriou, Philippos
e94c818d5e6829a63beddc6a29d2176e
500
Abu-Shah, Enas
3f43c205c0764d55060c10671c7ffe7f
300
Valvo, Salvatore
bb09b705f51a82b80c2ba3d8da901dc7
300
McCuaig, Sarah
8ac6324fd7ba7aa268f42809cf05f755
300
Mayya, Viveka
5d4cd0faedc31f7b23ed79ba539408d7
300
Kvalvaag, Audun
6fac01db255e5ac8beb45b64315839f0
300
Starkey, Thomas
493962acc39b70c173a7069933633a66
300
Korobchevskaya, Kseniya
2ef1ae0b3707dcf21db58e488bddbcc2
300
Lee, Lennard Y W
35ad51e9f80bc982557be39f838b038d
300
Friedrich, Matthias
681c2fc893a699f48b2239fcfdc0ad9d
300
Mann, Elizabeth
fc7889c50511f00ee6fa3c613c884776
300
Kutuzov, Mikhail A
b134947f76d1d8ae8e0f9eaff129c3ef
300
Morotti, Matteo
b8b6336308ae265ff9e3e2a017d30ad0
300
Wietek, Nina
5e1e1d85293b4dc5344a438c876e2ba8
300
Rada, Heather
0018ab83347cb15ee3b4cdd611a00252
300
Yusuf, Shamsideen
bf0c8460939462bd3530f8696d5e2a8f
300
Afrose, Jehan
827be50031d63720142a5b3f7e1de998
300
Siokis, Anastasios
a874c68d3386019489682d501c19027a
500
Meyer-Hermann, Michael
f054b81293a071d59f3be787198a3299
Ahmed, Ahmed Ashour
97ed99dba03a1994f7a08fce70c92229
Depoil, David
8d626f82c12b6a418355081edc9fa14e
300
Dustin, Michael L
ac13dfbdd962c435ae8154c76ebb5bd1
500
2022-08-10T08:40:34Z
2022-08-10T08:40:34Z
2020-09-14
32929275
10.1038/s41590-020-0770-x
http://hdl.handle.net/10033/623238
1529-2916
Nature immunology
The CD2-CD58 recognition system promotes adhesion and signaling and counters exhaustion in human T cells. We found that CD2 localized to the outer edge of the mature immunological synapse, with cellular or artificial APC, in a pattern we refer to as a 'CD2 corolla'. The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators. The corolla amplified active phosphorylated Src-family kinases (pSFK), LAT and PLC-γ over T cell receptor (TCR) alone. CD2-CD58 interactions in the corolla boosted signaling by 77% as compared with central CD2-CD58 interactions. Engaged PD-1 invaded the CD2 corolla and buffered CD2-mediated amplification of TCR signaling. CD2 numbers and motifs in its cytoplasmic tail controlled corolla formation. CD8+ tumor-infiltrating lymphocytes displayed low expression of CD2 in the majority of people with colorectal, endometrial or ovarian cancer. CD2 downregulation may attenuate antitumor T cell responses, with implications for checkpoint immunotherapies.
en
Attribution-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-sa/4.0/
A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals.
Article
21
10
1232
1243
Nature immunology
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United States
2022-08-10T08:40:34Z
THUMBNAIL
s41590-020-0770-x(1).pdf.jpg
s41590-020-0770-x(1).pdf.jpg
Generated Thumbnail
image/jpeg
133947
https://repository.helmholtz-hzi.de/bitstream/10033/623238/5/s41590-020-0770-x%281%29.pdf.jpg
9c97db0cf853a8c2c390748d8f4cfa43
MD5
5
false
TEXT
s41590-020-0770-x(1).pdf.txt
s41590-020-0770-x(1).pdf.txt
Extracted text
text/plain
101149
https://repository.helmholtz-hzi.de/bitstream/10033/623238/4/s41590-020-0770-x%281%29.pdf.txt
8697be91f94f266868a65c32b6238050
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623238/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
1025
https://repository.helmholtz-hzi.de/bitstream/10033/623238/2/license_rdf
84a900c9dd4b2a10095a94649e1ce116
MD5
2
false
ORIGINAL
s41590-020-0770-x(1).pdf
s41590-020-0770-x(1).pdf
application/pdf
7745272
https://repository.helmholtz-hzi.de/bitstream/10033/623238/1/s41590-020-0770-x%281%29.pdf
1e3788e85f9c200277b321d3d3c55b1e
MD5
1
true
10033/623238
oai:repository.helmholtz-hzi.de:10033/623238
2022-08-11 01:55:06.575
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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
oai:repository.helmholtz-hzi.de:10033/6232432022-08-11T01:54:35Zcom_10033_620659col_10033_620660
Nava-Sedeño, Josué Manik
05c2bc5eb62c5716e7d656f3a90ad617
300
Voß-Böhme, Anja
53c2facf9de359df1245eed0ec8a0a92
300
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Deutsch, Andreas
5d5b35cc14130c278f0f88d48746681b
500
Peruani, Fernando
0964c7c39e8f855c526ebf2cea3e906e
300
2022-08-10T09:48:51Z
2022-08-10T09:48:51Z
2020-07-27
32713300
10.1098/rstb.2019.0378
http://hdl.handle.net/10033/623243
1471-2970
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
en
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
alignment interactions
cellular automata
collective motion
off-lattice model
on-lattice model
Modelling collective cell motion: are on- and off-lattice models equivalent?
Review
375
1807
20190378
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
England
2022-08-10T09:48:51Z
THUMBNAIL
Nava-Sedeno.pdf.jpg
Nava-Sedeno.pdf.jpg
Generated Thumbnail
image/jpeg
125792
https://repository.helmholtz-hzi.de/bitstream/10033/623243/5/Nava-Sedeno.pdf.jpg
461725e1623a24d69c222194295e4bd9
MD5
5
false
TEXT
Nava-Sedeno.pdf.txt
Nava-Sedeno.pdf.txt
Extracted text
text/plain
45790
https://repository.helmholtz-hzi.de/bitstream/10033/623243/4/Nava-Sedeno.pdf.txt
a7dffee78f5abadd11f108dc4c04caae
MD5
4
false
LICENSE
license.txt
license.txt
text/plain
1685
https://repository.helmholtz-hzi.de/bitstream/10033/623243/3/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
3
false
CC-LICENSE
license_rdf
license_rdf
application/rdf+xml; charset=utf-8
908
https://repository.helmholtz-hzi.de/bitstream/10033/623243/2/license_rdf
0175ea4a2d4caec4bbcc37e300941108
MD5
2
false
ORIGINAL
Nava-Sedeno.pdf
Nava-Sedeno.pdf
application/pdf
964182
https://repository.helmholtz-hzi.de/bitstream/10033/623243/1/Nava-Sedeno.pdf
030204f381c107883befbfabb5fa7eec
MD5
1
true
10033/623243
oai:repository.helmholtz-hzi.de:10033/623243
2022-08-11 01:54:35.373
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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