| bmp5 | |||||||||||||||||||||||||||||
| Type | Gene1 | Effect | Gene2 | Sentence | Perturbation methods | Time of Interaction in evidence | territories of interaction or Tissue | Evidence for Direct | Authors | Journal | PubYear | Volume | Pages | MedLine Reference | Connectivity | # of References | Found In Pathways | Journal Link | Journal Reference | Mechanism | URN | ISSN | Issue | LocatorString | MedlineTA | PubMonth | p-value [Evol. Bioinformatics 2007:3(197)] | TextPath | Title |
| Regulation | bmp7 | positive | acvr1 | OP-1 alone increased ActR-I, BMPR-IA, and BMPR-II mRNA levels, but did not change the BMPR-IB level. | Endocrinology | 16985:48:00 | 2 | 4 | Zebrafish_Bmp2b_20080727 | http://endo.endojournals.org/cgi/content/full/138/10/4181 | v138 i10 p4181 | urn:agi-Regulation:inout-urn:agi-llid:655:out-urn:agi-llid:90::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11165484&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477300005414 | ||||||||||||||||
| Expression | bmp7 | negative | acvr1b | Prdm1 expression is reduced in snh (BMP7) mutant embryos. | overexpression | 5.25 | blastoderm | 2 | Thierry Lepage | Development | 2006 | 133 | 2189 | ||||||||||||||||
| Regulation | bmp7 | positive | admp | Noggin (Smith and Harland, 1992), Chordin (Sasai et al., 1994), dominant-negative BMP receptor type I (tBR) (Graff et al., 1994 and Suzuki et al., 1994) and dominant-negative BMP7 (CmBMP7) (Hawley et al., 1995) are able to induce admp (Fig. 1B) as well as | 2 | 1 | Zebrafish_Chordin_20080727 | urn:agi-Regulation:inout-urn:agi-llid:655:out-urn:agi-llid:165679::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=10640703&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0925477399002452 | ||||||||||||||||||||
| Expression | bmp7 | positive | admp | When ventral BMP2/4/7 signals are depleted, admp expression increases, allowing for self-regulation. | egg | 41577:04:00 | 2 | 4 | Zebrafish_Bmp2b_20080727 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:165679::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11784095&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012160601904944 | ||||||||||||||||||
| Expression | bmp7 | positive | alk8 | Ved expression is up-regulated during gastrulation in snh/bmp7 signaling mutants. | mutant embryos | 9 | mesoderm | 1 | Mary C. Mullins | Development | 2001 | 128 | 859 | ||||||||||||||||
| Expression | bmp7 | positive | bmp4 | bmp4 does not regulate the expression of itself or other BMPs bmp4 can activate its own expression in Xenopus overexpression experiments (Jones et al., 1992), and in zebrafish, both BMP2b and BMP7 are required for the maintenance of bmp2b, bmp7, and bmp4 | 2 | 4 | Zebrafish_Bmp2b_20080727 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:652::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=17727832&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)01214-6 | ||||||||||||||||||||
| Expression | bmp7 | negative | bmp4 | OP-1 downregulated the BMP-4, -5, and -6 mRNA levels by a maximal of 2-fold, 1.5-fold, and 6-fold, respectively. | bone | Cell | 63546:07:00 | 2 | 12 | Zebrafish_Bmp2b_20080727 | http://www.cell.com/cgi/content/full/91/1/127.1 | v91 i1 p127.1 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:652::negative | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=12682283&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12682283 | |||||||||||||||
| Binding | bmp7 | neutral | chd | Chordin also binds BMP2, bmp4, and BMP7 in a way similar to noggin ( 20 ). | J. Biol. Chem | 54447:20:00 | 2 | 5 | Zebrafish_Chordin_20080727 | http://www.jbc.org/cgi/content/full/278/26/24113 | v278 i26 p24113 | urn:agi-Binding:inout-urn:agi-llid:8646:inout-urn:agi-llid:655: | digtext:http://www.springerlink.com/content/jha0upj83ar9ja0h/fulltext.html | ||||||||||||||||
| Expression | bmp7 | positive | cpb1 | Similarly, bone morphogenetic proteins (particularly bmp4 and BMP7) are produced in the lateral mesodermand have been implicated in the induction of pancreas-specific gene expression, at least inexplanted endoderm (Kumar et al., 2003). | 2 | 2 | Zebrafish GRN from literatures-7-24-2008 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:1360::positive | digtext:C:\Documents and Settings\yuh\Desktop\zebrafish GRN Literatures\Sagerstrom-CG-2007.pdf | url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cDesktop%5czebrafish%20GRN%20Literatures%5cSagerstrom-CG-2007.pdf):pdf | |||||||||||||||||||
| Binding | bmp7 | neutral | fgf8a | However, in the chick fgf8a is only expressed in a ventral, posterior domain within each pouch, which abuts the domain of Bmp7 and is not in contact with the placode (Graham and Begbie, 2000), suggesting that fgf8a and Bmp7 interact to define territories | 2 | 2 | Zebrafish_Bmp2b_20080727 | urn:agi-Binding:inout-urn:agi-llid:655:inout-urn:agi-llid:2253: | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=16077092&db=pubmed&url=http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=16077092 | ||||||||||||||||||||
| Binding | bmp7 | neutral | fsta | We provide data which show that Follistatin binds BMP-7 and BMP-2 at low affinities and that the binding is reversible. | muscle | Genes & Dev | 50001:05:00 | 2 | 17 | Zebrafish_Bmp2b_20080727 | http://www.genesdev.org/cgi/content/full/12/10/1438 | v12 i10 p1438 | urn:agi-Binding:inout-urn:agi-llid:655:inout-urn:agi-llid:10468: | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=9882485&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(98)99003-0 | |||||||||||||||
| Binding | bmp7 | neutral | gdf7 | Our findings suggest that a GDF7:BMP7 heterodimer functions as a roof plate-derived repellent that establishes the initial ventral trajectory of commissural axons. | J. Biol. Chem | 28003:05:00 | 2 | 7 | Zebrafish GRN from literatures-7-24-2008 | http://www.jbc.org/cgi/content/full/280/37/32122 | v280 i37 p32122 | urn:agi-Binding:inout-urn:agi-llid:655:inout-urn:agi-llid:151449: | digtext:C:\Documents and Settings\yuh\Desktop\zebrafish GRN Literatures\Hammerschmidt-M-2007.pdf | url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cDesktop%5czebrafish%20GRN%20Literatures%5cHammerschmidt-M-2007.pdf):pdf | |||||||||||||||
| Expression | bmp7 | neutral | myf5 | However, a 3-day incubation with BMP-7 increased Myf5 expression in wild-type cells, whereas MyoD appaeared to be unaffected. | Cell Sci | 13098:43:00 | 2 | 3 | Zebrafish_myod_20080731 | http://jcs.biologists.org/cgi/content/full/117/8/1457 | v117 i8 p1457 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:4617::unknown | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=9450925&db=pubmed&url=http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=9450925 | ||||||||||||||||
| Expression | bmp7 | neutral | myod1 | CDMP-1 enhanced the suppression of the OP-1-induced expression of the myogeneic differentiation regulator MyoD. | Genes & Dev | 54131:06:00 | 2 | 3 | Zebrafish_myod_20080731 | http://www.genesdev.org/cgi/content/full/12/3/290 | v12 i3 p290 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:4654::unknown | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=9450925&db=pubmed&url=http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=9450925 | ||||||||||||||||
| Expression | bmp7 | negative | ndr1 | Ved expression is down-regulated at late blastula stage in snh/bmp7 mutants. | overexpression | 8 | margin | 2 | Hammerschmidt, M. | Curr Biol | 2007 | 17 | 475 | ||||||||||||||||
| Binding | bmp7 | neutral | nog1 | Toward that end, we have determined the crystal structure of the antagonist Noggin bound to BMP-7. | bone | Genes & Dev | 15018:04:00 | 2 | 16 | Zebrafish_Chordin_20080727 | http://www.genesdev.org/cgi/content/full/12/10/1438 | v12 i10 p1438 | urn:agi-Binding:inout-urn:agi-llid:9241:inout-urn:agi-llid:655: | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=17483092&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=17483092 | |||||||||||||||
| Binding | bmp7 | neutral | nog1 | Pro35 of Noggin makes a similar knob-into-hole interaction with BMP-7 as Ile2 of CV-2 VWC1 with BMP-2. | 2 | 1 | Zebrafish_Chordin_20080727 | urn:agi-Binding:inout-urn:agi-llid:80757:inout-urn:agi-llid:655: | digtext:http://www.sciencedirect.com/science?_ob=GatewayURL&_origin=inwardhub&_urlversion=4&_method=citationSearch&_piikey=S1534580708001172&_referrer=www.ncbi.nlm.nih.gov/pubmed/18477456?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPa... | ||||||||||||||||||||
| Expression | bmp7 | positive | phox2b | BMP signaling is required locally inendoderm for epibranchial neurogenesis BMP7 has been shown to induce Phox2b expression in chick explants of pharyngeal ectoderm (Begbie et al., 1999) but it is not known: (1) whether BMP signaling is required for this p | 2 | 5 | Zebrafish GRN from literatures-7-24-2008 | urn:agi-Expression:inout-urn:agi-llid:655:out-urn:agi-llid:8929::positive | digtext:C:\Documents and Settings\yuh\My Documents\MedScan Reader Projects\zebrafish development\Tzu-Min's old papers\Thomas F. Schilling 2005.pdf | url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cMy%20Documents%5cMedScan%20Reader%20Projects%5czebrafish%20development%5cTzu-Min%27s%20old%20papers%5cThomas%20F.%20Schilling%202005.pdf):pdf | |||||||||||||||||||
| Expression | bmp7 | positive | prdm1a | Ved expression is up-regulated during gastrulation in snh/bmp7 signaling mutants. | mutant embryos | 11.66 | neural plate border | 1 | Kristin Bruk Artinger | Developmental Biology | 2005 | 278 | 347 | ||||||||||||||||
| Expression | bmp7 | positive | ved | overexpression of BMPs compromises endoderm formation, formation of endoderm precursors is negatively regulated by BMPs on the ventral side. | mutant embryos | 4 | superficial blastomere | 1 | Cotelli, F. | Dev Dyn | 2004 | 230 | 494 | ||||||||||||||||
| Binding | activin | neutral | bmp7 | BMP-7 can interact with activin type I and type II receptors in addition to BMP-2/BMP-4 receptors ( 26 , 28 ). | J. Biol. Chem | 27935:23:00 | 2 | 5 | Zebrafish_Chordin_20080727 | http://www.jbc.org/cgi/content/full/272/35/22046 | v272 i35 p22046 | urn:agi-Binding:inout-urn:agi-llid:655:inout-urn:agi-go:0016915: | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=17483092&db=pubmed&url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=17483092 | ||||||||||||||||
| Expression | acvr1 | positive | bmp7 | injected mRNA encoding a constitutively active version of Alk8 can rescue the strong dorsalization of bmp7/snailhouse mutants | overexpression | 4.66 | blastoderm | 2 | Hammerschmidt, M. | Development | 2001 | 128 | 849 | ||||||||||||||||
| Binding | acvr1 | neutral | bmp7 | OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. | bone | Endocrinology | 10610:06:00 | 2 | 21 | BMPR2-acvr1 | http://endo.endojournals.org/cgi/content/full/143/4/1423 | v143 i4 p1423 | urn:agi-Binding:inout-urn:agi-llid:90:inout-urn:agi-llid:655: | digtext:http://dev.biologists.org/cgi/reprint/128/6/849.pdf | url(http%3a//dev.biologists.org/cgi/reprint/128/6/849.pdf):pdf | ||||||||||||||
| Binding | bmp2a | neutral | bmp7 | This synergy is best explained by formation of BMP2/7 and 4/7 heterodimers. | bone | Cell Sci | 30643:07:00 | 2 | 22 | Zebrafish_Bmp2b_20080727 | http://jcs.biologists.org/cgi/content/full/117/7/1269 | v117 i7 p1269 | urn:agi-Binding:inout-urn:agi-llid:655:inout-urn:agi-llid:650: | digtext:http://dev.biologists.org/cgi/reprint/127/2/343.pdf | url(http%3a//dev.biologists.org/cgi/reprint/127/2/343.pdf):pdf | ||||||||||||||
| Expression | bmp4 | positive | bmp7 | bmp4 does not regulate the expression of itself or other BMPs bmp4 can activate its own expression in Xenopus overexpression experiments (Jones et al., 1992), and in zebrafish, both BMP2b and BMP7 are required for the maintenance of bmp2b, bmp7, and bmp4 | 2 | 4 | Zebrafish_Bmp2b_20080727 | urn:agi-Expression:inout-urn:agi-llid:652:out-urn:agi-llid:655::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=17727832&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)01214-6 | ||||||||||||||||||||
| Expression | bmp4 | negative | bmp7 | Because the expression of zebrafish bmp4 is delayed in comparison with the expression of bmp2b and bmp7 (Nikaido et al., 1997) and because no mutants in bmp4 were identified in any of the large-scale morphological screens, the role of bmp4 in zebrafish ha | 2 | 4 | Zebrafish_Bmp2b_20080727 | urn:agi-Expression:inout-urn:agi-llid:652:out-urn:agi-llid:655::negative | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=17727832&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)01214-6 | ||||||||||||||||||||
| Binding | bmp4 | neutral | bmp7 | This synergy is best explained by formation of BMP2/7 and 4/7 heterodimers. | egg | Cell Sci | 30643:07:00 | 2 | 52 | Zebrafish GRN from literatures-7-24-2008 | http://jcs.biologists.org/cgi/content/full/117/7/1269 | v117 i7 p1269 | urn:agi-Binding:inout-urn:agi-llid:655:inout-urn:agi-llid:652: | digtext:C:\Documents and Settings\yuh\My Documents\MedScan Reader Projects\zebrafish development\Tzu-Min's old papers\William S. Talbot 2005-1.pdf | url(C%3a%5cDocuments%20and%20Settings%5cyuh%5cMy%20Documents%5cMedScan%20Reader%20Projects%5czebrafish%20development%5cTzu-Min%27s%20old%20papers%5cWilliam%20S.%20Talbot%202005-1.pdf):pdf | ||||||||||||||
| Expression | fgf | neutral | bmp7 | Activating FGF signaling at the 512 cell stage results in an early decrease in bmp2, bmp4, and bmp7 expression at shield stage. | 2 | 2 | Zebrafish_Chordin_20080727 | urn:agi-Expression:inout-urn:agi-protfc:fibroblast%20growth%20factor:out-urn:agi-llid:655::unknown | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=15708554&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(04)00806-1 | ||||||||||||||||||||
| Expression | fgf | positive | bmp7 | Like XFD and ?-FGFR-4, early SU5402 FGF inhibition results in an increase in bmp2, bmp4, and bmp7 expression at late blastula and early gastrula stages (Fig. 6C). | 2 | 2 | Zebrafish_Chordin_20080727 | urn:agi-Expression:inout-urn:agi-protfc:fibroblast%20growth%20factor:out-urn:agi-llid:655::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=15708554&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(04)00806-1 | ||||||||||||||||||||
| Expression | fgf | negative | bmp7 | fgf3 was also found to be expressed in the early epiblast, and ongoing FGF signalling in epiblast cells was required for acquisition of neural fate and for the suppression of bmp4 and Bmp7 expression. | Genes & Dev | 53508:06:00 | 2 | 4 | Zebrafish_Chordin_20080727 | http://www.genesdev.org/cgi/content/full/12/7/1046 | v12 i7 p1046 | urn:agi-Expression:inout-urn:agi-protfc:fibroblast%20growth%20factor:out-urn:agi-llid:655::negative | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=15708554&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(04)00806-1 | ||||||||||||||||
| Expression | fgf24 | negative | bmp7 | Microinjection of fgf24 leads to inhibition of bmp7 expression at blastula stage. | overexpression | 4.66 | margin | 2 | Bernard Thisse | Development | 2004 | 131 | 2853 | ||||||||||||||||
| Expression | fgf3 | negative | bmp7 | Microinjection of fgf3 leads to inhibition of bmp7 expression at blastula stage. | overexpression | 4.66 | margin | 2 | Bernard Thisse | Development | 2004 | 131 | 2853 | ||||||||||||||||
| Expression | fgf8 | negative | bmp7 | fgf8 overexpression abolishes the blastula stage expression of bmp2b in the ventral blastoderm. | overexpression | 4.66 | margin | 2 | Bernard Thisse | Development | 2004 | 131 | 2853 | ||||||||||||||||
| Regulation | fsta | positive | bmp7 | Here, we report that during chick limb development Follistatin enhances BMP-7 action to induce muscle growth but prevents the ability of BMP-7 to induce apoptosis and muscle loss. | 2 | 6 | Zebrafish_Bmp2b_20080727 | urn:agi-Regulation:inout-urn:agi-llid:10468:out-urn:agi-llid:655::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=9882485&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S0012-1606(98)99003-0 | ||||||||||||||||||||
| Regulation | gpc3 | unknown | bmp7 | Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling. | 2 | 1 | Zebrafish_wnt5a_20080731 | urn:agi-Regulation:inout-urn:agi-llid:2719:out-urn:agi-llid:655::unknown | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=14610063&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14610063 | ||||||||||||||||||||
| Expression | isl1 | positive | bmp7 | Number of adrenergic and islet-1 immunoreactive cells is increased in avian trunk neural crest cultures in the presence of human recombinant osteogenic protein-1. | Mol. Cell. Biol | 64095:55:00 | 2 | 3 | Zebrafish_bmp4_20080727 | http://mcb.asm.org/cgi/content/full/25/12/5134 | v25 i12 p5134 | urn:agi-Expression:inout-urn:agi-llid:3670:out-urn:agi-llid:655::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3048&itool=AbstractPlus-def&uid=11640896&db=pubmed&url=http://linkinghub.elsevier.com/retrieve/pii/S1044-7431(01)91032-2 | ||||||||||||||||
| Expression | smad5 | positive | bmp7 | The sbn mutant displays severely reduced bmp2b staining | mutant embryos | 4.66 | margin | 1 | Matthias Hammerschmidt | Developmental Biology | 2002 | 250 | 263 | ||||||||||||||||
| Expression | smad5 | positive | bmp7 | Second, it has recently been reported that several null alleles of sbn / smad5 affect the initiation of bmp7 expression but have no effect on the initiation of bmp2b , which contrasts with the effects of rdratgMO ( 37 ). | PNAS | 18436:23:00 | 2 | 13 | Zebrafish_Bmp2b_20080727 | http://www.pnas.org/cgi/content/full/100/6/3315 | v100 i6 p3315 | urn:agi-Expression:inout-urn:agi-llid:4090:out-urn:agi-llid:655::positive | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=AbstractPlus-def&uid=16775002&db=pubmed&url=http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=16775002 | ||||||||||||||||
| Expression | smad5 | negative | bmp7 | Furthermore, embryos derived from females homozygous for null mutations in the smad5 locus exhibit reduced levels of the initial bmp7 and bmp2b expression (18, 19). | 2 | 4 | Zebrafish_Bmp2b_20080727 | urn:agi-Expression:inout-urn:agi-llid:4090:out-urn:agi-llid:655::negative | digtext:http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=AbstractPlus-nondef&uid=12682283&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12682283 | ||||||||||||||||||||