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1. OntoGene org pharmgkb Mozilla Firefox 206 Firefox Y v Filey View Mode Help Document PMID 2233715 UNSAVED CHANGES Annotation Show Pubmed Entry Concepts Interactions Loi On the mechanism for efficient repression of the interleukin 6 promoter by glucocorticoids enhancer 2 Reload Finish amp Save Help TATA box and RNA start site Inr motif occlusion F Conf Type 1 Name 1 Type 2 Name 2 2 Q N Abstract The feedback inhibition of interleukin 6_ IL 6 gene expression by lWG0GGrtiGGidS represents a regulatory m 0 99 Drug dexa Sort Ascending IL6 link between the endocrine and immune systems The mechanism of the efficient repression of the IL 6 promoter by V 1 00 Drug Z fi Sort Descending IL6 J dexamethasone Dex was investigated in HeLa cells transiently transfected with plasmid constructs containing different IL 6 promoter elements linked to the herpesvirus thymidine kinase gene tk promoter and the bacterial chloramphenicol Columns b 9 Type1 acetyltransferase gene cat and cotransfected with cDNA vectors constitutively expressing either the active wild type or inactive mutant human glucocorticoid receptor GR The induction by interleukin 1 tumor necrosis factor Concept phorbol ester or forskolin of IL 6 tk cat chimeric constructs containing a single copy of the IL 6 DNA segment vV Namel from 173 to 151 MRE I or from 158 to 145
2. was investigated in HeLa cells transiently PA449247 transfected With plasmid constructs containing different IL 6 promoter elements Term Properties Sa Ea Se ne tk promoter and the a PA449247 gene cat and cotransfected Type DRUG __ either the active wild type or inactive Comment mutant human glucocorticoid receptor GR_ The induction by_ interleukin 1 tumor necrosis factor phorbol ester or forskolin of IL 6 ae tk _cat chimeric constructs containing a single copy of the IL 6 DNA segment from 173 to 151 MRE I or from 158 to 145 MRE II which aaa eee derive from within the multiple cytokine and second messenger responsive enhancer MRE region was strongly repressed by Dex in a wild type GR Search Term Text dependent fashion irrespective of the inducer used The induction by _ Z pseudorabies virus ofan IL 6 construct containing the IL 6 TATA box and PharmGKB the RNA start site initiator or Inr element but not the MRE region was also oo repressed by Dex in the presence of wild type GR DNase footprinting showed that the purified DNA binding fragment of GR_ bound across the MRE UniProt the TATA box and the Inr site in the IL 6 promoter this footprint moderately related to the consensus GR responsive element GRE motif were present at the Inr the TATA box and the MRE II site in the IL 6 promoter although MRE I and a GR _ binding site between 201 and
3. Curcumin Simvastatin troglitazone Tetradecanoylphorbol Acetate Carbon Tetrachloride Nitric Oxide Dexamethasone Documentation as PDF Contact odin ontogene org For project information visit www ontogene org Logged in as fabio Annotation The user can then decide if the interaction is correct or not by clicking one of the options to the 2 Refresh Export Concepts Interactions x oe T T 2 right of the Interactions panel con Type1 Name1 Type2 Name2 O Gn E 1 00 disease Pulmonary Edema gene KIAAO101 H O 0 o If the interaction is believed to be F 100 dissase Pulmonary Edema gene TNFB A A 0 A correct the first box should be WI 100 dss se Pulmonary Edema gene TNF moe ticked see picture on the right 100 Gsease Pulmonary Edema gene ATMS H Hae 100 disease Pulmonary Edema gene PAF nme If it is believed to be wrong the 9 gene TNFB SS O 00m second box should be ticked Ss e mr PE Heed There are two other options In case the abstract does not provide sufficient information and the user is not able to make a decision without consulting the full text of the paper the third box should be ticked as in the picture below W 1 00 disease Pulmonary Edema gene TNE Finally if the document actually expresses that there is NO interaction between the two entities i e it is expressing a negative interaction the user should tick the last box which automatica
4. MRE II which derive from within the multiple cytokine and second J Type2 messenger responsive enhancer MRE region was strongly repressed by Dex ina wild type GR dependent fashion irrespective of the inducer used The induction by pseudorabies virus of an IL 6 construct containing the IL 6 TATA conois box and the RNA start site initiator or Inr element but not the MRE region was also repressed by Dex in the presence Name 2 A double click on the specific name or concept column opens a separate browser window where you can inspect the corresponding concept from the source database which depends on the specific ODIN customization it s CTD in the example below This functions works also in the Concepts panel in a similar way Notice that if you have a popup blocker this function will not work correctly Annotati f Concepts Interactions ficient repression of the interleukin 6 promoter by glucocorticoids enhancer TATA box Reload Export motif occlusion F Co Type 1 Concept 1 tion of interleukin 6 IL 6 gene expression by glucocorticoids represents a regulatory link between iW 3 30 chem MESH_D005576 ctamec The mechanicm of the efficiant ranreccinn nf the TI A nramoater huy deavamethacnne Dev m DN nham MECU MANATEE 0 0o Forskolin CTD ac ae re aale jlo WRESCEREBicocoricokts gene S I 8 Bonjoury ICEqueries Y ICE onlin j f ES 7 CLI DG Y G 7 CON
5. The induction by pseudorabies virus of an IL 6 construct containing the IL 6 TATA box and the RNA start site initiator or Inr element but not the MRE region was also repressed by Dex in the presence of wild type GR DNase I footprinting showed that the purified DNA binding fragment of GR bound across the MRE the TATA box and the Inr site in the IL 6 promoter this footprint overlapped that produced by proteins present in nuclear extracts from uninduced or induced HeLa cells Imperfect palindromic nucleotide sequence motifs moderately related to the consensus GR responsive element GRE motif were present at the Inr the TATA box and the MRE II site in the IL 6 promoter although MRE I anda GR binding site between 201 and 210 in IL 6 both lacked a discernible inverted repeat motif their sequences showed considerable similarity with negative GRE sequences in other Dex repressed genes Surprisingly chimeric genes containing MRE II which lacks a recognizable GACGTCA cyclic AMP and phorbol ester responsive motif were strongly induced by both phorbol ester and forskolin suggesting that MRE II ACATTGCACAATCT may be the prototype of a novel cyclic AMP and phorbol ester responsive element Taken together these observations suggest that ligand activated GR represses the IL 6 gene by occlusion not only ofthe inducible IL 6 MRE enhancer region but also of the basal IL 6 promoter elements Interleukin 1 Interleukin
6. and RNA start site Abstract The feedback inhibition of interleukin 6 IL 6 gene expression by glucocorticoids represents a regulatory link between the endocrine and immune systems The mechanism of the efficient repression of the IL 6 promoter by dexamethasone Dex was investigated in HeLa cells transiently transfected with plasmid constructs containing different IL 6 promoter elements linked to the p nt Lil E er a ID A ch ael lac aa tice Term Properties Type chem Value MESH_DO15850 Concepts Interactions Name Tumor Necro Interleukin 6 Tumor Necro Thymidine Tetradecano Pseudorabies Neoplasms Glucocorticoids Forskolin Dexamethas Chicrampheni Cyclic AMP phorbol CAT Annotation k mM oO 8 8 O O O O Freg amp Sort Ascending Type Sort Descending chem disease disease chem chem chem chem chem chem Refresh i E Concept S W MESH_D015850 a W 6208 a Mw 42549 a 399465 a E 411297 a E 2908 a E 2642 a E 2936 e a E 14781 Name Interleukin TBF INR TBP A IR B NR3C1 GCGR GSR GR Tas a Selected Q Unselected Export Score 16 11 11 11 BO BO Ro fo You can delete all selected or unselected concept occurrences in the document using the red buttons on top of the
7. 210 in IL 6 both lacked a discernible inverted repeat motif their sequences showed considerable similarity with negative GRE sequences in other Dex repressed genes Surprisingly chimeric genes containing MRE II which lacks a recognizable GACGTCA cyclic AMP and phorbol ester responsive motif were strongly induced by both phorbol ester and forskolin suggesting that MRE II ACATTGCACAATCT may be the prototype of a novel cyclic AMP and phorbol ester responsive element Taken together these observations suggest that ligand activated GR_ represses the IL 6 gene by occlusion not only of the inducible _ Ir e unn 2 s 2 2 a aT a o 2 lt Documentation as PDF Contact odin ontogene org For project information visit www ontogene org Logged in as It is also possible to visualize in a separate browser window the original PubMed entry from the PubMed webpage for the current article click on Show PubMed Entry on top of the Document panel Note that this functionality will not work correctly if your browser has a popup blocker OntoGene org pharmgkb Mozilla Firefox EJ Firefoxy v Filey View Moder Help 7 Document PMID 2233715 Annotation gt Show Pubmed Entry Concepts Interactions On the mechanism for efficient repression of the interleukin 6 promoter by glucocorticoids a Reload Finish amp Save Help enhancer TATA box and RNA start site
8. 7 che 14582 MOUSE 8 GEN 2 regulatory pathway in controlling the expression of the Gfi 1B gene but also provide the first 8 F Gite eee ieee Ge e evidence that Gfi 1B can exert its repression function by acting on GATA 1 mediated transcription a F GATA PETAR Peary o a without direct binding to the Gfi 1 site of the target genes Based on these data we propose that _ this negative auto regulatory feedback loop is important in restricting the expression level of Gfi 1B ie A myi a 3 thus optimizing its function in erythroid cells 1 E MEL 4218 HUMAN 17 GEN 2 12 El Gfi1B 14582 MOUSE GEN 2 INTRODUCTION Gfi 1B growth factor independence 1B is an erythroid specific Gfi family 13 P myb 4602 HUMAN 32 GEN 3 transcriptional factor which was identified by low stringency hybridization screening with a partial o i4 E BATA 1 821990_ARATH 1 GEN 4 Gfi 1 cDNA probe 1 Both Gfi 1 and Gfi 1B contain a SNAG domain that mediates transcriptional SE cee eo ee aah gt repression and a zinc finger domain at its C terminus for their DNA binding to the TAAATCAC t A T ES GCA recognition sequence 1 3 Expression of Gfi 1B is confined in erythroid lineage cells and 18 FE myb 4602_HUMAN 32 GEN 3 megakaryocytes in human 4 5 j whereas Gfi 1 is more abundant in the lymphopoietic thymus 6 wo E Gt 1B 14582_MOUSE 8 GEN 2 B 5o far p 1 cipi wafi j Socsi_ and Socs3 are known as the target genes of Gfi 1B 18 E G
9. File View Moder Inspectors Document PMID 2233715 UNSAVED CHANGES Show Pubmed Entry Concepts On the mechanism for efficient repression of the interleukin 6 promoter by glucocorticoids enhancer _ F Conf Ty TATA box and RNA start site Inr motif occlusion lt M F 1 00 Dn Abstract The feedback inhibition of interleukin 6 IL 6 gene E 0 77 Dn expression by glucocorticoids represents a regulatory link between the F o99 Dn endocrine and immune systems The mechanism of the efficient repression Alor oi i i ofthe IL 6 promoter by dexamethasone Dex was investigated in ile bes Tas O77 Di HeLa cells transiently transfected with plasmid constructs containing different IL 6 promoter elements linked to the herpesvirus thymidine kinase gene tk promoter and the bacterial chloramphenicol acetyltransferase gene cat yand cotransfected with cDNA vectors constitutively expressing either the active wild type or inactive mutant human glucocorticoid receptor GR The induction by _ phorbol ester or forskolin interleukin 1 tumor necrosis factor phorbol estei of IL 6 tk cat chimeric constructs containing a single copy of the _ de a n Term Properties MRE IL which verve cron wei tre mona pe cy toKIrte anu Securnu WT Then when you click again the term inspector opens and the span of words is highlighted in red File View Mode Ins
10. Inr motif occlusion F Conf Type 1 Name 1 Type 2 Name 2 ry 2 iN Abstract The feedback inhibition of interleukin 6 IL 6 gene expression by glucocorticoids represents a regulatory V 0 99 Drug dexamethasone Gene IL6 J link between the endocrine and immune systems The mechanism of the efficient repression of the IL 6 promoter by E 1 00 Drug glucocorticoids Gene IL6 dexamethasone Dex _ was investigated in HeLa cells transiently transfected with plasmid constructs containing different IL 6_ promoter elements linked to the herpesvirus On the mechanism for efficient repression of t Mol Cell Biol 1990 PubMed NCBI Mozilla Firefox o x chloramphenicol acetyltransferase gene cat and cotr active wild type or inactive mutant human glucocorticoid necrosis factor phorbol ester or forskolin of IL 6 tk IL 6 DNA segment from 173 to 151 MRE I or from 15 cytokine and second messenger responsive enhancer M dependent fashion irrespective of the inducer used The in containing the IL 6 TATA box and the RNA start site i repressed by Dex in the presence of wild type GR DN fragment of GR bound across the MRE the TATA box that produced by proteins present in nuclear extracts from u nucleotide sequence motifs moderately related to the consen FirefoxY On the mechanism for efficien 2 NCBI Resources v How To v PublMedgor Pubmed US National Library of Medicine as sind hod ER Li
11. a Lge Expression and function of interleukin 6 in y Visine a a ting dle regulatory link between the endocrine and immune systems The mechanism of the efficient epithelial J Cell 1991 effects Genes Suppressor drug effects Hela Cells drug e ePression of the IL 6 promoter by dexamethasone Dex was investigated in HeLa cells Positive and negative regulation of Interleukin 6 _ genetics Molecular Sequence Data Oligonu transiently transfected with plasmid constructs containing different IL 6 promoter elements collagenase gene expression Matrix Suppl 1992 drug effects genetics Receptors Glucocorticoid genetic linked to the herpesvirus thymidine kinase gene tk promoter and the bacterial See reviews _TATA Box drug effects Tetradecanoylphorbol Acetate p chloramphenicol acetyltransferase gene cat and cotransfected with cDNA vectors Necrosis Factor alpha_ pharmacology constitutively expressing either the active wild type or inactive mutant human glucocorticoid receptor GR The induction by interleukin 1 tumor necrosis factor phorbol ester or forskolin of IL 6 tk cat chimeric constructs containing a single copy of the IL 6 DNA segment from 173 See all Cited by 29 PubMed Central articles Documentation as PDF Contact odin ontogene org For project information visit www ontogene org Logged in as If you are unhappy about what you ha
12. by_ Search Databases eves bie sae oe m Tl E mmmh mek cnn bsimiee bho Tl E TATA hasr ana tha MARIA If you have made an erroneous selection click on Remove Term in the Inspector panel You can also remove terms by clicking them in the Document panel while pressing the SHIFT key In the Term Inspector you can manually edit the concept and the type of a term leave a comment or browse term databases click the down arrow next to Search Databases The specific set of DBs available depends on the version of ODIN but typically include Entrez Uniprot and a reference database for the specific application The following screenshots give a browsing example First an example from CTD Click on a term in the document panel pseudorabies in red in the example below Tick CTD in the Inspectors panel left then click Search Terms As this term is ambiguous we are given a Selection We choose Diseases 2 1e00 Pseudorabies CTD la lO 2 Q g ort y p Keyword Query Results CTD 0 2 marvin cl i Q ctdbase org basicQuery go bq pseudora 3 m Thay AR SPE e E ee a DOSNT e e a si E online CE Online FS hs Er O OG VINNI Uuta x e disease amp acc sans njour que HEH njour queries online SO njour v so 1 En Bonj ICE 60 M n Bonj ICEqueri ICE onli i HE j Keyword Query Results CTD iev View Mode a ae Your queries Contact us a 2 amp f
13. der Woude S E ECK120000198 b3387 100 00 T3 GENE S58 Department of Microbiology University of Pennsylvania Philadelphia Pennsylvania 19104 E E ECK120002276 b2092 100 00 60 GENE 59 Received 1 March 2002 Accepted 10 March 2002 aF ECK120000520 boas 100 00 oT GENE TU DESIRAT aE COND198 mutation 100 00 16 GC COLOMB 511 Phase variation of the outer membrane protein 4943 in E coli requires deoxyadenosine a A EFFECTO42 repression 100 00 15 EFFECT methylase Dam and OxyR E i i mes i S ECK120003891 yfgk 100 00 7 GENE 512 Previously it was shown that OxyR lis required for repression of the Ag43 encoding gene i agn43_ o and that Dam_ dependent methylation of three GATC target sequences in the E eee ape 1 regulatory region abrogates OxyR binding Eck120000950 b2S65 100 00 7 GENE 513 Here we report further characterization of _agn43_ transcription and its regulation COND231 plasmid 100 00 T GC COLOMB 514 Transcription was initiated from a sigma 70 dependent promoter at the G residue of the 4 E CONDOSO0 oxidative 100 00 6 ec eran GATI ence a CONDO47 nucleotides 100 00 6 Gc Document PMID 12029051 Annotation Show Pubmed Entry Concepts 56 Dam and OxyR j Dependent Phase Variation of agn43 Essential Elements and Evidence for a New Role of DNA Methylation 511 Phase variation of the outer membrane protein 4g43 in E coli requires deoxyadenosine methylase D
14. sentences containing the term that is being edited Notice that Repeated Term mode can be applied only to existing terms It cannot be applied to words which have not already been marked as terms if you do it the entire document seems to disappear In this case just unselect Repeated Term mode to go back to normal While the core of ODIN is similar in all versions it is a flexible tool and the version that is adapted to your task may look different We will look at two typical tasks in the following chapters working with interactions in section 6 and with organisms in section 7 6 Working with Interactions We are now going to look at the interactions that were suggested by the system Select one of the interactions the terms in the document which participate in this interaction will be highlighted and a colored frame will be placed around them to allow easy identification In the following screenshot the relation between Pulmonary edema and TNF alpha has been selected Note that a search has been performed in the reference database to confirm that the gene TNF actually corresponds to TNF alpha OntoGene org BioCreative 2013 CTD task Mozilla Firefox View History Bookmarks Tools Help uzh ch 13 ctd v B Google Q Lb A ge OntoGene org BioCreative 20 op File View Mode v Document PMID 8318674 UNSAVED CHANGES Annotation Show Pubmed Entry r Concep
15. that Gfi 1B induces a drastic expansion of erythroblast independent of its SNAG repression domain with a parallel Documentation as POF Contact odingontogene org For project information visit www ontogene org Refresh Selected Help Remove all protein genes concepts in tenms referring to the selected organism s Allows to quickly reduce all false i positives genes proteins iba arise f rom a wrong organism Help All organisms except for human disappear Also in the text fewer terms are highlighted If we click the Terms tab no change is immediately apparent we first need to press the Refresh button to see only human terms If we click on a term in the text the term inspector only gives human concept values which considerably reduces ambiguity 8 Saving your work In the File menu you can save your annotations Note that the save option might not be available in demo versions If you save a modified article a new file will be created and named in the format PMID CID xml Pubmed id and curator identifier If you reload the article using the same curator id the system will use this file if available This means your selections up to that point will be there when reloading an article that has been modified and saved before OntoGene org pharmgkb Mozilla Firefox mia lt ia Firefoxy View gt Mode Help Reload 2233715 UNSAVED CHANGES Annotation gt gt tres L G EE Entry
16. 6_ Oligonucleotide Probes RNA Neoplasm Receptors Glucocorticoid Tumor Necrosis Factor alpha Tetradecanoylphorbol Acetate Dexamethasone _ Forskolin Base Sequence Dexamethasone pharmacology Enhancer Elements Genetic drug effects Feedback Forskolin pharmacology Gene Expression drug effects Genes Suppressor drug effects Hela Cells drug effects immunology Humans Interleukin 1 pharmacology _ Interleukin 6 genetics Molecular Sequence Data Oligonucleotide Probes Promoter Regions Genetic RNA Neoplasm drug effects genetics Receptors Glucocorticoid genetics metabolism Restriction Mapping Second Messenger Systems TATA Box drug effects Tetradecanoylphorbol Acetate pharmacology Transcription Genetic Transfection Tumor Necrosis Factor alpha pharmacology http kitt cl uzh ch kitt bcms pharmgkbmeB Prolect information visit www ontogene org Logged in as 9 Summary of database search options Inside ODIN it is possible to launch searches into reference databases in several ways Here you can find a brief summary of the available options 1 From the Inspector panel when editing a term you can use the button Search Term Text 2 From the Concepts tab in the Annotation panel when clicking on the concept name or id a search in the reference DB which depends on the application can be launched 3 From the Interactions tab in the
17. ATA 1 821990 ARATH 1 GEN 4 mediated transcriptional repression 1 9 Since p21 is a cell cycle inhibitor and SOCS family 18 E DNA bind REMO_ARATH FROT 1 members are known to suppress cytokine signaling the functional role of Gfi 1B is considered to 20 F GATA 1 821990 ARATH 1 GEN 4 be important in controlling proliferation of erythrocyte megakaryocyte lineage cells Its importance 21 Gf 1B 14582 MOUSE 8 GEN 2 in erythropoiesis has been further highlighted by gene targeting experiment showing that Gfi 1B 22 F Gf 1B 14582 MOUSE 8 GEN 9 gene disruption aali in gminy lethality due to loss a red blood cell formation Sie l 23 F GATA 821990 ARATH1 GEN 4 Enforced expression experiment in early erythroid progenitor cells has shown that Gfi 1B induces a e 24 El RPMI 1231917 _RHIME GEN 1 E drastic expansion of erythroblast independent of its SNAG repression domain with a parallel Documentation as PDF Contact oding ontogens org For project information visit www ontogene org The article deals with human genes and proteins If we click the Organism tab of the Annotation panel we see that indeed the system assign the highest probability 51 3 to human We can discard all non human concepts e g interpretations terms as non human proteins as follows tick all organisms except human then click on the selected symbol as shown below Fie View Search Document PMC 1226314 Q Show P
18. Annotation panel You can mark all concepts of a certain type by selecting Mark by concept type from the View menu A search in the reference databases which depend on the application can be launched by double clicking on a concept name or identifier or by clicking on the plus symbol at the beginning of a line 4 Filtering options You can use filtering options which we describe now Applying filters only displays the sentences of interest to the annotator e Focus filter click on Focus in the Concepts tab Annotation panel to only display sentences that contain highlighted concepts according to your selection The following example shows a view of a document in which the three most frequent terms were selected for highlighting before and after clicking on Focus Document PMID 12029051 Show Pubmed Entry Concepts Refresh Q Selected Unselected 51 JOURNAL OF BACTERIOLOGY June 2002 p Focus lt Export a eee U i E Concept Name Score Freq Type 53 184 No 12 g E E ECK120011302 OxyR 100 00 131 TF 54 Copyright 2002 American Society for Microbiology E Gl BECK 1200090244 YR 100 00 131 TU 55 All Rights Reserved E wy 56 Dam and OxyR j Dependent Phase Variation of agng3 _ Essential Elements and Evidence SE lat ae Sa for a New Role of DNA Methylation fF ECK120003666 yzaX 100 00 75 GENE S7 Anu Wallecha Vincent Munster Jason Correnti Teresa Chan and Marjan van
19. Annotation panel clicking on the name of one of two entities participating in the interaction launches a search in the reference DB This function is not always available depending on the application 10 Known Bugs cdt version Terms in term tab in the annotation panel do not change to the new file if one file is closed with unsaved changes and a new file is opened ctd version If there are subordinate titles in the abstract such as Background or Methods all of these are converted to Abstract ctd version Tabs in the Annotation panel are not parallel anymore if they are added again ccg version File gt Reload does not work once some changes have been made Then it is also not possible to load a new file
20. Concepts Interactions Save hhanism for efficient repression of the interleukin G6 promoter by glucocorticoids 2 pana _ Finish amp Save E Helpi Show XML TATA box and RNA start site Inr motif occlusion F Cont Type1 mn Type 2 Name 2 7 B N Select Sample File e feedback inhibition of interlewkin 6 11 6 gene expression by glucocorticoids represents a regulatory V 0 99 Drug dexamethasone Gene IL6 F A F the endocrine and immune systems The mechanism of the efficient repression of the IL 6 promoter byf E 1 00 Drug glucocorticoids Gene IL6 DEX was investigated in HeLa cells transiently transfected with plasmid constructs containing Show Logged Actions 5 promoter elements linked to the herpesvirus thymidine kinase gene tk promoter and the bacterial chloramphenicol acetyltransferase gene cat and cotransfected with cDNA vectors constitutively expressing either the active wild type or inactive mutant human glucocorticoid receptor GR The induction by interleukin 1 tumor necrosis factor phorbol ester or forskolin of IL 6 tk cat chimeric constructs containing a single copy of the_ IL 6 DNA segment from 173 to 151 MRE I or from 158 to 145 MRE II which derive from within the multiple cytokine and second messenger responsive enhancer MRE region was strongly repressed by Dex in a wild type GR dependent fashion irrespective of the inducer used
21. K120009316 ECK120000950 COND231 CONDOS0 CONDO47 Name Score Freq OxyR 100 00 131 oxyR 100 00 131 mor 100 00 131 yzzX 100 00 75 b3387 100 00 T3 b2092 100 00 60 b da 100 00 27 mutation 100 00 16 repression 100 00 15 yigk 100 00 T spec 100 00 T b2965 100 00 T plasmid 100 00 T oxidative 100 00 6 nucleotides 100 00 6 Type TF TU GENE GENE GENE GENE GENE GC COLOMB EFFECT GENE TU GENE GC COLOMB 6c GC Note the visualization of selected concepts in the Document panel has now been changed from a frame to background highlight e Column Filters Document PMID 21908668 Annotation gt a show Pubmed Entry Concepts k 51 JOURNAL OF BACTERIOLOGY Now 2011 p Refresh Selected Unselected Focus lt j Export Help 52 5887 5897 Vol i Concept Name Score Freq Type a Zone 3193 No 21 0021 9193 11 12 00 doi 10 1128 7 JB Gi CONDNOUNDOZ mRNA 100 00 1 CON 2l Sort Ascari 056872 11 Copyright 2011 American Society for Microbiology i EY mmg S4 All Rights Reserved d FELIN repression 10000 2 EFFE Z Sort Descending S5 The Escherichia coli MntR Miniregulon Includes Genes Encoding 4 EFFECTOSO repressed 100 00 14 EFFE a Small Protein and an Efflux Pump Required for Manganese a EFFECTOS6 regulated FE EH Columns b Homeostasis Lauren S a E EFFECTON3 elevated z mS ap COND NOUN
22. NL DG 7 mOG 7 ACE gene gene a Your queries CONTACT us gene Illuminating how chemicals affect human health i gene Chemicals Name CAS RN ID Search Comparative Toxicogenomics Database m gene Home y O Forskolin Soramphenicol gene Gene Interactions Genes Diseases Comps pathways GO References eudorabies gene GR gene Name Forskolin phorbe gene CAS Type 1 Name 1H Naphtho 2 1 b pyran 1 one 5 acetyloxy 3 ethenyldodecahydro 6 10 10b trihydroxy OFA gene 3 4a 7 7 10a pentamethyl OFA citi Equivalent Term Coleonol FA gene CAS Registry Number 66428 89 5 DFA msa Definition Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP From the FA aie plant Coleus forskohlii Has antihypertensive positive ionotropic platelet aggregation inhibitory and smooth muscle relaxant activities also lowers intraocular pressure and promotes release of hormones from the pituitary gland menor Necrosis gene Structure 7 OFA gene p Thymidine gene kin 1alpha gene jeoplas ms gere FA gene TNF ALPHA gene Top oe CFTR Dexamethasone gene ance CYP19A1 orskolin gene 18 18 84i Ro 4 18 18 18 18 18 21 41 37 18 18 37t 18 18 18 22 RS 7 Constraining Organisms In the following example we show a version of ODIN that works with information on organisms Depending on your customization and field of application this may not be ava
23. ODIN OntoGene Document Inspector User Manual v 0 5 Fabio Rinaldi Simon Clematide Gerold Schneider Tilia Ellendorft http www ontogene org Introduction ODIN is a lightweight graphical interface for literature curation that can be run within a web browser Currently ODIN is coupled with the OntoGene pipeline which provides its text mining capabilities however nothing prevents ODIN from being interfaced with other text mining services as long as they support the same data exchange format In order to achieve optimal performance and user satisfaction the OntoGene team typically customizes the OntoGene pipeline and ODIN for the specific curation task OntoGene and ODIN have already been customized for some experiments in assisted curation in collaboration with well known databases in particular PharmGKB CTD and RegulonDB which have been described in a number of journal publications For details please see www ontogene org The purpose of this manual is to describe how ODIN can be used by a curator to perform some literature based curation tasks as for example exploring the entity annotations of a given article or validate interactions suggested by the system For any problem comment or suggestion please contact us at odin ontogene org Best regards The OntoGene Team http www ontogene org 1 Getting Started Enter your curator identifier in order to log in At least 2 characters are required Only alphanumeric ch
24. RIES CONTACT US 0 95 gene PAF gene TNFB Illuminating how chemicals affect human health E 0 95 gene PAF gene TNF 2 Genes Symbol name ID Search Comparative Toxicogenomics Database a 0 86 disease Pulmonary Edema gene LITAF C 0 86 disease Pulmonary Edema gene TNFA TNF 0 82 gene LITAF gene KIAA0101 A D D amp Basies Chemical Interactions Chemicals Diseases Gene Interactions Comps Pathways GO References 0 82 gene TNF ALPHA gene KIAA0101 D o o M 0 82 ne TNF ALPHA ne ATMS T Symbol TNF a gel ge 0 82 gene TNF ALPHA gene PAF Name tumor necrosis factor R ods g L 0 82 gene ATMS gene LITAF Synonyms APC1 protein ATP binding cassette sub family F GCN20 member 1 BOS_21587 Cachectin cTNF aw rm seh PEN Ania DADB 70P7 1 dif EGK_14705 GW7_04772 RATTNF SBAB 548A10 2 TNF a TNFA TNFalpha TNF ga 3 alpha TNF alpha TNF macrophage derived TNF monocyte derived Tnfsfla TNFSF2 tumor necrosis factor LJ 0 82 gene TNFA gene ATMS tumor necrosis factor alpha tumor necrosis factor alpha tumor necrosis factor alpha tumor necrosis factor 0 82 gene PAF gene LITAF mA mpm rn ligand superfamily member 2 tumor necrosis factor TNF superfamily member 2 tumour necrosis factor tumour F 0 82 gene PAF gene TNFA necrosis factor alpha xtnf xtnf alpha Top Interacting Lipopolysaccharides Chemicals resveratrol lipopolysaccharide Escherichia c
25. T Filters b 56 Waters Melissa Sandoval and Gisela Storz Cell Biology and a F EFFECTO repress Metabolism Program Eunice Kennedy Shriver National Institute of EFFECTOO re EFFECT Child Health and Human Development Bethesda Maryland l EFFECTOS regulate Received 26 July 2011 Accepted 28 August 2011 Manganese is a critical micronutrient for cells serving as an enzyme cofactor and a a a protecting against oxidative stress A EFFECTO26 induce S Yet manganese is toxic in excess and little is known about its Epi EFFECTO2T induced distribution in cells 4 EFFECTO30 induction 58 Bacteria control intracellular manganese levels by the E EFFECT010 decrease transcription regulator MntR z EFFECTOD decreed GC COLOMBOS 59 When this work began the only Escherichia coll K 12 gene D FAN Y 9 EFFECTOSS upregui ameebie known to respond to manganese via MntR_ repression was _mntH EFFECTO33 inhibition 100 00 2 EFFECT text The following filters can be chosen by clicking the down arrow which appears when hovering over the column labels of the Concepts tab in the Annotation panel e Type filters in the Type column you may restrict the view of concepts to only certain types of concepts which depend on the application This can be done by clicking the required boxes Limiting to specific types is a suitable preparatory step to using the Focus filter as described before in order to show sentence
26. Your gueries Contact us Iiluminating how chemicals affect human health ic tid luminating how chemicals affect human health gt pseudorabies Diseases gt Name ID Search e Inspectors i Comparative Toxicogenomics Database Comparative Toxicogenomics Database FIIs semen anivze Cowioed Hep gt em nsec I ae soaren Anazo Coin Save Cancel RemoveTerm Shd amp Keyword Query Pseudorabies Term R ye r N 5 items matched your keywords Basics Chemicals Comps pseudorabies 1 Caa Term Type Chemicals 1 1 Name Pseudorabies i Diseases 1 Synonyms Aujeszky Disease Aujeszky s Disease Aujeszkys Concept Values j Disease MESH_DO11557 Genes 2 Definition A highly contagious herpesvirus infection affecting GO Terms 5 the central nervous system of swine cattle dogs cats rats and other animals Comment Organisms 0 Categories Animal disease Nervous system disease Viral disease MeSH ID D011557 within the multiple cyto a and secc Search Databases region was strongly repressed by _Dex_ in a STEPS a ene ONO RST AASAD Search Term Text irrespective of the inducer used The induction By iim lesi virus o construct containing the IL 6 AABO and the RNA start site initiator or GRE M ctTo element but not the MRE region was also repressed by _Dex_ in the presence of wild m gt f type GR_ DNase I_ footpri
27. am Jand oxyr 512 Previously it was shown that oxyrR lis required for repression of the Ag43 encoding gene 2gn43 and that Dam dependent methylation of three GATC target sequences in the regulatory region abrogates oxyr binding 517 Since methylation also abrogates OxyR binding a this indicates that methylation plays a dual role in facilitating _agn43 transcription 518 In vitro transcription from an unmethylated template was repressed by oxyr i C1995 J which resembles the reduced form of OxyR S19 Consistent with this and the role of Dam in OxyR binding OxyR t C1995 protected from DNase I digestion the agn43_ regulatory region from 16 to 42 which includes the three GATC sequences 520 Deletion analyses of the regulatory region showed that a 101 nucleotide region of the agn43 regulatory region containing the promoter and this oxyr binding region was sufficient for Dam and oxyrR l dependent phase variation 533 Phase variation of agn43 is regulated at the transcriptional level and requires Dam and the oxidative stress response protein OxyR li 15 18 seict ian ie i Fanera M i C30 Tha nnmnnn aoenoulatare af An AT nhiann nu nerbhsink ie a PRIA hindina mentanin that Refresh Selected Unselected 2 Export Fi Focus HORHOROREBRARARARFOF8 SS 4 Concept ECK120011302 ECK120009244 ECK120000674 ECK120003666 ECK120000198 ECK120002276 ECK120000520 COND138 EFFECTO43 ECK120003891 EC
28. aracters and the symbols and are allowed It does not need to be an email address but make sure it is unique and use it consistently If you reload the page later on or open a new window logging in by entering a curator identifier is not necessary anymore as your curator id will be saved in your browser as a cookie If you want to change the curator id at any moment in the future this is possible by choosing Set Curator Identifier from the File menu File Viewr Moder Help Document Annotation amp Show Pubmed Entry Introduction This interface allows the reviewing and curation of term annotated XML documents Terms may be highlighted through the View Menu File Menu Reload reloads the current document Open Pubmed Abstract prompts the user to select a Pubmedcentral abstract number Save stores back in the server the current document as modified by the curator Show XML opens the formular containing the raw XML of the current document for copy and paste Select Sample File offers the user a pop up menu of a selection of Pubmedcentral file numbers Set Curator Email Address allows to modify the current email address which is used as an identifier for the curator Show Logged Actions displays a log of the user interactions for the current session View Menu The annotation tables which appear in the right hand side panel can be toggled Tick a term or all terms to highlight them Underlining of recog
29. d GR represses the IL 6 gene by occlusion not only of the inducible IL 6 MRE enhancer region but also of the basal IL 6 promoter elements Interleukin 1_ Interleukin 6_ Oligonucleotide Probes RNA Neoplasm _ Receptors Glucocorticoid Tumor Necrosis Factor alpha_ Tetradecanoylphorbol Acetate Dexamethasone Forskolin Base Sequence Dexamethasone pharmacology Enhancer Elements Genetic drug effects Feedback Forskolin pharmacology Gene Expression drug effects Genes Suppressor drug effects Hela Cells drug effects immunology Humans Interleukin 1 pharmacology Interleukin 6 genetics Molecular Sequence Data Oligonucleotide Probes Promoter Regions Genetic RNA Neoplasm _ drug effects genetics Receptors Glucocorticoid genetics metabolism Restriction Mapping Second Messenger Systems TATA Box drug effects Tetradecanoylphorbol Acetate pharmacology Transcription Genetic Transfection Tumor Necrosis Factor alpha_ pharmacology Documentation as PDF Contact odin ontogene org For project information visit www ontogene org Logged in as Help Annotation I Concepts Interactions 2 Reload Finish amp Save Help Conf Type Concept1 1 00 Drug PA452347 0 99 Drug PA449247 Name 1 Type Concept 2 glucocorticoi Gene PA198 dexamethas Gene PA198 Name 2 OQ QO 4N IL6 IL6 ODIN has actually 3 panels see figure below on the le
30. duced by both phorbol ester and forskolin suggesting that MRE II ACATTGCACAATCT may be the prototype of a novel cyclic AMP and phorbol ester responsive element Taken together these observations suggest that ligand activated GR represses the IL 6 gene by occlusion not only ofthe inducible IL 6 MRE enhancer region but also of the basal IL 6 promoter elements DNase I footprinting showed that the purified DNA binding fragment of GR bound across the MRE Interleukin 1 Interleukin 6 Oligonucleotide Probes RNA Neoplasm Receptors Glucocorticoid Tumor Necrosis Factor alpha Tetradecanoylphorbol Acetate Dexamethasone Forskolin Base Sequence Dexamethasone pharmacology Enhancer Elements Genetic drug effects Feedback Forskolin pharmacology Gene Expression drug effects Genes Suppressor drug effects Hela Cells drug effects immunology Humans Interleukin 1 pharmacology _ Interleukin 6_ genetics Molecular Sequence Data Oligonucleotide Probes Promoter Regions Genetic RNA Neoplasm drug effects genetics Receptors Glucocorticoid genetics metabolism Restriction Mapping Second Messenger Systems TATA Box drug effects Tetradecanoylphorbol Acetate pharmacology Transcription Genetic Transfection Tumor Necrosis Factor alpha pharmacology http kitt cl uzh ch kitt bcms pharmgkbmeB Prolect information visit www ontogene org Logged in as
31. ed Abstract Save the reviewing and curation of term annotated XML documents Terms may be Select Sample File p Show File 2233715 Show File 7903454 Set Curator Email Address ect a Pubmedcentral abstract number ment as modified by the curator aw XML of the current document for copy and Show File 9430134 paste Show File 9529129 Select Sample File nu of a selection of Pubmedcentral file numbers Set Curator Email 4 Show File 9731005 current email address which is used as an identifier for the cun Show File 10459572 Show Logged Actioi interactions for the current session View Menu Show File 10748001 The annotation table hand side panel can be toggled Tick a term or all terms to highlight th Show File 10773015 terms is always enabled If a table a Supported term types are curre Show Organisms Tah aas ihs Soh aan ability in the current document are shown The annotator can e g di Show File 20168265 ise from a wrong organism Show Term Table Sh ces of each term as they appear in the document and the concept s tt Show File 20172323 le row to show the document occurrence Show Concept Table mcepts their organism and their frequency and salience score if ava Show File 20305671 Shows the mapping of a concept to the term in the text and the term nj disease yellow Show File 20410877 Show Interaction Ti the text with confidence score and the types of concepts of the two S
32. ft the Inspector panel in the center the Document panel and on the right the Annotations panel The Inspector panel is closed at the beginning and opens automatically if you click on a term or if you click the double arrow on its top at the left of the interface In the same way you can also open and close the Annotation panel on the right We will discuss the Inspector panel in section 5 overlapped that produced by proteins present in nuclear extracts from uninduced or induced HeLa cells Imperfect palindromic nucleotide sequence motifs OntoGene org pharmgkb Mozilla Firefox so Ez Firefoxy v File View Moder Help Inspectors Document PMID 2233715 saaa a Term Inspector Show Pubmed Entry Concepts Interactions Save Cancel Remove Temm Show On the mechanism for efficient repression of the interleukin 6 Reload _ _Finish amp Save Help Term promoter by glucocorticoids enhancer TATA box and RNA Conf Type1 Name 1 Type 2 Name 2 Q 0O BN start site Inr motif occlusion mrmr m wer dexamethasone W 0 99 Drug dexamethasone Gene IL6 a E Term Type Abstract The feedback inhibition of interleukin 6 IL 6 gene expression E 1 00 Drug glucocorticoids Gene IL6 by glucocorticoids represents a regulatory link between the endocrine and DRUG immune systems The mechanism of the efficient repression of the IL 6 promoter Concept Values by Sekar Dex
33. how File 20416945 Each annotation Mode Menu In term mode single terms are displayed and curated in the term inspector panel on mouse click New terms are created by mouse clicks on adjacent words In repeated term mode every term of the same ontological class can be mass edited Further items on the Help Menu explain how to browse and how to annotate documents _ Annotation gt gt Documentation as PDF Contact odin ontogene org For project information visit www ontogene org Logged in as The Open Pubmed Abstract option allows you to enter any pubmed identifier The OntoGene system will fetch the corresponding abstract from PubMed and process it before delivering the results to the ODIN interface The process could last a couple of seconds depending on the length of the abstract 2 The ODIN panels Below you can see an example of an annotated document the PubMed abstract is in the Document panel left in the picture and the interactions appear in the Annotation panel right side of the picture If the Annotation panel is empty you can select an annotation type in the View menu The available annotations depend on the version of ODIN and the customized application Typically they are application specific concepts such as genes proteins diseases organisms and interactions among them In the example we see interaction annotation The concepts annotation has also been selected in the View me
34. ilable We open the sample PubMed file 1226314 and select organism and term tables from the View menu if your version of ODIN offers them Your screen may now look as follows OntoGene org Biocreative I IAT Fie View Search Mode Help Document PMC 1226314 Annotation gt a Show PubmedCentral show Pubmed Entry Organisms Terms GATA i mediates auto regulation of Gfi 1B transcription in K562 cells Fatah En spats Bint Tem Concepts Typ 7 A Abstract Gfi 1B growth factor independence 1B gene is an erythroid specific transcription factor whose expression plays an essential role in erythropoiesis Our laboratory has previously 1 E Gata See es A a defined the human Gfi 1B promoter region and shown that GATA 1 mediates erythroid specific Gfi 2 E GiB 14582 MOUSE 8 GEN 2 1B transcription By further investigating the regulation of the Gfi 1B promoter here we report 3 E GATA 1232960_RHIME GEN 2 that i Gfi_ 1B transcription is negatively regulated by its own gene product ii GATA 1 4 E Gi 1B 1458 MOUSE 8 GEN 2 instead of Gfi 1B binds directly to the Gfi 1 like sites in the Gfi 1B promoter and iii Gfi 1B 5 E GATA 1 821990 ARATH 1 GEN 4 suppresses GATA 1 mediated stimulation of Gfi 1B promoter through their protein interaction 6 P GATA 1 821990 ARATH 1 GEN 4 These results not only demonstrate that interaction of GATA 1 and Gfi 1B participates in a feedback
35. it twice e AND Filters in the view menu you can select filters which are applied in combination increasingly restricting the number of sentences that are displayed When you select a type only sentences containing that type are displayed If several types are selected only sentences which contain all selected types are displayed For example you are able to inspect only those sentences which contain both genes and effects View Mode Show Term Table Annotation E Show Concept Table e only Escherichia coli K 12 gene Refresh Selected Q Unselected Focus 2 Export Highlight by concept type p Ese via MntR_ repression was _mntH gt concept Nama Pon Freg Typa a a AND filters p al Contains GENE EFFECTO4S repression 100 00 26 EFFECT text e rybA jis al Contains EFFECT a a E EFFECTO repressed 100 00 14 EFFECT text Reset View ean abam seo _ Contains COND NOUN S E EFFECTOS6 regulated 100 00 16 EFFECT text 511 Overproduction of Mnt _ Contains GC tivity while gt EFFECTO13 elevated 100 00 6 EFFECT text a lack of MntS_ perturbs pri Contains RNA nt E E EFFECT 41 repress 100 00 A EFFECT text repression of ot E Contan TF F EFFECToo2 actwate 100 00 1 EFFECT text S12 We also provide evident in T ebN ae i P me M ada i a 7 a F EFFECTOS regulate 100 00 6 EFFECT text which encodes a putative eff iair e gulated by ee mR ne a F EFFECTOS2 up
36. kine and second messenger responsive enhancer MRE region was strongly repressed by Dex in a wild type GR_ dependent fashion irrespective of the inducer used The induction by pseudorabies virus ofan IL 6 construct containing the IL 6 TATA box and the RNA start site initiator or Inr element but not the MRE region was also repressed by Dex in the presence of wild type GR _ DNase I footprinting showed that the purified DNA binding fragment of GR bound across the MRE the TATA box and the Inr site in the IL 6 promoter this footprint overlapped that produced by proteins present in nuclear extracts from uninduced or induced HeLa cells Imperfect palindromic nucleotide sequence motifs moderately related to the consensus GR_ responsive element GRE motif were present at the Inr the TATA box and the MRE II site in the IL 6 promoter although MRE I and a GR _ binding site between 201 and 210 in IL 6 both lacked a discernible inverted repeat motif their sequences showed considerable similarity with negative GRE sequences in other Dex repressed genes Surprisingly chimeric genes containing MRE II which lacks a recognizable GACGTCA cyclic AMP and phorbol ester responsive motif were strongly induced by both phorbol ester and forskolin suggesting that MRE II ACATTGCACAATCT may be the prototype of a novel cyclic AMP and phorbol ester responsive element Taken together these observations suggest that ligand activate
37. lly select also the first one TNE Hoe v 1 00 disease Pulmonary Edema gene You can optionally resize the columns of the interaction table and remove some of them If you hover over the column titles a down arrow between the columns will appear use it in order to open a menu The menu contains options for sorting and a submenu called Columns which can be used to select which columns to show For example the columns Concept1 and Concept2 could be removed because the same information can be obtained by hovering the mouse over the columns Name1 and Name2 An additional submenu called Filters might appear in some columns Its function has been explained in section 4 of wild type GR the TATA box and the Inr site in the IL 6 promoter this footprint overlapped that produced by proteins present in nuclear extracts from uninduced or induced HeLa cells Imperfect palindromic nucleotide sequence motifs moderately related to the consensus GR responsive element GRE motif were present at the Inr the TATA box and the MRE II site in the IL 6 promoter although MRE I anda GR binding site between 201 and 210 in IL 6 both lacked a discernible inverted repeat motif their sequences showed considerable similarity with negative GRE sequences in other Dex repressed genes Surprisingly chimeric genes containing MRE II which lacks a recognizable GACGTCA cyclic AMP and phorbol ester responsive motif were strongly in
38. mits Advanced Help Display Settings v Abstract Send to V FREE FREE im article A MCB eee in PubMed _ p A Mol Cell Biol 1990 Nov 10 11 5736 46 C eeeeeeeeeeeeeeeeecieeieiaiseeiliceeemensieemsiaeeseens On the mechanism for efficient repression of the interleukin 6 Related citations Inr the TATA box and the MRE II site in the IL 6 pro and 210 in IL 6 both lacked a discernible inverted repeatm promoter by glucocorticoids enhancer TATA box and RNA start A multiple cytokine and second messenger negative GRE sequences in other Dex _ repressed genes site Inr motif occlusion responsive element in the enha Mol Cell Biol 1989 recognizable GACGTCA cyclic AMP and phorbol ester res and forskolin suggesting that MRE II ACATTGCACAAT ester responsive element Taken together these observatio by occlusion not only of the inducible IL 6 MRE enhance Interleukin 1 Interleukin 6 Oligonucleotide Probes Factor alpha_ Tetradecanoylphorbol Acetate Dexamethaso Repressor to activator switch by mutations in the Ray A LaForge KS Sehgal PB first Zn finger of th Proc Natl Acad Sci U S A 1991 Rockefeller University New York New York 10021 6399 i i Repression of the human glycoprotein hormone Abstract alpha subunit gene by glucoc Mol Endocrinol 1991 The feedback inhibition of interleukin 6 IL 6 gene expression by glucocorticoids represents
39. nized terms is always enabled If a table a Supported term types are currently Show Organisms Table Organisms and thair nrohahility in the current document are shown The annotator can e g delete all false p Curator E Mail x nism Show Term Table Shows the indivi r y appear in the document and the concept s to which they li Please enter your e mail address iment occurrence Show Concept Table Gene Protein LOO Y m and their frequency and salience score if available are dis concept to the term in the text and the term type gene blue Show Interaction Table Shows the OK Cancel ace score and the types of concepts of the two participating e Each annotation table has its own help button Mode Menu In term mode single terms are displayed and curated in the term inspector panel on mouse click New terms are created by mouse clicks on adjacent words In repeated term mode every term of the same ontological class can be mass edited Further items on the Help Menu explain how to browse and how to annotate documents Documentation as PDF Contact odin ontogene org For project information visit www ontogene org Logged in as xtzx Once you are logged into the system select a file to inspect You can either use Open Pubmed Abstract from the File menu or you can also select one of the provided sample files from Select Sample File as shown below File View gt Mode Help Open Pubm
40. nting showed that the purified DNA binding fragment of Ey 1445 me hag rae _GR_ bound across the MRE the M7ANBGR and the MA site in the IL 6 promoter a 7 2046 a er this footprint overlapped that produced _by proteins present in nuclear extracts from E H zs 1 Notice that this function will not work if your browser has a popup blocker as it is the default in Chrome In order to use it deactivate the popup blocker Second an example from PharmGKB on dexamethasone bal Ls KE pharmgkb or org search search action exactMatch false amp query dexz 7 7 C L S7 Google R PharmGKB HOME PUBLICATIONS FEEDBACK SIGN IN IL Pharmacogenomics Knowledge Implementation Home Search i Download Help Consortia Search for dexamethasone a Database Search Limit results to _ Genes Variants _ Drugs _ Diseases Pathways _ Publications Results 1 20 of 401 sorted by relevance C Dosing Guidelines _ Drug Labels _ Clinical Annotations _ Genetic Tests Drug dexamethasone pgx research Aliemate names Adexone Meroseb D Aeroseb Dex Anaflogistica Aphtasolon Aphthasolone Auxiron Azium Bisu Ds Galonal Corson Gorsone Cortisumman DEX DAM Decacor Decacortin Decaderm Decadron Decadron Tablets Elixir Gene RASD1 Name RAS dexamethasone induced 1 Alternate symbols AGS1 DEXRAS1 MGC 26290 Drug thiabendazole Altemate names Apl Luster Arbotect Bioguard Bovi
41. nu and can be brought to the foreground by clicking on the Concepts tab in the Annotation panel A brief online introduction to each annotation table is also available in the Help menu within the Annotation panel top right corner The Help menu is currently being revised File View Mode Document PMID 2233715 Show Pubmed Entry On the mechanism for efficient repression of the interleukin 6 promoter by glucocorticoids enhancer TATA box and RNA start site Inr motif occlusion Abstract The feedback inhibition of interleukin 6 IL 6 gene expression by glucocorticoids represents a regulatory link between the endocrine and immune systems The mechanism of the efficient repression of the IL 6 promoter by _ dexamethasone Dex was investigated in HeLa cells transiently transfected with plasmid constructs containing different _ IL 6 promoter elements linked to the herpesvirus thymidine kinase gene tk promoter and the bacterial chloramphenicol acetyltransferase gene cat and cotransfected with cDNA vectors constitutively expressing either the active wild type or inactive mutant human glucocorticoid receptor GR The induction by interleukin 1 tumor necrosis factor phorbol ester or forskolin of IL 6 tk cat chimeric constructs containing a single copy of the IL 6 DNA segment from 173 to 151 MRE I or from 158 to 145 MRE II which derive from within the multiple cyto
42. pectors Document PMID 2233715 UNSAVED CHANGES Term Inspector Show Pubmed Entry Save Cancel Remove Term Show On the mechanism for efficient repression of the interleukin 6 promoter Term by glucocorticoids enhancer TATA box and RNA start site Inr motif occlusion phorbol ester Abstract The feedback inhibition of interleukin 6 IL 6 gene expression by glucocorticoids represents a regulatory link between the endocrine and immune systems Term Type The mechanism of the efficient repression of the IL 6 promoter by dexamethasone E Concept Values Dex_ was investigated in HeLa cells transiently transfected with plasmid constructs containing different IL 6 promoter elements linked to the herpesvirus thymidine kinase gene k promoter and the bacterial chloramphenicol acetyltransferase gene cat and cotransfected with cDNA vectors constitutively expressing either the active wild type or inactive mutant human glucocorticoid receptor ER The induction by interleukin 1 Comment tumor necrosis factor or forskolin of JL 6 tk cat chimeric constructs containing a single copy of the IL 6 DNA segment from 173 to 151 MRE I or from 158 to 145 MRE II which derive from within the multiple cytokine and second messenger responsive enhancer MRE region was strongly repressed by _Dex_ in a wild type GR dependent fashion irrespective of the inducer used The induction
43. regul 100 00 6 EFFECT text Remove filter my ind 513 Deletion of _mntP_ lead ensitivity and EFFECTO28 MOM d EFPEGI l to elevated intracellular manganese levels 5 F EFFECTO27 induced 100 00 7 EFFECT text S44 Upon binding to manganese MntR_ binds promoter DNA to 4H T EFFECTOSO induction 10000 5 EFFECT text repress or activate transcription of its target genes 15 30 a E EFFECTO10 decrease 100 00 1 EFFECT text 545 In enterobacteria the only genes known to be regulated by z F FFFECTOOS decreased 100 00 2 EFFECT text MntR when this work began were mntH and 5888 WATERS ET AL T a a E EFFECTOSS upregul 100 00 2 EFFECT text 4 EFFECTOS3 inhibition 100 00 2 EFFECT text 548 In some Gram positive bacteria the MntR analog seems to A E EFFECTO42 represses 100 00 1 EFFECT text Note that unchecking the boxes does not work correctly Instead you need to select Remove filter to get back to the original situation 5 The Term Inspector You can manually add terms which were not correctly annotated as follows Double click on a word to be able to annotate it in the inspector The first click selects the word a red dotted frame appears the second click opens the term inspector the word is highlighted in red and the Inspectors panel becomes visible on the left side If you want to create a multi term word single click on one of the words then its neigbour etc until the term has the appropriate span
44. s containing terms of the selected types e Name filters in the Name column the view of concepts can be restricted to certain names In order to do so click on the Filter option and enter a name e g Serotonin in the text field Only one name can be chosen at a time e Frequency filters in the Filter option of the Frequency column an exact frequency or range of frequency can be chosen to only display terms which occur the given number of times Values can be entered in three possible ways either by entering a number after the gt sign to only display terms with a frequency greater than the given number by entering a number after the lt sign to only display terms with a frequency lower than the given number or by entering a number after the sign to display only terms with the exact given frequency Score filters in the Filter option of the Score column terms can be restricted according to their confidence score assigned by the system The confidence score expresses the confidence of the system in respect to correctness of the displayed terms High scores correspond to a high probability that a term is correct and in most cases it makes sense to sort out terms with a lower probability The boxes for entering the filter values for the Score Filters work in the same way as the boxes of the Frequency Filters described above In order to remove all of the above filters press the Refresh button it might be necessary to do
45. ts Interactions Pulmonary edema land shock after high dose aracytine C for lymphoma possible role of MNEalpha and PAF pamen ee uan Abstract Four out of 23 consecutive patients treated with high dose Ara C for lymphomas in our institution developed a strikingly similar syndrome during the perfusion It ema Type 2 Damea pma hamog 0 0 a was characterized by the onset of fever diarrhea shock acute renal failure metabolic acidosis weight gain and leukocytosis Thorough 1 00 disease Pulmonary Edema gene KIAA0101 J bacteriological screening failed to provide evidence of infection Sequential biological assays of IL 1 IL 2 TNF and PAF were performed during Ara C infusion to F 1 00 disease Pulmonary Edema gene TNFB DA A oe ten patients including the four who developed the syndrome ONF and PAF activity was found in the serum of respectively two and four ofthe cases but not in the six J 1 00 disease Pulmonary Edema gene TNF A A F controls As INF and PAF are thought to be involved in the development of septic shock and adult respiratory distress syndrome we hypothesize that high dose Ara C 1 00 disease Pulmonary Edema gene ATMS may be associated with cytokine release 1 00 disease Pulmonary Edema gene PAF j 0 95 gene TNFB gene KIAA0101 IF 0 95 gene TNF gene KIAA0101 TNF CTD Mozilla Firefox co ml wal iw 0 95 gene ATMS gene TNFB ctdbase org deta ype gene amp a ag E 095 gene ATMS gene TNF Hea YOUR QUE
46. ubmedCentral Show Pubmed Entry GATA i mediates auto regulation of Gfi 1B transcription in K562 cells Abstract Gfi 1B growth factor independence 1B gene is an erythroid specific transcription factor whose expression plays an essential role in erythropoiesis Qur laboratory has previously defined the human Gfi 1B promoter region and shown that GATA 1 mediates erythroid specific Gfi 0 0578636294286605 E 1B transcription By further investigating the regulation of the Gfi 1B promoter here we report FIN r a that i Gfi 1B transcription is negatively regulated by its own gene product ii GATA 1 DROME N 0 0336846853420541 instead of Gfi 1B binds directly to the Gfi 1 like sites in the Gfi 1B promoter and iii Gfi 1B IF BPP4 0 026533820671173 suppresses GATA 1 mediated stimulation of Gfi 1B promoter through their protein interaction wl CERAE 0 02653382067 1173 These results not only demonstrate that interaction of GATA 1 and Gfi 1B participates in a feedback ical ARATH 0 0 0253729660168092 regulatory pathway in controlling the expression of the Gfi 1B gene but also provide the first wl NEUCR 0 0199003655033797 evidence that Gfi 1B can exert its repression function by acting on GATA 1 mediated transcription gon SET yioo AON neroni ENO sunt TETEE a T F PIG 0 0199003655033797 without direct binding to the Gfi 1 site of the target genes Based on these data we propose that enna ee this negative auto reg
47. ulatory feedback loop is important in restricting the expression level of Gfi 1B wy ae ae 0 0176648911118334 eee thus optimizing its function in erythroid cells E BPT4 ee enn 0 01 32669103355865 na E STRPU 0 01 32669103355865 INTRODUCTION Gfi 1B growth factor independence 1B is an erythroid specific Gfi family transcriptional factor which was identified by low stringency hybridization screening with a partial Gfi 1_ cDNA probe 1 Both Gfi 1_ and Gfi 1B contain a SNAG domain that mediates transcriptional repression and a zinc finger domain at its C terminus for their DNA binding to the TAAATCAC A T GCA recognition sequence 1 3 Expression of Gfi 1B is confined in erythroid lineage cells and megakaryocytes in human 4 5 whereas Gfi 1 is more abundant in the lymphopoietic thymus 6 8 So far p21 cip1 wafl_ Socs1_ and Socs3 are known as the target genes of Gfi 1B mediated transcriptional repression 1 9 Since p21 is a cell cycle inhibitor and SOCS family members are known to suppress cytokine signaling the functional role of Gfi 1B is considered to be important in controlling proliferation of erythrocyte megakaryocyte lin age cells Its importance in erythropoiesis has been further highlighted by gene targeting experiment showing that Gfi 1B gene disruption results in embryonic lethality due to loss of red blood cell formation 10 Enforced expression experiment in early erythroid progenitor cells has shown
48. ve done so far on an article you can reload it using the Reload option from the File menu Beware all your actions so far on that article will be lost We will show how to save your work in section 7 3 Working with Concepts Click on the Concepts tab in the Annetation Annotation panel All concepts are displayed Clicking on the right of the column title you can sort them by the column of your choice If you drag the column fringe the column gets broader or smaller If you double click on a concept or name a definition is provided in a Separate window ODIN tries to provide this definition from a reference database Which database is used for reference depends on the specific application for which ODIN has been customized Ticking the box on the left highlights all occurrences of the corresponding concept in the text Document PMID 2233715 Concepts Interactions Refresh Selected Unselected 2f Export ma ea e e S HEE Hoo E E 0 0000o o a Concept MESH_D048069 MESH_D015850 MESH_D014409 MESH_D013936 MESH_DO13755 MESH_D011557 MESH_D009369 MESH_D005938 MESH_DO005576 MESH_D003907 MESH_D002701 MESH_D000242 MESH_C033085 BT a show Pubmed Entry On the mechanism for efficient repression of the interleukin 6 promoter by glucocorticoids enhancer motif occlusion
49. zole Chemviron TK 100 Cropasal Drawipas Eprofil Equivet TZ Equizole Hokustar hp Hymush Lombristap Mertec Mertect Mertect 160 Mertect 3401 Mertect isp Metasol TK 10 Drug ciprofloxacin Within the PharmGKB database with two additional clicks you might get to the screen shown below depending on what you are looking for po dexamethasone PharmGKB PharmGKB HOME PUBLICATIONS FEEDBACK SIGN IN Knowledge Implementation oH 1 dexamethasone PharmGKB PG KE pharmgkb org drug PA449247 previousQuery dexamethasone 5 j ha g Home Search Download Help Consortia ig Druc SMALL MOLECULE from search dexamethasone dexamethasor j dexamethasone Ii Clinical PGx PGx Research Overview Brand Mixture Names DEX M Ade Ak Trol Suspension DXM h Dexamethasone Neomycin Desametasone Sulfate Polymyxin B Sulfate Desametasone Dcit flogisti Ciprodex Ciprofloxacin Desamethasone i Ciprofloxacin Hydrochloride Dexametasona LINN aai PAdd9247 Repeated Term Mode The Term Inspector has two modes of operation which can be selected in the Mode menu Single Term and Repeated Term In Single Term mode only the single instance which you select is changed In Repeated Term mode all occurrences inside the document are changed In order to assist the annotator in his or her decision whether all occurrences are of the same type ODIN only displays the
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