BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509020000?filename=MODEL1509020000.pdfhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509020000?filename=MODEL1509020000_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509020000?filename=MODEL1509020000_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509020000?filename=MODEL1509020000.scihttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509020000?filename=MODEL1509020000.pnghttps://www.ebi.ac.uk/biomodels/model/download/MODEL1509020000?filename=MODEL1509020000.vcmlprimaryOK200James BoydNon-curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/MODEL150902000019359585falseBioModelsSBMLModelsAshall2009 NFkappaB dependent transcription2009MODEL1509020000Louise Ashall, Caroline A Horton, D E Nelson, Pawel Paszek, Claire V Harper, Kate Sillitoe, Sheila Ryan, David G Spiller, John F Unitt, David S Broomhead, D B Kell, David A Rand, Violaine Sée, Michael R H WhiteLouise Ashall19359585, The nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappaB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappaB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.. 5924, 324. Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Crown Street, Liverpool, L69 7ZB, UK.james.boyd@manchester.ac.ukUniversity of ManchesterThe nuclear factor kappaB (NF-kappaB) transcription factor regulates cellular stress responses and the immune response to infection. NF-kappaB activation results in oscillations in nuclear NF-kappaB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor-alpha at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-kappaB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-kappaB-dependent gene expression, which supports the idea that oscillation frequency has a functional role.Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription.Ashall Louise L, Horton Caroline A CA, Nelson David E DE, Paszek Pawel P, Harper Claire V CV, Sillitoe Kate K, Ryan Sheila S, Spiller David G DG, Unitt John F JF, Broomhead David S DS, Kell Douglas B DB, Rand David A DA, Sée Violaine V, White Michael R H MRDmelCG6667, DL, ird4, DmelCG11992, l(3)neo36, NF-kappaB, p50, Dorsal, fs(2)k10816, NFKB-p50, NF-kB1, relish, bacterial transcription., RELI, GSd447, rel, Rel-p110, ird, EBP-1, NF-kappa-B, KBF1, mat(2)dorsal, d, Dor, Dl, dL, NFKB-p105, anon-EST:GressD7, CG6667, p105, REL, transcription from bacterial-type RNA polymerase promoter, Rel/NF-kappaB, CG11992, NFkappaBImmunoglobulin Enhancer-Binding Protein, T-cell leukemia, TNF-alpha, Tumor Necrosis Factor Ligand Superfamily Member 2, NF-kB, ird4, kappa B Enhancer Binding Protein, NF-kappaB, p50, Immunoglobulin, watermelon stomach, P62, NFKB-p50, relish, AGL4, Infestations and Infections, Gene, Cachectin Tumor Necrosis Factor, SEPALLATA 2, disfunctional, sci, Transcription Factor, Ig EBP 1, NF-kappaB activation, Enhancer-Binding Protein, zinc ion regulated core promoter proximal region sequence-specific DNA binding, GAVE, reduced, Roles, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, NF-KB1, HOW, How, Concepts, activation of NF-kappaB, nuclear translocation, Nuclear Factor kappa B, tiny, Role Concepts., Watermelon stomach (disorder), l(3)j5D5, CG11992, Pulses, Tumor Necrosis Factor, Transcription Factor NF-kB, 24B, Transcription, Immune Processes, Immune Responses, anatomical systems, l(3)s2612, Gene Expressions, Cachectin-Tumor Necrosis Factor, occurrence, NF-kB1, Complex, prevalence, hypoplasia, stru, NF-kappa B, F10N7_150, stubby, l(3)S053606, ird, Nuclear Factor Kappab, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, clinical infection, CG10293, Expressions, TNF Superfamily, Nuclear Factor-Kappab, KBF1, l(3)j5B5, Infestation and Infection, Ig-EBP-1, Immune Response, Immune, Member 2, RNA polymerase II proximal promoter sequence-specific DNA binding, copper ion regulated proximal promoter sequence-specific DNA binding, NF-kappaB1, activation of NF-kappaB transcription factor, heterogeneity, DmelCG10293, AGAMOUS-like 4, zinc ion regulated proximal promoter sequence-specific DNA binding, tumor necrosis factor, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, Infections and Infestations, Expression, Factor-Kappab, REL, TL, Immune Process, Immunoglobulin Enhancer Binding Protein, TRANSCRIPTION FACTOR, incidence, RNA polymerase II distal enhancer sequence-specific binding, small, gastric antral vascular ectasia (disorder), RNA polymerase II core promoter proximal region sequence-specific binding, 0904/17, Gastric Antral Vascular Ectasia, l(3)neo36, Process, functional failure, clone 2.39, Tumor Necrosis Factor alpha, frequency, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, Factor, function, defective, rel, qkr, Rel-p110, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, l(3)S090417, results, Cell, predicted, Concept, transcription factor activity, shortened, Role Concept, Factor NF-kB, NFKB-p105, SZ1, nuclear import, KH93F, Infection, Role, RNA polymerase II transcription factor activity, Nuclear, p105, Transcription Factor NF kB, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, failure, gastric antral vascular ectasia, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, KNOTTED1-like homeobox gene 5, outbreaks, NFkappaB, who, F14P3.4, Cachectin, Factors, DmelCG11992, p50|p105, underdeveloped, F14P3_4, Infection and Infestation, RELI, TNFalpha, Who/How, metal ion regulated core promoter proximal region sequence-specific binding, copper ion regulated core promoter proximal region sequence-specific binding, NF-kappa B Complex, surveillance, EBP-1, Transcription factor, morbidity, F10N7.150, endemics, NF kappa B Complex, NF-kappa-B, NF kappaB, p50/p105, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Response, qkr[93F], epidemics, anon-EST:Liang-2.39, NF kB, Feedbacks, short, Rel/NF-kappaB, metal ion regulated sequence-specific DNA binding, metal ion regulated proximal promoter sequence-specific DNA bindingGpi, phapii, Therapy, IPP2A2, AI461847, AW413978, igaad, StF-IT-1, white, Pulses., MF, compositionality, Amf, composed of, PHAPII, group, 5730420M11Rik, mOC-X, Caucasian, Abc8, I-2PP2A, European, Dm I-2, I2PP2A, Pgi, NK|GPI, Gpi-1, Caucasoid, NK, Caucasians, treatment, SET, Org, ORG, Occidental, HLA-DR-associated protein II, ensemble, DI-2, TAF-I, Gpi-1r, Nlk, Gpi-1s, content, long, I-2Dm, Phi, ipp2a2, Gpi-1t, Gpi1-r, 2pp2a, Sciences, Gpi1-s, composition, CG4299, Gpi1-t, Treatments, CG10574, DmelCG4299, I-2PP1, IGAAD, set, dSET/TAF-Ibeta, 2610030F17Rik, TAF-IBETA, 2PP2A, DmelCG10574, Therapeutic, Whites, taf-ibeta, structure, disease management, dSET, dSet, Therapies, White, Treatment, TAF-Ibeta, AA407739, i2pp2a, Bglap-rs1, Gpi1s, NK/GPIImmunoglobulin Enhancer-Binding Protein, NF-kB, ird4, kappa B Enhancer Binding Protein, l(3)neo36, NF-kappaB, p50, Immunoglobulin, NFKB-p50, relish, bacterial transcription., rel, Rel-p110, Transcription Factor, Ig EBP 1, Enhancer-Binding Protein, Factor NF-kB, NFKB-p105, NF-KB1, Nuclear, p105, Transcription Factor NF kB, Nuclear Factor kappa B, CG11992, NFkappaB, Transcription Factor NF-kB, Transcription, DmelCG11992, p50|p105, NF-kB1, Complex, NF-kappa B, RELI, ird, NF-kappa B Complex, Nuclear Factor Kappab, EBP-1, Nuclear Factor-Kappab, NF kappa B Complex, NF-kappa-B, KBF1, Ig-EBP-1, NF kappaB, p50/p105, NF-kappaB1, NF kB, Factor-Kappab, REL, transcription from bacterial-type RNA polymerase promoter, Rel/NF-kappaB, Immunoglobulin Enhancer Binding ProteinfalseAshall2009 - NFkappaB dependent transcription Model taken from Ashall et al., Science, 2009 (http://www.sciencemag.org/content/324/5924/242.long). Contact: mike.white@manchester.ac.uk. Simulation set for continuous treatment. For pulsing treatment, set 'pulse_b' events to zero. 2016-02-102016-02-102015-09-02MODEL150902000019359585MODEL1509020000