Datasets:

bigbio

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bionlp_st_2013_ge

like 1

[ { "id": "PMC-2065877-17-Materials_and_Methods__text", "type": "abstract", "text": [ "Immunoblot analysis.\nWhole cell lysates were prepared in radioimmunoprecipitation assay (RIPA) buffer (20 mM Tris-HCl [pH 7.5], 150 mM NaCl, 1 mM EDTA, 1% NP-40, 0.1% SDS, 0.1% sodium deoxycholate) supplemented with 2 mM phenylmethylsulfonyl fluoride, 1 mM Na3VO4, and 1:100 protease/phosphatase inhibitor cocktails (Sigma). Crude lysates were centrifuged at 13,000 rpm for 10 min at 4 degreesC and the supernatants were collected for further analysis. Protein concentrations were determined with the Bio-Rad DC protein assay system. Lysates were boiled in the presence of 2.5% beta-mecaptoethanol, separated by denaturing SDS-PAGE, and transferred to 0.45-mum Optitran membranes (Schleicher & Schuell) in a Bio-Rad transfer unit. Membranes were immunoblotted with the appropriate primary antibody followed by horseradish peroxidase-tagged secondary antibodies (Amersham Biosciences and Dako) and detected with the SuperSignal West Pico System (Pierce)." ], "offsets": [ [ 0, 953 ] ] } ]

[ { "id": "PMC-2065877-17-Materials_and_Methods_T1", "type": "Protein", "text": [ "peroxidase" ], "offsets": [ [ 822, 832 ] ], "normalized": [] } ]

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[ { "id": "PMC-3279418-09-Materials_and_Methods__text", "type": "abstract", "text": [ "Mice\nSpecific-pathogen free colonies of C57BL/KaLawRij-Sharpincpdm/RijSunJ (JR#7599) and WT mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and were maintained in a barrier facility. Normal littermate controls were either +/+ or +/Sharpincpdm. These control animals were phenotypically indistinguishable and are referred to as WT. Sex-matched WT and mutant mice were used at 6-10 weeks of age. For some experiments, cpdm mice were crossed with transgenic mice with a bacterial artificial chromosome (BAC) containing the Sharpin gene (FVB/NJ-Tg(RP24-173I23)1Sun/Sun, JR#8279). These mice were backcrossed onto the C57BL/KaLawRij-Sharpincpdm/RijSunJ background and N4 mice were used in the experiments reported here. All mouse work was carried out in strict accordance with the approved protocols by the Institutional Animal Care and Use Committee." ], "offsets": [ [ 0, 862 ] ] } ]

[ { "id": "PMC-3279418-09-Materials_and_Methods_T1", "type": "Protein", "text": [ "Sharpin" ], "offsets": [ [ 536, 543 ] ], "normalized": [] } ]

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[ { "id": "PMC-2664230-09-RESULTS__text", "type": "abstract", "text": [ "The effects of PTX on LPS-induced TNF-alpha production\nTo determine the duration of PDE inhibition on TNF-alpha production after LPS stimulation, time course studies were conducted. In accordance with prior work, PTX had a rapid and sustained effect on TNF-alpha production in vitro (Figure 1)." ], "offsets": [ [ 0, 294 ] ] } ]

[ { "id": "PMC-2664230-09-RESULTS_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 34, 43 ] ], "normalized": [] }, { "id": "PMC-2664230-09-RESULTS_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 102, 111 ] ], "normalized": [] }, { "id": "PMC-2664230-09-RESULTS_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 253, 262 ] ], "normalized": [] } ]

[ { "id": "PMC-2664230-09-RESULTS_E1", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 4, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_E2" } ] }, { "id": "PMC-2664230-09-RESULTS_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 26, 33 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_E3" } ] }, { "id": "PMC-2664230-09-RESULTS_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 44, 54 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_T1" } ] }, { "id": "PMC-2664230-09-RESULTS_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 112, 122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_T2" } ] }, { "id": "PMC-2664230-09-RESULTS_E5", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 133, 144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_E4" } ] }, { "id": "PMC-2664230-09-RESULTS_E6", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 243, 249 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_E7" } ] }, { "id": "PMC-2664230-09-RESULTS_E7", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 263, 273 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-09-RESULTS_T3" } ] } ]

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[ { "id": "PMC-1447668-16-Materials_and_Methods__text", "type": "abstract", "text": [ "Real-time PCR.\nReal-time PCR analysis of HTLV-I (Tax) proviral load was performed as previously described [47,50]. DNA was extracted from 1 x 106 cells using Puregene DNA Isolation Kit (Gentra, Minneapolis, Minnesota, United States), and 100 ng of the sample DNA solution was analyzed by this system. The HTLV-I proviral DNA load was calculated by the following formula: copy number of HTLV-I (pX) per 100 cells = (copy number of pX)/(copy number of beta-actin/2) x 100." ], "offsets": [ [ 0, 470 ] ] } ]

[ { "id": "PMC-1447668-16-Materials_and_Methods_T1", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 49, 52 ] ], "normalized": [] }, { "id": "PMC-1447668-16-Materials_and_Methods_T2", "type": "Protein", "text": [ "beta-actin" ], "offsets": [ [ 450, 460 ] ], "normalized": [] } ]

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[ { "id": "PMC-2889865-21-Caption-Figure_5__text", "type": "abstract", "text": [ "Involvement of NF-kappaB in cytokine regulation. Cytokine/chemokine levels were determined using ELISA following incubation of Jurkat T-cells with NAI (1 h) and stimulation (24 h). (A) CXCL8 expression was partially inhibited following PMA stimulation (grey bars), whereas the levels were not altered following stimulation with HK E. coli (black bars), this indicates an induction mainly regulated by AP-1. (B) TNF expression was not affected by NAI. (C) IL-6 release was completely inhibited by NAI following PMA exposure, indicating regulation through NF-kappaB since IL-6 expression was significantly increased in response to HK E. coli than PMA. Statistical significance from the positive control (PMA/HK E. coli) was determined using Student's t-test. (n = 3)." ], "offsets": [ [ 0, 765 ] ] } ]

[ { "id": "PMC-2889865-21-Caption-Figure_5_T1", "type": "Protein", "text": [ "CXCL8" ], "offsets": [ [ 185, 190 ] ], "normalized": [] }, { "id": "PMC-2889865-21-Caption-Figure_5_T2", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 455, 459 ] ], "normalized": [] }, { "id": "PMC-2889865-21-Caption-Figure_5_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMC-2889865-21-Caption-Figure_5_T4", "type": "Anaphora", "text": [ "the levels" ], "offsets": [ [ 273, 283 ] ], "normalized": [] } ]

[ { "id": "PMC-2889865-21-Caption-Figure_5_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 191, 201 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_T1" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 216, 225 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E1" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E3", "type": "Regulation", "trigger": { "text": [ "altered" ], "offsets": [ [ 293, 300 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E1" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 371, 380 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E1" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E5", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 388, 397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E4" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E6", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 460, 467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_T2" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 483, 492 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E6" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 535, 545 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E6" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 575, 585 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_T3" } ] }, { "id": "PMC-2889865-21-Caption-Figure_5_E10", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 604, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2889865-21-Caption-Figure_5_E9" } ] } ]

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[ { "id": "PMC-3279418-24-Caption-Figure_6__text", "type": "abstract", "text": [ "Inhibition of NF-kappaB signaling in cpdm BMDC.\nWT and cpdm BMDC (2x106 cells in 0.5 mL complete medium) were stimulated with 100 ng/mL LPS (A) or 25 microg/mL poly I:C (B). At 0, 15, 30, and 60 minutes, whole-cell lysates were obtained and subject to immunoblots with antibodies against proteins involved in NF-kappaB, TBK1/IRF3, ERK1/2, and p38 signaling pathways. Beta-actin was used as loading control. (C) Cellular levels of p-IKK1/2 and p-IkappaBalpha in LPS- or poly I:C-stimulated BMDC were quantitated with ImageJ (NIH) and presented as trend lines. Results are representative of at least two independent experiments." ], "offsets": [ [ 0, 626 ] ] } ]

[ { "id": "PMC-3279418-24-Caption-Figure_6_T1", "type": "Protein", "text": [ "TBK1" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T2", "type": "Protein", "text": [ "IRF3" ], "offsets": [ [ 325, 329 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T3", "type": "Protein", "text": [ "ERK1" ], "offsets": [ [ 331, 335 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T4", "type": "Protein", "text": [ "2" ], "offsets": [ [ 336, 337 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T5", "type": "Protein", "text": [ "Beta-actin" ], "offsets": [ [ 367, 377 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T6", "type": "Protein", "text": [ "IKK1" ], "offsets": [ [ 432, 436 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T7", "type": "Protein", "text": [ "2" ], "offsets": [ [ 437, 438 ] ], "normalized": [] }, { "id": "PMC-3279418-24-Caption-Figure_6_T8", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 445, 457 ] ], "normalized": [] } ]

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[ { "id": "PMC-2626671-14-MATERIALS_AND_METHODS__text", "type": "abstract", "text": [ "ChIP and real-time PCR analysis.\n20 x 106 CD8+ T cells per immunoprecipitation were fixed by adding a 1/10th volume of fixation solution (11.1% formaldehyde, 100 mM NaCl, 1 mM EDTA, 0.5 mM EGTA, 50 mM Hepes) to 1 volume of culture media and were incubated for 10 or 30 min at RT. Fixation was stopped with 120 mM glycine on ice for 5 min. Fixed cells were washed 2x with cold PBS, 1x with cold solution I (10 mM Tris [pH 7.5], 10 mM EDTA, 0.5 mM EGTA, 1% Triton X-100), and 1x with cold solution II (10 mM Tris [pH 7.5], 1 mM EDTA, 0.5 mM EGTA, 200 mM NaCl). After washes, cell pellets were resuspended at 40 x 106 cells/ml in ChIP lysis buffer (150 mM NaCl, 25 mM Tris [pH 7.5], 1% Triton X-100, 0.1% SDS, 0.5% deoxycholate plus protease and phosphatase inhibitors), and chromatin was sheared with a sonicator to yield 0.5-1-kb DNA fragments. After preclearing the sheared chromatin with protein A-sepharose beads and removing 5% as input chromatin, immunoprecipitation was performed by adding optimized antibody amounts (per 20 x 106 cell equivalents: 2.5 mug anti-Eomes, 1:100 dilution anti-Runx3), followed by overnight incubation at 4degreesC; protein A-sepharose beads were added for the last 3 h of the incubation period. Beads were washed 2x with RIPA buffer (50 mM Tris [pH 8], 150 mM NaCl, 1 mM EDTA, 1% NP-40, 0.1% SDS, 0.5% deoxycholate), 1x with high salt buffer (50 mM Tris [pH 8], 500 mM NaCl, 1 mM EDTA, 1% NP-40, 0.1% SDS), and 1x with TE buffer. After the last wash, DNA was eluted by resuspending the beads in elution buffer (1% SDS, 100 mM NaHCO3). Both input and ChIP chromatin were then treated with RNase A (5 mug total) for 1 h at 37degreesC, followed by the addition of proteinase K (100 mug total) and overnight incubation at 65degreesC to reverse cross-linking. DNA was then purified with QIAquick columns (Gel Extraction Kit; QIAGEN) according to the manufacturer's instructions and resuspended in a 50-mul volume. For real-time PCR detection of immunoprecipitated targets using the SYBR Green PCR Kit, a standard curve was obtained with serial dilutions of input DNA for each sample, and 1 mul ChIP DNA was used per PCR reaction (performed in duplicates). Melt curves and agarose gels were analyzed to ensure amplification of specific target sequences. Refer to Table S1 (available at http://www.jem.org/cgi/content/full/jem.20081242/DC1) for a list of primer sets. The data are presented as the number of immunoprecipitated target sequences relative to input chromatin, assuming two copies of target sequence per cell equivalent used for the ChIP." ], "offsets": [ [ 0, 2577 ] ] } ]

[ { "id": "PMC-2626671-14-MATERIALS_AND_METHODS_T1", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 42, 45 ] ], "normalized": [] }, { "id": "PMC-2626671-14-MATERIALS_AND_METHODS_T2", "type": "Protein", "text": [ "Eomes" ], "offsets": [ [ 1067, 1072 ] ], "normalized": [] }, { "id": "PMC-2626671-14-MATERIALS_AND_METHODS_T3", "type": "Protein", "text": [ "Runx3" ], "offsets": [ [ 1094, 1099 ] ], "normalized": [] } ]

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[ { "id": "PMC-1310901-09-RESULTS__text", "type": "abstract", "text": [ "Absence of IRF-4 expression in leukemia cells is not due to promoter alterations\nWe have previously demonstrated a lack of IRF-4 expression in leukemia patients and specifically in CML T-cells (3). Here, we demonstrate the absence of IRF-4 expression in various hematopoietic cell lines, such as Jurkat, a T-cell leukemia, CML-T1, a bcr-abl-positive T-cell line, K-562, a bcr-abl-positve erythroleukemia, U-937, a monocytic leukemia, EM-2 and LAMA-84, bcr-abl-positve myeloid leukemia, but not in SD-1, a bcr-abl-positive acute lymphoblastic leukemia (pre B-ALL), RPMI-8226, a multiple myeloma and BV-173, a bcr-abl-positive B-cell line (Figures 1A and 5D). After sequencing of the IRF-4 promoter, it could be excluded that absence of IRF-4 expression in any of the above cell lines was due to genetic aberrations. However, 2 bp changes (nucleotide -1081, T to C and -1068, A to C) could be detected in both the IRF-4-positive BV-173 and the IRF-4-negative LAMA-84, EM-2 and K-562 (Figure 1B). At position -116 an A to C substitution was found in EM-2, K-562 and CML-T1, whereas Jurkat, BV-173 and SD-1 exhibited a mixed A/C sequence and U-937, LAMA-84 and RPMI-8226 no substitution at all (Figure 1B). Consequently, these alterations are unlikely to affect IRF-4 expression." ], "offsets": [ [ 0, 1275 ] ] } ]

[ { "id": "PMC-1310901-09-RESULTS_T1", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 11, 16 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T2", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T3", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 234, 239 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T4", "type": "Protein", "text": [ "bcr-abl" ], "offsets": [ [ 333, 340 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T5", "type": "Protein", "text": [ "bcr-abl" ], "offsets": [ [ 372, 379 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T6", "type": "Protein", "text": [ "bcr-abl" ], "offsets": [ [ 452, 459 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T7", "type": "Protein", "text": [ "bcr-abl" ], "offsets": [ [ 505, 512 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T8", "type": "Protein", "text": [ "bcr-abl" ], "offsets": [ [ 608, 615 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T9", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T10", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 735, 740 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T11", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 912, 917 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T12", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 942, 947 ] ], "normalized": [] }, { "id": "PMC-1310901-09-RESULTS_T13", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 1258, 1263 ] ], "normalized": [] } ]

[ { "id": "PMC-1310901-09-RESULTS_E1", "type": "Negative_regulation", "trigger": { "text": [ "Absence" ], "offsets": [ [ 0, 7 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_E2" } ] }, { "id": "PMC-1310901-09-RESULTS_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 17, 27 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T1" } ] }, { "id": "PMC-1310901-09-RESULTS_E3", "type": "Positive_regulation", "trigger": { "text": [ "due" ], "offsets": [ [ 53, 56 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_E1" } ] }, { "id": "PMC-1310901-09-RESULTS_E4", "type": "Negative_regulation", "trigger": { "text": [ "lack" ], "offsets": [ [ 115, 119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_E5" } ] }, { "id": "PMC-1310901-09-RESULTS_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 129, 139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T2" } ] }, { "id": "PMC-1310901-09-RESULTS_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 240, 250 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T3" } ] }, { "id": "PMC-1310901-09-RESULTS_E7", "type": "Gene_expression", "trigger": { "text": [ "positive" ], "offsets": [ [ 341, 349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T4" } ] }, { "id": "PMC-1310901-09-RESULTS_E8", "type": "Gene_expression", "trigger": { "text": [ "positve" ], "offsets": [ [ 380, 387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T5" } ] }, { "id": "PMC-1310901-09-RESULTS_E9", "type": "Gene_expression", "trigger": { "text": [ "positve" ], "offsets": [ [ 460, 467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T6" } ] }, { "id": "PMC-1310901-09-RESULTS_E10", "type": "Gene_expression", "trigger": { "text": [ "positive" ], "offsets": [ [ 513, 521 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T7" } ] }, { "id": "PMC-1310901-09-RESULTS_E11", "type": "Gene_expression", "trigger": { "text": [ "positive" ], "offsets": [ [ 616, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T8" } ] }, { "id": "PMC-1310901-09-RESULTS_E12", "type": "Negative_regulation", "trigger": { "text": [ "absence" ], "offsets": [ [ 724, 731 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_E13" } ] }, { "id": "PMC-1310901-09-RESULTS_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 741, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T10" } ] }, { "id": "PMC-1310901-09-RESULTS_E14", "type": "Gene_expression", "trigger": { "text": [ "positive" ], "offsets": [ [ 918, 926 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T11" } ] }, { "id": "PMC-1310901-09-RESULTS_E15", "type": "Gene_expression", "trigger": { "text": [ "negative" ], "offsets": [ [ 948, 956 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T12" } ] }, { "id": "PMC-1310901-09-RESULTS_E16", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1251, 1257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_E17" } ] }, { "id": "PMC-1310901-09-RESULTS_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1264, 1274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1310901-09-RESULTS_T13" } ] } ]

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[ { "id": "PMC-2065877-05-Results__text", "type": "abstract", "text": [ "Wild-Type and LMP1 Transgenic Lymphoma Cells Do Not Require IL4 and Stat6 Signaling\nTo investigate whether IL4 independence was due to endogenous IL4 expression, IL4 transcription was assessed by an Rnase protection assay (RPA). IL4 transcription was detectable with control RNA and faintly in the mouse lymphoma cell line K46mu (Figure 4A). However, IL4 transcription was not detectable in CD19+ MACS-purified B cells from wild-type lymphocytes (unpublished data), LMP1 transgenic lymphocytes, or lymphoma cells, although the GAPDH and L32 controls were effectively protected (Figure 4A). Activated Stat6 (pStat6), a target of the IL4 receptor pathway, was detected in the wild-type and LMP1 transgenic lymphocytes (Figure 4B). In contrast, pStat6 was barely detected in either the wild-type or LMP1 transgenic lymphoma cells. However, the pathway was not disabled, as treatment of the lymphoma cells with IL4 induced Stat6 phosphorylation (Figure 4C).\nAlthough wild-type lymphocytes cannot be maintained in culture with IL4 supplementation alone (Figure 3A), slight enhancement in MTS activity could be detected if the cells were analyzed at an earlier time point, at 1 d (Figure 4D) versus 3 d (Figure 3A) post-harvest. The enhancement of MTS activity induced by IL4 in wild-type lymphocytes could be neutralized by the addition of IL4 antibody (Figure 4D). However, neutralizing antibodies to IL4 did not affect the MTS activity of LMP1 transgenic lymphoma cells (Figure 4E). In summary, the wild-type and LMP1 transgenic lymphoma cells grew independently of IL4 treatment and did not require Stat6 signaling." ], "offsets": [ [ 0, 1613 ] ] } ]

[ { "id": "PMC-2065877-05-Results_T1", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 14, 18 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T2", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 60, 63 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T3", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 68, 73 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T4", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 107, 110 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T5", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 146, 149 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T6", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 162, 165 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T7", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 229, 232 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T8", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 351, 354 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T9", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T10", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 466, 470 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T11", "type": "Protein", "text": [ "GAPDH" ], "offsets": [ [ 527, 532 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T12", "type": "Protein", "text": [ "L32" ], "offsets": [ [ 537, 540 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T13", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T14", "type": "Protein", "text": [ "pStat6" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T15", "type": "Protein", "text": [ "IL4 receptor" ], "offsets": [ [ 632, 644 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T16", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 688, 692 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T17", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 796, 800 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T18", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 907, 910 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T19", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 919, 924 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T20", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1022, 1025 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T21", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1266, 1269 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T22", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1335, 1338 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T23", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1397, 1400 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T24", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1436, 1440 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T25", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1510, 1514 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T26", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1563, 1566 ] ], "normalized": [] }, { "id": "PMC-2065877-05-Results_T27", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1597, 1602 ] ], "normalized": [] } ]

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[]

[ { "id": "PMC-2664230-01-INTRODUCTION__text", "type": "abstract", "text": [ "The bacterial membrane component lipopolysaccharide (LPS) is capable of initiating phosphorylation and activation of multiple host intracellular protein kinases and transcription factors. Transcription factor activation, which results in the modulation of gene transcription and protein synthesis, is a critical element in the defense mechanism of the host immune system.1,2\nLPS-induced transcription factor activation has been shown to be a key regulator of tumor necrosis factor-alpha (TNF-alpha) production.3 TNF-alpha is a potent pro-inflammatory cytokine involved in a wide spectrum of cellular responses. Furthermore, TNF-alpha synthesis can be attenuated in immune cells exposed to phosphodiesterase (PDE) inhibition after challenge by a variety of pro-inflammatory stimulants.4 The signaling mechanisms affected by PDE inhibition, which ultimately lead to the downregulation of TNF-alpha production, have not been well characterized in inflammatory cells.\nClassically, it has been demonstrated that PDE inhibition results in the intracellular accumulation of the second messenger cyclic adenosine-3,5-monophosphate (cAMP) and subsequent activation of Protein kinase A (PKA).5 PKA activation then leads to the phosphorylation of the transcription factor cAMP-response element binding protein (CREB), transmission of signals into the nucleus, and the subsequent modulation of gene transcription.6 This apparently simple linear cascade does not fully explain the mechanism by which an elevation in the intracellular cAMP level exerts wide-ranging effects on multiple cellular functions. There is a growing body of evidence suggesting that cAMP may function through both PKA-dependent and -independent mechanisms.6-8\nLPS-induced activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has also been the focus of a great deal of research. It has been clearly demonstrated that agents that increase intracellular cAMP also inhibit NF-kappaB-dependent pro-inflammatory gene transcription, particularly of the TNF-alpha gene.9\nControversy exists regarding the exact mechanism(s) by which PDE inhibition down-regulates TNF-alpha production. Possibilities include, but are not limited to, inhibition of NF-kappaB DNA binding activity, downregulation of NF-kappaB transcriptional activity, increased CREB activation, and competition between NF-kappaB and CREB for common co-activators such as CREB binding protein (CBP). It is also not known whether these processes rely solely upon the activation of PKA.\nTherefore, the objective of the present study is to determine the effects of nonspecific PDE inhibition with 1-[5-oxohexyl]-3,7-dimethylxanthine (Pentoxifylline; PTX) on NF-kappaB and CREB activation in vitro in human mononuclear cells. With the use of specific inhibitors, we also investigated the role of PKA in LPS-induced TNF-alpha production." ], "offsets": [ [ 0, 2867 ] ] } ]

[ { "id": "PMC-2664230-01-INTRODUCTION_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 459, 486 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 488, 497 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 624, 633 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2027, 2036 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2135, 2144 ] ], "normalized": [] }, { "id": "PMC-2664230-01-INTRODUCTION_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2846, 2855 ] ], "normalized": [] } ]

[ { "id": "PMC-2664230-01-INTRODUCTION_E1", "type": "Regulation", "trigger": { "text": [ "regulator" ], "offsets": [ [ 446, 455 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E2" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 499, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_T1" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E3", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 634, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_T4" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E4", "type": "Negative_regulation", "trigger": { "text": [ "attenuated" ], "offsets": [ [ 651, 661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E3" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E5", "type": "Positive_regulation", "trigger": { "text": [ "lead" ], "offsets": [ [ 856, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E6" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E6", "type": "Negative_regulation", "trigger": { "text": [ "downregulation" ], "offsets": [ [ 868, 882 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E7" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E7", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 896, 906 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_T5" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1942, 1949 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E9" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E9", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1960, 1969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E10" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1992, 2005 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_T6" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E11", "type": "Negative_regulation", "trigger": { "text": [ "down-regulates" ], "offsets": [ [ 2120, 2134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E12" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 2145, 2155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_T7" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E13", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 2819, 2823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E14" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E14", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2838, 2845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_E15" } ] }, { "id": "PMC-2664230-01-INTRODUCTION_E15", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 2856, 2866 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-01-INTRODUCTION_T8" } ] } ]

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[]

[ { "id": "PMC-1447668-04-Results__text", "type": "abstract", "text": [ "Foxp3 Suppresses HIV-1 Gene Expression in Part through Blocking Activation of NF-kappaB\nIf Foxp3 functions as a repressor of NF-kappaB-dependent gene expression, then we hypothesized that Foxp3 overexpression could selectively down-regulate transcription from promoters previously shown to be responsive to NF-kappaB. To address this question, we examined the transcriptional activation of the HIV-1 LTR, which contains two tandem cis-acting NF-kappaB binding sites located between positions -102 and -81 with respect to the transcription initiation site [21]. NF-kappaB plays a crucial role in regulating gene expression directed from the HIV-1 LTR in CD4+ T cells [21]. Overexpression of full-length Foxp3, but not deltaFKH, in HEK 293T cells was able to inhibit basal activation of the HIV-1 LTR (Figure 3A), similar to what was previously demonstrated with the synthetic NF-kappaB reporter vector (Figure 2B). Furthermore, HIV-1 LTR activation was suppressed by full-length Foxp3 and deltaFKH in Jurkat T cells (Figure 3B). To demonstrate that Foxp3-mediated HIV-1 LTR repression was associated with interactions with NF-kappaB bound to the HIV-1 LTR, we compared basal activation of the HIV-1 LTR or an identical HIV-1 LTR lacking the NF-kappaB sites located between -102 and -81 (HIV-1 delta-kappaB LTR) (Figure 3C). This mutant HIV-1 LTR construct exhibited reduced levels of transcription compared to the parental HIV-1 LTR in purified healthy donor CD4+ T cells (unpublished data). However, directly comparing the effect of Foxp3 overexpression on the activation of these two viral promoters demonstrated that Foxp3 was more capable of suppressing transcriptional activation of the HIV-1 LTR (Figure 3D) compared to the mutated HIV-1 LTR (Figure 3E). These results suggest that Foxp3 down-regulation of HIV-1 LTR activation was mediated at least in part by cis-acting NF-kappaB binding sites. Residual levels of inhibition of the HIV-1 delta-kappaB LTR by Foxp3 may be due to NF-AT binding sites located upstream of the NF-kappaB sites within the HIV-1 LTR [22,23]." ], "offsets": [ [ 0, 2074 ] ] } ]

[ { "id": "PMC-1447668-04-Results_T1", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T2", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 91, 96 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T3", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 188, 193 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 653, 656 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T5", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 702, 707 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T6", "type": "Protein", "text": [ "deltaFKH" ], "offsets": [ [ 717, 725 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T7", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 978, 983 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T8", "type": "Protein", "text": [ "deltaFKH" ], "offsets": [ [ 988, 996 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T9", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 1048, 1053 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1458, 1461 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T11", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 1533, 1538 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T12", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 1619, 1624 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T13", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 1787, 1792 ] ], "normalized": [] }, { "id": "PMC-1447668-04-Results_T14", "type": "Protein", "text": [ "Foxp3" ], "offsets": [ [ 1965, 1970 ] ], "normalized": [] } ]

[ { "id": "PMC-1447668-04-Results_E1", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 194, 208 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1447668-04-Results_T3" } ] }, { "id": "PMC-1447668-04-Results_E2", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 672, 686 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1447668-04-Results_T5" } ] }, { "id": "PMC-1447668-04-Results_E3", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 672, 686 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1447668-04-Results_T6" } ] }, { "id": "PMC-1447668-04-Results_E4", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 1104, 1116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1447668-04-Results_T9" } ] }, { "id": "PMC-1447668-04-Results_E5", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1539, 1553 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-1447668-04-Results_T11" } ] } ]

[]

[]

[ { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION__text", "type": "abstract", "text": [ "Perforin and granzyme B expression are not appreciably regulated by T-bet\nTo test the model outlined in the previous paragraph directly, we compared the expression of IFN-gamma, perforin, and granzyme B in CD8+ T cells from WT and Tbx21 (T-bet)-deficient mice. As expected (17, 21), naive Tbx21-/- CD8+ T cells produced IFN-gamma poorly upon activation (Fig. 2 A). Notably, this deleterious effect of T-bet deficiency was only observed in differentiating CD8+ T cells until day 4 of culture but was almost completely mitigated by day 6 (Fig. 2 A). This most likely reflected compensation by Eomes, which was strongly induced between days 4 and 6 (Fig. 1). In contrast, T-bet-deficient T cells cultured for 6 d showed no defect in perforin mRNA expression (Fig. 2 B, compare lanes 1 and 4). We consistently observed a modest reduction in GzmB mRNA in T-bet-deficient T cells (Fig. 2 B, compare lanes 1 and 4), which did not translate into a decrease in expression of granzyme B protein (Fig. 2 C).\nTo examine the role of Eomes, we transduced naive CD8+ T cells from WT and Tbx21-/- mice with retroviruses containing internal ribosome entry site (IRES)-GFP that were either empty or encoded a strongly transactivating version of Eomes (Eo-VP16) (8), and expanded them for 6 d under our culture conditions. Eo-VP16, but not the empty GFP retrovirus, increased perforin expression in both WT and T-bet-deficient CD8+ T cells (Fig. 2 B, lanes 2, 3, 5, and 6). As expected, Eo-VP16 also rescued the early defect in IFN-gamma production observed in T-bet-deficient CD8+ T cells (Fig. 2 D). However, Eo-VP16 did not induce GzmB mRNA expression in either WT or T-bet-deficient cells; thus, the partial T-bet dependence of GzmB mRNA expression cannot be compensated for by Eo-VP16." ], "offsets": [ [ 0, 1771 ] ] } ]

[ { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T1", "type": "Protein", "text": [ "Perforin" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T2", "type": "Protein", "text": [ "granzyme B" ], "offsets": [ [ 13, 23 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T3", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 68, 73 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 167, 176 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T5", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 178, 186 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T6", "type": "Protein", "text": [ "granzyme B" ], "offsets": [ [ 192, 202 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T7", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 206, 209 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T8", "type": "Protein", "text": [ "Tbx21" ], "offsets": [ [ 231, 236 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T9", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 238, 243 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T10", "type": "Protein", "text": [ "Tbx21" ], "offsets": [ [ 289, 294 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T11", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 298, 301 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T12", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 320, 329 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T13", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 401, 406 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T14", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 455, 458 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T15", "type": "Protein", "text": [ "Eomes" ], "offsets": [ [ 591, 596 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T16", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 669, 674 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T17", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 730, 738 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T18", "type": "Protein", "text": [ "GzmB" ], "offsets": [ [ 837, 841 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T19", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 850, 855 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T20", "type": "Protein", "text": [ "granzyme B" ], "offsets": [ [ 966, 976 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T21", "type": "Protein", "text": [ "Eomes" ], "offsets": [ [ 1020, 1025 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T22", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 1047, 1050 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T23", "type": "Protein", "text": [ "Tbx21" ], "offsets": [ [ 1072, 1077 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T24", "type": "Protein", "text": [ "GFP" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T25", "type": "Protein", "text": [ "Eomes" ], "offsets": [ [ 1227, 1232 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T26", "type": "Protein", "text": [ "Eo-VP16" ], "offsets": [ [ 1234, 1241 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T27", "type": "Protein", "text": [ "Eo-VP16" ], "offsets": [ [ 1304, 1311 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T28", "type": "Protein", "text": [ "GFP" ], "offsets": [ [ 1331, 1334 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T29", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 1357, 1365 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T30", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 1392, 1397 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T31", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 1408, 1411 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T32", "type": "Protein", "text": [ "Eo-VP16" ], "offsets": [ [ 1468, 1475 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T33", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1509, 1518 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T34", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 1542, 1547 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T35", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 1558, 1561 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T36", "type": "Protein", "text": [ "Eo-VP16" ], "offsets": [ [ 1592, 1599 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T37", "type": "Protein", "text": [ "GzmB" ], "offsets": [ [ 1615, 1619 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T38", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 1652, 1657 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T39", "type": "Protein", "text": [ "T-bet" ], "offsets": [ [ 1693, 1698 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T40", "type": "Protein", "text": [ "GzmB" ], "offsets": [ [ 1713, 1717 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T41", "type": "Protein", "text": [ "Eo-VP16" ], "offsets": [ [ 1763, 1770 ] ], "normalized": [] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T42", "type": "Anaphora", "text": [ "which" ], "offsets": [ [ 598, 603 ] ], "normalized": [] } ]

[ { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 24, 34 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T1" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 24, 34 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T2" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 55, 64 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E1" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T3" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 55, 64 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E2" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T3" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 153, 163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T4" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 153, 163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T5" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 153, 163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T6" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E8", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 245, 254 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T8" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E9", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 311, 319 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T12" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E10", "type": "Negative_regulation", "trigger": { "text": [ "deficiency" ], "offsets": [ [ 407, 417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T13" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 617, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T15" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E12", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 675, 684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T16" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E13", "type": "Negative_regulation", "trigger": { "text": [ "defect" ], "offsets": [ [ 720, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E14" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E12" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E14", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 739, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T17" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E15", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 824, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T18" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E16" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E16", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 856, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T19" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E17", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 940, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E18" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 952, 962 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T20" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E19", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1347, 1356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E20" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T27" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1366, 1376 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T29" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E21", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 1398, 1407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T30" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E22", "type": "Negative_regulation", "trigger": { "text": [ "rescued" ], "offsets": [ [ 1481, 1488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E23" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T32" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E23", "type": "Negative_regulation", "trigger": { "text": [ "defect" ], "offsets": [ [ 1499, 1505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E24" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E25" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E24", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1519, 1529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T33" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E25", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 1548, 1557 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T34" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E26", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1608, 1614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E27" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T36" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E27", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1620, 1635 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T37" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E28", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 1658, 1667 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T38" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E29", "type": "Positive_regulation", "trigger": { "text": [ "dependence" ], "offsets": [ [ 1699, 1709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E30" }, { "role": "Cause", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T39" } ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_E30", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1718, 1733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T40" } ] } ]

[ { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_1", "entity_ids": [ "PMC-2626671-05-RESULTS_AND_DISCUSSION_T8", "PMC-2626671-05-RESULTS_AND_DISCUSSION_T9" ] }, { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_2", "entity_ids": [ "PMC-2626671-05-RESULTS_AND_DISCUSSION_T25", "PMC-2626671-05-RESULTS_AND_DISCUSSION_T26" ] } ]

[ { "id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_R1", "type": "Coreference", "arg1_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T42", "arg2_id": "PMC-2626671-05-RESULTS_AND_DISCUSSION_T15", "normalized": [] } ]

[ { "id": "PMC-3148254-08-Materials_and_Methods__text", "type": "abstract", "text": [ "Antibodies\nMouse anti-birch profilin antibody (4A6 [29]), rat anti-mouse CD40 (1C10 [30]) and a rat isotype control antibody (mAb72, Developmental Studies Hybridoma Bank, University of Iowa, Iowa City, IA) were isolated from hybridoma supernatants. FITC-labeled anti-mouse CD80 and an isotype control Ab were from eBiosciences. Rabbit anti-HOIP Ab [6] was the kind gift of Dr. Betty Eipper (University of Connecticut Health Center, Farmington, Connecticut). Goat anti-rat IgG, and HRP-labeled secondary Abs were from Jackson ImmunoResearch Laboratories, Inc. All other antibodies used were described previously [6]." ], "offsets": [ [ 0, 615 ] ] } ]

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[ { "id": "PMC-1310901-04-MATERIALS_AND_METHODS__text", "type": "abstract", "text": [ "Sequencing of the IRF-4 promoter\nFor analysis of the IRF-4 promoter region for permanent aberrations such as insertions/deletions or mutation, we PCR-amplified two fragments from genomic DNA, which was extracted from depicted cell lines with a commercial kit (Qiagen, Hilde, Germany) as recommended. The primers were 1-forward: 5'-TTGAGATGGAGTCTTGCTCTGT-3', 1-reverse: 5'-CCAGGACCTCAGGAGGCCAGTCA-3'; 2-forward: 5'-AGCGGTGAAACTGAGAGTGCGAGGT-3', 2-reverse: 5'-GCCACATCGCTGCAGTTTAG-3'. The products were cloned with the 'TOPO TA cloning kit' (Invitrogen, Groningen, The Netherlands). After bacterial amplification of the cloned PCR fragments by standard procedures, at least three clones from each sample were sequenced with an automated sequencer (ABI Prism 377, Applied Bio-systems, Foster City, USA) as recommended by the manufacturer." ], "offsets": [ [ 0, 835 ] ] } ]

[ { "id": "PMC-1310901-04-MATERIALS_AND_METHODS_T1", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "PMC-1310901-04-MATERIALS_AND_METHODS_T2", "type": "Protein", "text": [ "IRF-4" ], "offsets": [ [ 53, 58 ] ], "normalized": [] } ]

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[ { "id": "PMC-2065877-19-Caption-Figure_1__text", "type": "abstract", "text": [ "High LMP1 Expression Correlates with the Development of Lymphoma\nLMP1 expression is shown by (A) immunoblotting of purified B cells (CD19+) and (B) immunohistochemistry staining of spleen tissue from wild-type (WT) and LMP1 transgenic mice.\n(A) Lymphomas are identified with a number (1-7). Arrows indicate the LMP1-specific band and its degradation products as well as a non-specific band. Actin was used as a loading control.\n(B) White and red pulps are shown, but this architecture is lost upon development of lymphoma. Scale bar, 20 mum." ], "offsets": [ [ 0, 541 ] ] } ]

[ { "id": "PMC-2065877-19-Caption-Figure_1_T1", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 5, 9 ] ], "normalized": [] }, { "id": "PMC-2065877-19-Caption-Figure_1_T2", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 65, 69 ] ], "normalized": [] }, { "id": "PMC-2065877-19-Caption-Figure_1_T3", "type": "Protein", "text": [ "CD19" ], "offsets": [ [ 133, 137 ] ], "normalized": [] }, { "id": "PMC-2065877-19-Caption-Figure_1_T4", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 219, 223 ] ], "normalized": [] }, { "id": "PMC-2065877-19-Caption-Figure_1_T5", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 311, 315 ] ], "normalized": [] } ]

[ { "id": "PMC-2065877-19-Caption-Figure_1_E1", "type": "Positive_regulation", "trigger": { "text": [ "High" ], "offsets": [ [ 0, 4 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2065877-19-Caption-Figure_1_E2" } ] }, { "id": "PMC-2065877-19-Caption-Figure_1_E2", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 10, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2065877-19-Caption-Figure_1_T1" } ] }, { "id": "PMC-2065877-19-Caption-Figure_1_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 70, 80 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2065877-19-Caption-Figure_1_T2" } ] } ]

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[ { "id": "PMC-2889865-14-Materials_and_methods__text", "type": "abstract", "text": [ "RNA extraction\nJurkat T-cells were treated with NF-kappaB, JNK and PKC inhibitors for 2 h in 6-well plates followed by stimulation with 162 nM PMA for 24 h. At sampling the cells were pelleted followed by RNA extraction using 100 mul TRI-reagent (Sigma, USA). This was followed by addition of 100 mul chloroform/isoamylalcohol (24/1). The solutions were mixed by vortexing followed by centrifugation at 12,000 rpm for 15 min at 4degreesC. The upper phase was transferred to a new tube followed by addition of 100 mul iso-propanol and incubated at room temperature for 10 min. RNA was then pelleted by centrifugation at 12,000 rpm for 15 min at 4degreesC and washed with 70% ethanol. The RNA pellet was dissolved in 25 mul RNase free water and the yield and ratio (A260/A280) was determined using NanoVue (GE Healthcare, UK). The samples were stored at -80degreesC until further use." ], "offsets": [ [ 0, 882 ] ] } ]

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[ { "id": "PMC-3279418-10-Materials_and_Methods__text", "type": "abstract", "text": [ "Constructs and transfection\nThe complementary DNA (cDNA) of the mouse Sharpin gene was cloned and amplified from RAW264.7 RNA extracts. The primer sequences were forward, 5'-CC ATG GCG ATG TCG CCG CCC GCC GGC GGT; reverse, 5'- AAG CTT CTA GGT GGA AGC TGC AGC AAG A. The Sharpin cDNA was cloned into expression vector pFLAG-CMV-2. Murine fibroblasts and macrophages were were used to express recombinant SHARPIN protein. Cells (2x104) were seeded in 96-well treated plates the day before transfection. After overnight incubation, 200 ng pFLAG-SHARPIN plasmids were transfected with 0.5 ul Lipofectamine 2000. 24 hours later, cells were incubated with fresh culture medium. After another 24 hours, cells were lysed to confirm the FLAG-SHARPIN expression by immunoblots with anti-FLAG. Cells with no transfection and transfected with empty vector pFLAG-CMV-2 were used as negative control in all transfection experiments." ], "offsets": [ [ 0, 918 ] ] } ]

[ { "id": "PMC-3279418-10-Materials_and_Methods_T1", "type": "Protein", "text": [ "Sharpin" ], "offsets": [ [ 70, 77 ] ], "normalized": [] }, { "id": "PMC-3279418-10-Materials_and_Methods_T2", "type": "Protein", "text": [ "Sharpin" ], "offsets": [ [ 270, 277 ] ], "normalized": [] }, { "id": "PMC-3279418-10-Materials_and_Methods_T3", "type": "Protein", "text": [ "SHARPIN" ], "offsets": [ [ 403, 410 ] ], "normalized": [] }, { "id": "PMC-3279418-10-Materials_and_Methods_T4", "type": "Protein", "text": [ "SHARPIN" ], "offsets": [ [ 542, 549 ] ], "normalized": [] }, { "id": "PMC-3279418-10-Materials_and_Methods_T5", "type": "Protein", "text": [ "SHARPIN" ], "offsets": [ [ 733, 740 ] ], "normalized": [] } ]

[ { "id": "PMC-3279418-10-Materials_and_Methods_E1", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 383, 390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-10-Materials_and_Methods_T3" } ] }, { "id": "PMC-3279418-10-Materials_and_Methods_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 741, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-10-Materials_and_Methods_T5" } ] } ]

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[ { "id": "PMC-3279418-06-Results__text", "type": "abstract", "text": [ "Th2-biased immunogenicity of stimulated cpdm BMDC\nThe defective IL12 production (Fig. 3A) and Th2-dominant cytokine profile in cpdm mice [5] suggest that the absence of SHARPIN affects the ability of cpdm BMDC to induce T cell differentiation into effector cells. Co-culture of allogeneic naive CD4+ T cells with WT BMDC stimulated with LPS or poly I:C elicited robust IFNgamma production, whereas the concentration of IFNgamma in cpdm BMDC-T cell cultures was significantly lower after LPS stimulation (Fig. 7A), indicating impaired Th1-polarizing abilities of cpdm BMDC. In addition to TLR3/4 agonists, the TLR2 ligand Pam3CYS was used since it has been shown to induce both Th1 and Th2 responses [28]-[30]. Pam3CYS-matured WT BMDC induced robust IFNgamma production at a significantly higher level than cpdm BMDC (Fig. 7A). The reduced Th1 differentiation following Pam3CYS stimulation is consistent with the recent report of decreased IL12 production in cpdm macrophages following TLR2 stimulation [31]. In contrast, more Th2-specific IL4 cytokine was produced in the cpdm BMDC co-cultures than the WT control (Fig. 7B), suggesting Th2-skewed immunogenicity of cpdm BMDC. The production of Th17-specific cytokine IL17A following LPS stimulation of dendritic cells was similar between stimulated WT and cpdm BMDC cocultures (data not shown). Despite the distinct Th1- and Th2-stimulating abilities of WT and cpdm BMDC, they were equally effective in IL2 production from BMDC-T cell co-cultures except for poly I:C stimulation where WT BMDC induced more IL2 than cpdm BMDC (Fig. 7C). The Th2-biased stimulating capability of cpdm BMDC when co-cultured with allogeneic naive CD4+ T cells is consistent with the Th2-dominant cytokine phenotype observed in cpdm mice." ], "offsets": [ [ 0, 1766 ] ] } ]

[ { "id": "PMC-3279418-06-Results_T1", "type": "Protein", "text": [ "SHARPIN" ], "offsets": [ [ 169, 176 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T2", "type": "Protein", "text": [ "IFNgamma" ], "offsets": [ [ 369, 377 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T3", "type": "Protein", "text": [ "IFNgamma" ], "offsets": [ [ 419, 427 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T4", "type": "Protein", "text": [ "TLR3" ], "offsets": [ [ 588, 592 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T5", "type": "Protein", "text": [ "4" ], "offsets": [ [ 593, 594 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T6", "type": "Protein", "text": [ "TLR2" ], "offsets": [ [ 609, 613 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T7", "type": "Protein", "text": [ "Pam3CYS" ], "offsets": [ [ 621, 628 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T8", "type": "Protein", "text": [ "Pam3CYS" ], "offsets": [ [ 710, 717 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T9", "type": "Protein", "text": [ "IFNgamma" ], "offsets": [ [ 749, 757 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T10", "type": "Protein", "text": [ "Pam3CYS" ], "offsets": [ [ 869, 876 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T11", "type": "Protein", "text": [ "TLR2" ], "offsets": [ [ 985, 989 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T12", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1039, 1042 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T13", "type": "Protein", "text": [ "IL17A" ], "offsets": [ [ 1217, 1222 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T14", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 1453, 1456 ] ], "normalized": [] }, { "id": "PMC-3279418-06-Results_T15", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 1556, 1559 ] ], "normalized": [] } ]

[ { "id": "PMC-3279418-06-Results_E1", "type": "Negative_regulation", "trigger": { "text": [ "absence" ], "offsets": [ [ 158, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T1" } ] }, { "id": "PMC-3279418-06-Results_E2", "type": "Positive_regulation", "trigger": { "text": [ "elicited" ], "offsets": [ [ 353, 361 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_E3" } ] }, { "id": "PMC-3279418-06-Results_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 378, 388 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T2" } ] }, { "id": "PMC-3279418-06-Results_E4", "type": "Gene_expression", "trigger": { "text": [ "concentration" ], "offsets": [ [ 402, 415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T3" } ] }, { "id": "PMC-3279418-06-Results_E5", "type": "Positive_regulation", "trigger": { "text": [ "lower" ], "offsets": [ [ 475, 480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_E4" } ] }, { "id": "PMC-3279418-06-Results_E6", "type": "Positive_regulation", "trigger": { "text": [ "agonists" ], "offsets": [ [ 595, 603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T4" } ] }, { "id": "PMC-3279418-06-Results_E7", "type": "Positive_regulation", "trigger": { "text": [ "agonists" ], "offsets": [ [ 595, 603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T5" } ] }, { "id": "PMC-3279418-06-Results_E8", "type": "Binding", "trigger": { "text": [ "ligand" ], "offsets": [ [ 614, 620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T6" }, { "role": "Theme2", "ref_id": "PMC-3279418-06-Results_T7" } ] }, { "id": "PMC-3279418-06-Results_E9", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 734, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_E10" }, { "role": "Cause", "ref_id": "PMC-3279418-06-Results_T8" } ] }, { "id": "PMC-3279418-06-Results_E10", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 758, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T9" } ] }, { "id": "PMC-3279418-06-Results_E11", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 1056, 1064 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T12" } ] }, { "id": "PMC-3279418-06-Results_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1180, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T13" } ] }, { "id": "PMC-3279418-06-Results_E13", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 1223, 1232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_E12" } ] }, { "id": "PMC-3279418-06-Results_E14", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1457, 1467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T14" } ] }, { "id": "PMC-3279418-06-Results_E15", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1543, 1550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_T15" } ] }, { "id": "PMC-3279418-06-Results_E16", "type": "Positive_regulation", "trigger": { "text": [ "more" ], "offsets": [ [ 1551, 1555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3279418-06-Results_E15" } ] } ]

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[ { "id": "PMC-2791889-14-Experimental_Procedures__text", "type": "abstract", "text": [ "Real-Time Quantitative RT-PCR\nCells were harvested and restimulated in the presence of immobilized anti-CD3 (2 mug/ml) plus anti-CD28 (2 mug/ml) for 3 hr or immediately lysed. RNA was extracted and reverse-transcribed and cDNA was analyzed for the expression of cytokines and transcription factors by real-time PCR assay as before (Shoemaker et al., 2006). Target gene mRNA expression was quantified either with SYBR Green (Applied Biosystems) or with Master Mix (Applied Biosystems) and normalized to ubiquitin or HPRT mRNA levels, respectively." ], "offsets": [ [ 0, 546 ] ] } ]

[ { "id": "PMC-2791889-14-Experimental_Procedures_T1", "type": "Protein", "text": [ "CD3" ], "offsets": [ [ 104, 107 ] ], "normalized": [] }, { "id": "PMC-2791889-14-Experimental_Procedures_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 129, 133 ] ], "normalized": [] }, { "id": "PMC-2791889-14-Experimental_Procedures_T3", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 502, 511 ] ], "normalized": [] }, { "id": "PMC-2791889-14-Experimental_Procedures_T4", "type": "Protein", "text": [ "HPRT" ], "offsets": [ [ 515, 519 ] ], "normalized": [] } ]

[ { "id": "PMC-2791889-14-Experimental_Procedures_E1", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 520, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2791889-14-Experimental_Procedures_T3" } ] }, { "id": "PMC-2791889-14-Experimental_Procedures_E2", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 520, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2791889-14-Experimental_Procedures_T4" } ] } ]

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[ { "id": "PMC-2664230-10-RESULTS__text", "type": "abstract", "text": [ "PTX decreases LPS-induced NF-kappaB activation\nSince phosphorylation leads to ubiquitination and degradation of I-kappaBalpha and subsequent nuclear translocation of NF-kappaB, we first examined the effects of PTX on I-kappaBalpha. Cytoplasmic I-kappaBalpha phosphorylation was markedly increased following LPS stimulation when compared to control (100 +/- 0 vs. 20 +/- 18; P < 0.05). The addition of PTX significantly downregulated LPS-induced I-kappaBalpha phosphorylation (P = 0.02; Figure 2)\nIn a similar fashion, nuclear NF-kappaB p65 phosphorylation was increased following LPS stimulation (100 +/- 0 vs. 38 +/- 20; P < 0.01). PTX similarly decreased LPS-induced NF-kappaB p65 nuclear phosphorylation, a marker of NF-kappaB activation and nuclear translocation (100 +/- 0 vs. 40 +/- 6; P =0.03; Figure 3A).\nEMSAs were then performed to verify the PTX-induced alterations in nuclear phosphorylation resulted in similar effects on the DNA binding activity of NF-kappaB. The addition of PTX to LPS-stimulated mononuclear cells resulted in comparable downregulation of DNA binding activity, similar to the observed downregulation of NF-kappaB phosphorylation (Figure 3B)." ], "offsets": [ [ 0, 1173 ] ] } ]

[ { "id": "PMC-2664230-10-RESULTS_T1", "type": "Protein", "text": [ "I-kappaBalpha" ], "offsets": [ [ 112, 125 ] ], "normalized": [] }, { "id": "PMC-2664230-10-RESULTS_T2", "type": "Protein", "text": [ "I-kappaBalpha" ], "offsets": [ [ 217, 230 ] ], "normalized": [] }, { "id": "PMC-2664230-10-RESULTS_T3", "type": "Protein", "text": [ "I-kappaBalpha" ], "offsets": [ [ 244, 257 ] ], "normalized": [] }, { "id": "PMC-2664230-10-RESULTS_T4", "type": "Protein", "text": [ "I-kappaBalpha" ], "offsets": [ [ 445, 458 ] ], "normalized": [] }, { "id": "PMC-2664230-10-RESULTS_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 536, 539 ] ], "normalized": [] }, { "id": "PMC-2664230-10-RESULTS_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 679, 682 ] ], "normalized": [] } ]

[ { "id": "PMC-2664230-10-RESULTS_E1", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 69, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E2" } ] }, { "id": "PMC-2664230-10-RESULTS_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 97, 108 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_T1" } ] }, { "id": "PMC-2664230-10-RESULTS_E3", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 199, 206 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_T2" } ] }, { "id": "PMC-2664230-10-RESULTS_E4", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 258, 273 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_T3" } ] }, { "id": "PMC-2664230-10-RESULTS_E5", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 287, 296 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E4" } ] }, { "id": "PMC-2664230-10-RESULTS_E6", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 297, 306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E5" } ] }, { "id": "PMC-2664230-10-RESULTS_E7", "type": "Negative_regulation", "trigger": { "text": [ "downregulated" ], "offsets": [ [ 419, 432 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E8" } ] }, { "id": "PMC-2664230-10-RESULTS_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 437, 444 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E9" } ] }, { "id": "PMC-2664230-10-RESULTS_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 459, 474 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_T4" } ] }, { "id": "PMC-2664230-10-RESULTS_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 540, 555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_T5" } ] }, { "id": "PMC-2664230-10-RESULTS_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 560, 569 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E10" } ] }, { "id": "PMC-2664230-10-RESULTS_E12", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 570, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E11" } ] }, { "id": "PMC-2664230-10-RESULTS_E13", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 647, 656 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E14" } ] }, { "id": "PMC-2664230-10-RESULTS_E14", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 661, 668 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_E15" } ] }, { "id": "PMC-2664230-10-RESULTS_E15", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 691, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-2664230-10-RESULTS_T6" } ] } ]

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[ { "id": "PMC-3245220-06-Results__text", "type": "abstract", "text": [ "M-CSF-Dependent Activation of PKC Does Not Regulate the Classical NF-kappaB p65 Activation Pathway\nCanonical activation of NF-kappaB occurs via phosphorylation and degradation of IkappaBalpha leading to the release and nuclear translocation of the NF-kappaB p50/p65 heterodimer to transactivate target genes [37], [39]. Since conventional PKC activity was important in regulating M-CSF-induced NF-kappaB activation, we next investigated whether IkappaBalpha degradation was regulated by PKC. Cells were treated with cyclohexamide (CHX) to inhibit protein synthesis of IkappaBalpha, and its degradation was followed. As shown in Figure 5A, PKC inhibition with Ro-31-8220 did not alter M-CSF-induced IkappaBalpha degradation, suggesting that M-CSF-induced PKC activity augmented NF-kappaB transcriptional activity by an alternative pathway, like post-translational modification of NF-kappaB p65." ], "offsets": [ [ 0, 893 ] ] } ]

[ { "id": "PMC-3245220-06-Results_T1", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 76, 79 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T2", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 179, 191 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 258, 261 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 262, 265 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T5", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 445, 457 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T6", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 568, 580 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T7", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 698, 710 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 889, 892 ] ], "normalized": [] }, { "id": "PMC-3245220-06-Results_T9", "type": "Anaphora", "text": [ "an alternative pathway" ], "offsets": [ [ 815, 837 ] ], "normalized": [] } ]

[ { "id": "PMC-3245220-06-Results_E1", "type": "Regulation", "trigger": { "text": [ "Regulate" ], "offsets": [ [ 43, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_E2" } ] }, { "id": "PMC-3245220-06-Results_E2", "type": "Positive_regulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 80, 90 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T1" } ] }, { "id": "PMC-3245220-06-Results_E3", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 144, 159 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T2" } ] }, { "id": "PMC-3245220-06-Results_E4", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 164, 175 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T2" } ] }, { "id": "PMC-3245220-06-Results_E5", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 458, 469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T5" } ] }, { "id": "PMC-3245220-06-Results_E6", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 474, 483 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_E5" } ] }, { "id": "PMC-3245220-06-Results_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 539, 546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_E8" } ] }, { "id": "PMC-3245220-06-Results_E8", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 555, 564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T6" } ] }, { "id": "PMC-3245220-06-Results_E9", "type": "Regulation", "trigger": { "text": [ "alter" ], "offsets": [ [ 678, 683 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_E10" } ] }, { "id": "PMC-3245220-06-Results_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 690, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_E11" } ] }, { "id": "PMC-3245220-06-Results_E11", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 711, 722 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T7" } ] }, { "id": "PMC-3245220-06-Results_E12", "type": "Regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 767, 776 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_E13" } ] }, { "id": "PMC-3245220-06-Results_E13", "type": "Protein_modification", "trigger": { "text": [ "post-translational modification" ], "offsets": [ [ 844, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-06-Results_T8" } ] } ]

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[ { "id": "PMC-3245220-27-Caption-Figure_3__text", "type": "abstract", "text": [ "Inhibition of PKC or NF-kappaB induces apoptosis in MDMs.\n(A) MDMs were pre-incubated in RPMI medium containing inhibitors (Ro-31-8220: 5 microM, Go-6976: 5 microM, BAPTA/AM: 2.5 microM) for 30 minutes prior to the addition of M-CSF. As a control, untreated cells were incubated with dimethyl sulfoxide (DMSO). Cell lysates were resolved by SDS-PAGE and immunoblotted with antibody recognizing the active cleaved form of caspase-3. The blots were reblotted with beta-actin that served as a loading control. The ratio of active caspase-3 bands (17 kD and 19 kD) to beta-actin control was determined by densitometry analysis (bottom panel). Data represents the mean +/- S.E.M from two independent donors. (B) Apoptosis of the treated MDMs was also measured by Annexin V-FITC and propidium iodine (PI) staining and analyzed by flow cytometry. The percentage of surviving cells (Annexin V/PI negative) for the cells treated with vehicle/M-CSF was arbitrarily set as 100. Data shown represent the mean +/- S.E.M from three independent experiments. *The p-values of inhibitors/M-CSF compared to vehicle/M-CSF were <=0.05." ], "offsets": [ [ 0, 1115 ] ] } ]

[ { "id": "PMC-3245220-27-Caption-Figure_3_T1", "type": "Protein", "text": [ "beta-actin" ], "offsets": [ [ 462, 472 ] ], "normalized": [] }, { "id": "PMC-3245220-27-Caption-Figure_3_T2", "type": "Protein", "text": [ "caspase-3" ], "offsets": [ [ 527, 536 ] ], "normalized": [] }, { "id": "PMC-3245220-27-Caption-Figure_3_T3", "type": "Protein", "text": [ "beta-actin" ], "offsets": [ [ 564, 574 ] ], "normalized": [] }, { "id": "PMC-3245220-27-Caption-Figure_3_T4", "type": "Protein", "text": [ "Annexin V" ], "offsets": [ [ 758, 767 ] ], "normalized": [] }, { "id": "PMC-3245220-27-Caption-Figure_3_T5", "type": "Protein", "text": [ "Annexin V" ], "offsets": [ [ 875, 884 ] ], "normalized": [] } ]

[ { "id": "PMC-3245220-27-Caption-Figure_3_E1", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 520, 526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-27-Caption-Figure_3_T2" } ] }, { "id": "PMC-3245220-27-Caption-Figure_3_E2", "type": "Negative_regulation", "trigger": { "text": [ "negative" ], "offsets": [ [ 888, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMC-3245220-27-Caption-Figure_3_T5" } ] } ]

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