Stochastic regulation of the Interleukin-4 gene: short-term memory in Th2 differentiation
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
Berlin
Logos Verl.
2011
|
| Subjects: | |
| Online Access: | Inhaltstext Inhaltsverzeichnis |
| Physical Description: | VIII, 166 S. Ill., graph. Darst. |
| ISBN: | 9783832530037 3832530037 |
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| 245 | 1 | 0 | |a Stochastic regulation of the Interleukin-4 gene |b short-term memory in Th2 differentiation |c Luca Mariani |
| 264 | 1 | |a Berlin |b Logos Verl. |c 2011 | |
| 300 | |a VIII, 166 S. |b Ill., graph. Darst. | ||
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| 502 | |a Zugl.: Berlin, Humboldt-Univ., Diss., 2010 | ||
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Record in the Search Index
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| adam_text |
IMAGE 1
C O N T E N T S
1 INTRODUCTION 1
1.1 FUNCTION, REGULATION A N D VARIABILITY OF CYTOKINE GENES 2
1.2 REGULATION OF T H CELLS DIFFERENTIATION 3
1.3 REGULATION OF IL-4 EXPRESSION 8
1.3.1 EPIGENETIC REGULATION OF T H 2 DIFFERENTIATION A N D IL-4
EXPRESSION 9 1.3.2 MONOALLELIC EXPRESSION A N D PROBABILISTIC REGULATION
. . . . . 10
1.3.3 TRANSCRIPTION FACTORS IN IL-4 REGULATION: NFAT1, GATA-3 A N D
STATG 12
1.4 VARIABILITY IN GENE EXPRESSION 14
1.4.1 ORIGINS A N D COMPONENTS OF T H E VARIABILITY 15
1.4.2 GRADED A N D BINARY REGULATION 18
1.5 RESEARCH AIMS 18
2 STOCHASTIC MODELS O F GENE EXPRESSION 2 3
2.1 STOCHASTIC MODEL OF M R N A PRODUCTION/DEGRADATION 24
2.1.1 MULTIPLE PRODUCTION OF MRNAS: BURST-LIKE TRANSCRIPTION . . 27 2.2
STOCHASTIC MODEL OF PROTEIN PRODUCTION/DEGRADATION 28
2.2.1 MULTIPLE DEGRADATION OF PROTEINS: VESICLE SECRETION 29
2.2.2 MULTIPLE PRODUCTION/DEGRADATION 31
2.3 COUPLING TRANSCRIPTION A N D TRANSLATION IN SINGLE GENE EXPRESSION .
. 31 2.3.1 MULTIPLE PRODUCTION/DEGRADATION OF M R N A S A N D PROTEINS .
35 2.4 GENE INDUCTION: GRADED A N D BINARY REGULATION 38
2.4.1 REGULATION MODES A T T H E M R N A LEVEL 39
2.4.2 REGULATION MODES A T T H E PROTEIN LEVEL 4 1
2.4.3 NOISE STRENGTH A N D SYSTEM MEMORY 43
2.5 DISCUSSION 45
3 STOCHASTIC FEATURES IN IL-4 EXPRESSION 4 7
3.1 KINETICS OF IL-4 ACTIVATION 48
3.2 GATA-3 HOMOGENEITY 51
3.3 ESTIMATION OF IL-4 EXPRESSION RATE CONSTANTS 51
3.4 POST-TRANSCRIPTIONAL VARIABILITY IN IL-4 GENE REGULATION 54
3.5 DISCUSSION 56
HTTP://D-NB.INFO/1023924838
IMAGE 2
I V
C O N T E N T S
4 STOCHASTIC M O D E L O F IL-4 INDUCTION DURING ANTIGEN STIMULATION 5 9
4.1 TWO-STEPS MODEL OF IL-4 INDUCTION 59
4.2 SIMULATIONS VS. STIMULATIONS 62
4.3 BEST-FITTING OF T H E D A T A 63
4.4 DISCUSSION 64
5 MODELING NFAT1 ACTIVATION DURING IL-4 INDUCTION 6 7
5.1 PHOSPORYLATION A N D TRANSLOCATION: SEQUENTIAL STEPS IN NFAT1 ACTI
VATION 69
5.2 REDUCED MODEL FOR STOCHASTIC IL-4 INDUCTION 71
5.3 EXPERIMENTS WITH NFAT1 INHIBITORS CONFIRM THE PREDICTIONS OF T H E
MODEL 74
5.4 DISCUSSION 76
6 IL-4 INDUCTION U P O N SECOND STIMULATION 7 9
6.1 SHORT-TERM MEMORY IN IL-4 ACTIVATION 79
6.2 FITTING T H E SECOND STIMULATION TO T H E MODEL 80
6.3 SHORT-TERM MEMORY IS INDEPENDENT FROM CELL-CYCLE 82
6.4 IL-4 EXPRESSING A N D NON-EXPRESSING CELLS DIFFER IN THEIR IL-4 RE
ACTIVATION PROBABILITY 82
6.5 SHORT-TERM MEMORY IS ALLELE-SPECIFIC A N D INDEPENDENT FROM G A T A
- 3 A N D FROM CELL-CYCLE 85
6.6 DISCUSSION 89
7 IL-4 EXPRESSION U P O N T H 2 DIFFERENTIATION 9 3
7.1 T H E INCREASE OF IL-4 COMPETENCE IN T H 2 CELL DIFFERENTIATION 93
7.2 DISCUSSION 98
8 A M O D E L FOR GATA-3 A N D T - B E T CROSS-INHIBITION 101
8.1 CROSS-IHNIBITION IN T H DIFFERENTIATION 101
8.2 A MATHEMATICAL MODEL FOR T H L - T H 2 CROSS-REGULATION 103
8.3 MODEL INTERPRETATION OF T H E ASYMMETRY IN T H REPROGRAMMING . . .
106
8.4 DISCUSSION 107
9 CONCLUSIONS 109
9.1 SUMMARY A N D DISCUSSION 109
9.2 FUTURE OUTLOOKS I L L
10 MATHEMATICAL A P P E N D I X 115
10.1 MARKOV PROCESSES 115
10.2 CHEMICAL MASTER EQUATION (CME) 116
10.3 PROBABILITY GENERATING FUNCTION ( P G F ) 117
10.4 TIME EVOLUTION OF T H E CENTRAL MOMENTS 118
10.5 GENERALIZATION FOR SYSTEM WITH MANY CHEMICAL COMPOUNDS 120
10.6 STOCHASTIC MODELS OF SINGLE GENE EXPRESSION 121
10.7 LANGEVIN APPROACH A N D AUTOCORRELATION FUNCTION 125
IMAGE 3
C O N T E N T S V
10.8 PROTEINS INHERITED BY T H E PROGENITOR ACTIVATION PHASE 127
11 STATISTICAL AND COMPUTATIONAL M E T H O D S 129
11.1 VARIABILITY A N D CORRELATION IN ALLELIC EXPRESSION 129
11.1.1 FLUORESCENCE INTENSITY, PROTEIN NUMBER A N D BACKGROUND . . 129
11.1.2 STATISTICAL PROPERTIES OF THE ALLELIC CORRELATION 129
11.1.3 D A T A ANALYSIS 132
11.2 TRANSCRIPTION FACTOR ACTIVITY A N D OCCUPANCY OF T H E BINDING
SITE. . 132 11.3 GILLESPIE ALGORITHM FOR THE C M E SOLUTION 133
11.4 SIMULATED ANNEALING FOR GLOBAL MINIMA 134
11.5 PROFILE-LIKELIHOOD-BASED M E T H O D FOR CONFIDENCE INTERVALS 136
11.5.1 LIKELIHOOD PROPERTIES 136
11.5.2 LIKELIHOOD IN BEST-FITTING 137
11.5.3 PROFILE-LIKELIHOOD-BASED M E T H O D 137
12 EXPERIMENTAL MATERIAL AND M E T H O D S 139
12.1 T H 2 CELL CULTURES 139
12.1.1 NAIVE T H CELL SORTING 139
12.1.2 T H 2 CELL PRIMING: OVA-APC STIMULATION 139
12.1.3 T H 2 CELL ACTIVATION: PMA-IONOMYCIN STIMULATION 139
12.1.4 IL-4 SECRETION ASSAY: ANTICD3-ANTICD28 STIMULATION . . . . 141
12.2 MEASUREMENTS OF IL-4 EXPRESSION IN T H 2 CULTURES 142
12.2.1 IL-4 INTRACELLULAR STAINING BY FACS A N D PROLIFERATION MARKER
LABELING 142
12.2.2 IL-4 EXTRACELLULAR ACCUMULATION BY ELISA 143
12.2.3 M R N A EXTRACTION A N D QUANTIFICATION BY REAL-TIME P C R . .
143 12.3 HELA CELLS CULTURES: QUANTIFICATION OF NFAT1 PHOSPHORYLATION A
N D TRANSLOCATION 143
ZUSAMMENFASSUNG 159
DANKSAGUNG 165
ERKLARUNG 167 |
| any_adam_object | 1 |
| author | Mariani, Luca 1977- |
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| author_sort | Mariani, Luca 1977- |
| author_variant | l m lm |
| building | Verbundindex |
| bvnumber | BV040361594 |
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| dewey-full | 571.966 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.966 |
| dewey-search | 571.966 |
| dewey-sort | 3571.966 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| illustrated | Illustrated |
| indexdate | 2024-08-21T00:05:34Z |
| institution | BVB |
| isbn | 9783832530037 3832530037 |
| language | English |
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| physical | VIII, 166 S. Ill., graph. Darst. |
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| publishDateSearch | 2011 |
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| publisher | Logos Verl. |
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| spelling | Mariani, Luca 1977- Verfasser (DE-588)1025047591 aut Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation Luca Mariani Berlin Logos Verl. 2011 VIII, 166 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zugl.: Berlin, Humboldt-Univ., Diss., 2010 Genregulation (DE-588)4122166-7 gnd rswk-swf Interleukin 4 (DE-588)4212826-2 gnd rswk-swf Helferzelle (DE-588)4258130-8 gnd rswk-swf Maus (DE-588)4169148-9 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Maus (DE-588)4169148-9 s Helferzelle (DE-588)4258130-8 s Interleukin 4 (DE-588)4212826-2 s Genregulation (DE-588)4122166-7 s DE-604 X:MVB text/html http://deposit.dnb.de/cgi-bin/dokserv?id=4070097&prov=M&dok_var=1&dok_ext=htm Inhaltstext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025215438&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Mariani, Luca 1977- Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation Genregulation (DE-588)4122166-7 gnd Interleukin 4 (DE-588)4212826-2 gnd Helferzelle (DE-588)4258130-8 gnd Maus (DE-588)4169148-9 gnd |
| subject_GND | (DE-588)4122166-7 (DE-588)4212826-2 (DE-588)4258130-8 (DE-588)4169148-9 (DE-588)4113937-9 |
| title | Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation |
| title_auth | Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation |
| title_exact_search | Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation |
| title_full | Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation Luca Mariani |
| title_fullStr | Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation Luca Mariani |
| title_full_unstemmed | Stochastic regulation of the Interleukin-4 gene short-term memory in Th2 differentiation Luca Mariani |
| title_short | Stochastic regulation of the Interleukin-4 gene |
| title_sort | stochastic regulation of the interleukin 4 gene short term memory in th2 differentiation |
| title_sub | short-term memory in Th2 differentiation |
| topic | Genregulation (DE-588)4122166-7 gnd Interleukin 4 (DE-588)4212826-2 gnd Helferzelle (DE-588)4258130-8 gnd Maus (DE-588)4169148-9 gnd |
| topic_facet | Genregulation Interleukin 4 Helferzelle Maus Hochschulschrift |
| url | http://deposit.dnb.de/cgi-bin/dokserv?id=4070097&prov=M&dok_var=1&dok_ext=htm http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025215438&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT marianiluca stochasticregulationoftheinterleukin4geneshorttermmemoryinth2differentiation |