… and early preimplantation embryo: developmental changes in Sp1 and TATA box-binding protein, TBP - Full text - MIT Libraries
DM Worrad, PT Ram, RM Schultz - Development, 1994 - dev.biologists.org
... weight one. Cycloheximide inhibited the increase and the effect was more
pronounced for TBP than for Sp1 (Fig. 7); this difference ...
Cited by 74 - Web Search - dev.biologists.org - ncbi.nlm.nih.gov

Transcriptional autorepression of Msx1 gene is mediated by interactions of Msx1 protein with a multi … - Full text - MIT Libraries
S Shetty, T Takahashi, H Matsui, R Ayengar, R … - Biochem. J, 1999 - biochemj.org
... Finally, we demonstrate that Msx1 protein can be immunoprecipitated in
a multiprotein complex containing TBP, Sp1 and CBP\p300. ...
Cited by 13 - View as HTML - Web Search - biochemj.org - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov

[BOOK] Species-specific interaction of the glutamine-rich activation domains of Sp1 with the TATA-box …
ANJ Emili, J Greenblatt, CJ Ingles - 1994 - mcb.asm.org
... These activation domains of Sp1 also bind directly to Drosophila TBP but bind much
less strongly to TBP from the yeast Saccharomyces cerevisiae. ...
Cited by 91 - Web Search - pubmedcentral.nih.gov - ncbi.nlm.nih.gov - all 4 versions » - Get it from MIT Libraries - Library Search

… contains two activation domains: one that interacts with TBP and another that functions after TBP … - Full text - MIT Libraries
G Steger, J Ham, O Lefebvre, M Yaniv - J. Virol, 2004 - embojournal.npgjournals.com
... This block can be overcome by over-expression of human TATA binding protein (TBP)
or by the addition of either SP1 binding sites or an initiator element to the ...
Cited by 47 - Web Search - pubmedcentral.nih.gov - ncbi.nlm.nih.gov

Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription - Full text - MIT Libraries
TP Spann, AE Goldman, C Wang, S Huang, RD Goldman - J. Cell Biol, 2002 - intl.jcb.org
... antigen (B'' and Y12; 1:50, 1:20; gifts from D. Spector, Cold Spring Harbor Laboratory,
Cold Spring Harbor, NY), TBP, Sp1 (SC 273 and SC 59; 1:30; Santa Cruz ...
Cited by 47 - Web Search - goldmanlab.northwestern.edu - ibmb.uni.wroc.pl - dx.doi.org - all 6 versions »

Evidence for functional binding and stable sliding of the TATA binding protein on nonspecific DNA. - Full text - MIT Libraries
RA Coleman, BF Pugh - J Biol Chem, 1995 - jbc.org
... For the filter binding and EMSA experiments where formation of a complex between
the protein (in this case, TBP or Sp1) and radiolabeled DNA was being measured ...
Cited by 42 - Web Search - jbc.org - ncbi.nlm.nih.gov

Assembly of recombinant TFIID reveals differential coactivator requirements for distinct …
JL Chen, LD Attardi, CP Verrijzer, K Yokomori, R … - Cell, 1994 - ncbi.nlm.nih.gov
... The activator NTF-1, which binds TAFII150, stimulates transcription with a complex
containing only TBP, TAFII250, and TAFII150, whereas Sp1 binds and ...
Cited by 205 - Web Search - ncbi.nlm.nih.gov - Get it from MIT Libraries

Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice - Full text - MIT Libraries
ZX Yu, SH Li, HP Nguyen, XJ Li - Human Molecular Genetics, 2002 - hmg.oupjournals.org
... investigated. We examined three important transcription factors – CBP,
TBP and Sp1 – in various HD mouse models. Our findings ...
Cited by 30 - Web Search - hmg.oupjournals.org - ingentaconnect.com - ncbi.nlm.nih.gov - all 6 versions »

Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA - Full text - MIT Libraries
M Bonfanti, E La Valle, JMFS Faro, G Faircloth, G … - Anti-Cancer Drug Design, 1999 - ingentaconnect.com
... transcriptional activators regulated during the cell cycle (E2F) or growth stimulation
by serum (SRF); and (iii) general transcription factors (TBP, Sp1 and NF ...
Cited by 31 - Web Search - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov

The glutamine-rich activation domains of human Sp1 do not stimulate transcription in Saccharomyces … - Full text - MIT Libraries
AS Ponticelli, TS Pardee, K Struhl - Mol. Cell. Biol, 1995 - mcb.asm.org
... 986 PONTICELLI ET AL. M OL . C ELL . B IOL . Page 5. yeast TBP hybrids
along with Sp1 did not result in Sp1 activa- tion of his3. ...
Cited by 35 - Web Search - pubmedcentral.nih.gov - mcb.asm.org - ncbi.nlm.nih.gov

Herpes simplex virus infected cell polypeptide 4 preferentially represses Sp1-activated over basal … - Full text - MIT Libraries
B Gu, R Rivera-Gonzalez, CA Smith, NA DeLuca - Proc Natl Acad Sci US A, 1993 - pubmedcentral.nih.gov
... transcription factors from HeLa cell nuclear extracts, recombinant TATA binding
protein (TBP) and TFIIB, and the transcriptional activator Sp1 to reconstitute ...
Cited by 20 - Web Search - pnas.org - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov

Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits …
G Lyss, TJ Schmidt, I Merfort, HL Pahl - Biol Chem, 1997 - ncbi.nlm.nih.gov
... This inhibition is selective, as the activity of four other transcription
factors, Oct-1, TBP, Sp1 and STAT 5 was not affected. ...
Cited by 38 - Web Search - Get it from MIT Libraries

Sp1 Transcription Factor Is Required for In Vitro Basal and Tat-Activated Transcription from the … - Full text - MIT Libraries
S CARLOS, A MARIANO - Journal OF Virology, 1995 - jvi.asm.org
... FIG. 3. Chromatographic separation of Sp1 and TBP. Forty micrograms of
unfractionated HeLa cell nuclear extract (NE; lane 1), 40 ...
Cited by 30 - Web Search - pubmedcentral.nih.gov - jvi.asm.org - ncbi.nlm.nih.gov

Adeno-associated virus major Rep78 protein disrupts binding of TATA-binding protein to the p97 … - Full text - MIT Libraries
PF Su, SY Chiang, CW Wu, FY Wu - J. Virol, 2000 - jvi.asm.org
... Since Rep78 is known to interact with both TBP and Sp1 (16, 17), the question of
whether Rep78 is able to interfere with the binding of TBP to the TATA box of ...
Cited by 10 - Web Search - pubmedcentral.nih.gov - jvi.asm.org - ncbi.nlm.nih.gov

Different mechanisms contribute to the E2-mediated transcriptional repression of human … - Full text - MIT Libraries
C Demeret, C Desaintes, M Yaniv, F Thierry - J. Virol, 1997 - jvi.asm.org
... Binding of E2 to the two promoter-proximal E2 recognition elements (E2 BS 1 and
2) displaces TBP and Sp1 from their binding sites (6, 8, 9, 35). ...
Cited by 24 - Web Search - milkpa.idv.tw - pubmedcentral.nih.gov - ncbi.nlm.nih.gov - all 7 versions »

… by poliovirus: a virus-encoded protease (3Cpro) inhibits formation of TBP-TATA box complex in vitro - Full text - MIT Libraries
P Yalamanchili, K Harris, E Wimmer, A Dasgupta - J. Virol, 1996 - jvi.asm.org
... in mock-infected cell was stimulated twofold by ad- dition of TBP, suggesting that
TBP was limiting in mock- infected extract for Sp1-activated transcription ...
Cited by 31 - Web Search - pubmedcentral.nih.gov - jvi.asm.org - ncbi.nlm.nih.gov

Low pH enhances Sp 1 DNA binding activity and interaction with TBP - Full text - MIT Libraries
T Torigoe, H Izumi, Y Yoshida, H Ishiguchi, T … - Nucleic Acids Research, 2003 - nar.oupjournals.org
... Furthermore, we also found that there are some differences in the interaction of
TBP with Sp1 and Sp3 under neutral to alkaline conditions (Fig. ...
Cited by 5 - Web Search - pubmedcentral.nih.gov - ingentaconnect.com - ncbi.nlm.nih.gov - all 7 versions »

Huntingtin-protein interactions and the pathogenesis of Huntington's disease
SH Li, XJ Li - Trends Genet, 2004 - lifesci.sussex.ac.uk
... were unable to find nuclear htt inclusions containing CBP, TBP or SP1, or a significant
decrease in the cellular level of these transcription factors [38]. ...
Cited by 16 - View as HTML - Web Search - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov - Get it from MIT Libraries

TBP binding and the rate of transcription initiation from the human beta-globin gene - Full text - MIT Libraries
M Antoniou, E de Boer, E Spanopoulou, A Imam, F … - Nucleic Acids Res, 1995 - pubmedcentral.nih.gov
... binding over the TATA box and the region of transcription initiation (cap) site
of the human beta-globin promoter; TATA binding protein TBP at -30, Sp1 at -19 ...
Cited by 9 - Web Search - nar.oupjournals.org - ep.eur.nl - dspace.ubib.eur.nl - all 7 versions »

Stepwise recruitment of components of the preinitiation complex by upstream activators in vivo - Full text - MIT Libraries
S He, SJ Weintraub - Mol. Cell. Biol, 1998 - mcb.asm.org
... First, we demonstrated that overexpression of TBP reduces the activity of
promoter-bound TBP and Sp1 but potentiates the activity of VP16 456. ...
Cited by 8 - Web Search - pubmedcentral.nih.gov - mcb.asm.org - ncbi.nlm.nih.gov

Quantitation of RNA polymerase II and its transcription factors in an HeLa cell: little soluble … - Full text - MIT Libraries
H Kimura, Y Tao, RG Roeder, PR Cook - Mol. Cell. Biol, 1999 - mcb.asm.org
... In contrast, TBP and Sp1 proved very sensitive, with >40% being detached by the
lowest concentration of HaeIII used; they appear to be detached much like ...
Cited by 43 - Web Search - mcb.asm.org - pubmedcentral.nih.gov - ncbi.nlm.nih.gov

Sp1 activation of a TATA-less promoter requires a species-specific interaction involving … - Full text - MIT Libraries
KH Emami, TW Burke, ST Smale - J. Biol. Chem, 2005 - nar.oupjournals.org
... Physical interactions have been detected between Sp1 and three components
of human TFIID: TBP, hTAF II 130 and hTAF II 55 (9,20-23). ...
Cited by 20 - Web Search - pubmedcentral.nih.gov - ingentaconnect.com - ncbi.nlm.nih.gov - all 6 versions »

Drosophila head segmentation factor Buttonhead interacts with the same TATA box-binding protein- … - Full text - MIT Libraries
F Schoeck, F Sauer, H Jaeckle, BA Purnell - Developmental Biology, 1999 - pnas.org
... which were programmed with the reporter plasmid (GC) 3 BCAT (12) and either Sp1
(lanes 2 and 6) or BTD (lanes 4 and 8). TBP was unable to mediate Sp1- and BTD ...
Cited by 6 - Web Search - pubmedcentral.nih.gov - dx.doi.org - ncbi.nlm.nih.gov - all 6 versions »

Transforming growth factor activates the promoter of cyclin-dependent kinase inhibitor p15 INK4B … - Full text - MIT Libraries
JM Li, MA Nichols, S Chandrasekharan, Y Xiong, XF … - J Biol Chem, 1995 - jbc.org
... presumably through its interaction with the TBP-associated factor 110 (TAF II 110)
(19). Recent studies suggest that Sp1 and a member of the Sp1 family, Sp3 ...
Cited by 98 - Web Search - ncbi.nlm.nih.gov

A Glutamine-Rich Hydrophobic Patch in Transcription Factor Sp1 Contacts the dTAF 11 110 Component of … - Full text - MIT Libraries
G Gill, E Pascal, ZH Tseng, R Tjian - Proceedings of the National Academy of Sciences - pnas.org
... of transcription by the promoter-specific factor Sp1 requires coactivators that
are tightly associated with the TATA-box-binding protein (TBP) in the TFIID ...
Cited by 240 - Web Search - pnas.org - pubmedcentral.nih.gov - ncbi.nlm.nih.gov - all 5 versions »

Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene … - Full text - MIT Libraries
AM Moilanen, H Poukka, U Karvonen, M Hakli, OA … - Mol Cell Biol, 1998 - mcb.asm.org
... We also compared activities of some simple promoter constructs containing binding
sites for TBP, Sp1, and AP1 in the absence or presence of coexpressed SNURF. ...
Cited by 88 - Web Search - mcb.asm.org - pubmedcentral.nih.gov - ncbi.nlm.nih.gov - all 5 versions »

Regulation of Transcription by Multisubunit Complexes That Alter Nucleosome Structure
DJ STEGER, RT UTLEY, PA GRANT, S JOHN, A … - Cold Spring Harbor Symposia on Quantitative Biology, 1998 - dx.doi.org
... DNase I digestion patterns of nucleosome core particles and stimulate the binding
of a diverse set of activators including GAL4 derivatives, TBP, Sp1, NF-κB ...
Cited by 3 - Web Search - cshl-symposium.org - cshl-symposium.org - ncbi.nlm.nih.gov - Get it from MIT Libraries

Cooperativity in vivo between the E2 transactivator and the TATA box binding protein depends on core … - Full text - MIT Libraries
J Ham, G Steger, M Yaniv - Mol. Cell. Biol, 2004 - embojournal.npgjournals.com
... Since either TBP overexpression or the presence of an initiator or SP1 binding sites
can increase activation by E2, it seems likely that the principal role of ...
Cited by 39 - Web Search - pubmedcentral.nih.gov - ncbi.nlm.nih.gov

The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein … - Full text - MIT Libraries
S Ryu, S Zhou, AG Ladurner, R Tjian - Nature, 1999 - nature.com
... Drosophila TFIIA directs cooperative DNA binding with TBP and mediates transcriptional ...
coactivator are required for synergistic activation by Sp1 and SREBP in ...
Cited by 153 - Web Search - nature.com - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov

Mechanism of initiator-mediated transcription: evidence for a functional interaction between the … - Full text - MIT Libraries
B Zenzie-Gregory, A Khachi, IP Garraway, ST Smale - Mol. Cell. Biol, 1993 - mcb.asm.org
... We have begun to address the role of TBP during transcription from Sp1-initiator
promoters by varying the nucleotide sequence between -14 and -33 relative to ...
Cited by 34 - Web Search - pubmedcentral.nih.gov - ncbi.nlm.nih.gov

Cofactor Requirements for Transcriptional Activation by Sp1
AM Naeaer, S Ryu, R Tjian - Cold Spring Harb Symp Quant Biol, 1998 - dx.doi.org
... that CRSP is dis- tinct from other cofactors that have been isolated (ie, PC4, CBP,
SAGA, etc.) and that activation by Sp1 re- quires both TBP/TAFs and CRSP ...
Cited by 16 - Web Search - cshl-symposium.org - cshl-symposium.org - ncbi.nlm.nih.gov - Get it from MIT Libraries

Transcriptional Activation by SP1 as Directed Through TATA or Initiator: Specific Requirement for … - Full text - MIT Libraries
ST Smale, MC Schmidt, AJ Berk, D Baltimore - Proceedings of the National Academy of Sciences - pnas.org
... page S. Kudo Methyl-CpG-Binding Protein MeCP2 Represses Sp1-Activated Transcription
of ... P. De Luca, and L. Lania Recruitment of Human TBP Selectively Activates ...
Cited by 129 - Web Search - pubmedcentral.nih.gov - ncbi.nlm.nih.gov - adsabs.harvard.edu

Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators - Full text - MIT Libraries
CM Chiang, RG Roeder - Science, 1995 - ncbi.nlm.nih.gov
... comprised of the TATA-binding protein (TBP) and multiple TBP-associated factors ... through
its central region and with multiple activators--including Sp1, YY1, USF ...
Cited by 198 - Web Search - ncbi.nlm.nih.gov

FMGA: finding motifs by genetic algorithm
FFM Liu, JJP Tsai, RM Chen, SN Chen, SH Shih - Bioinformatics and Bioengineering, 2004. BIBE 2004. …, 2004 - ieeexplore.ieee.org
... the DNA transcription. Besides TBP and Sp1 factors, there are also other
factors to aid the DNA transcription. Many of the regulatory ...
Cited by 1 - Web Search - doi.ieeecomputersociety.org - ieeexplore.ieee.org

… Drosophila transcription factor IID directs assembly of a complex containing TBP and a coactivator - Full text - MIT Libraries
ROJ Weinzierl, BD Dynlacht, R Tjian - Nature, 1993 - nature.com
... TAF II 250. This triple complex supports Sp1 activation and reveals specific
interactions between TAF II 250, TBP and TAF II 110. ...
Cited by 52 - Web Search - nature.com - ncbi.nlm.nih.gov

Regional and temporal specialization in the nucleus: a transcriptionally-active nuclear domain rich … - Full text - MIT Libraries
A Pombo, P Cuello, W Schul, JB Yoon, RG Roeder, PR … - The EMBO Journal, 1998 - embojournal.npgjournals.com
... Oct1, a transcription factor that interacts with PTF, is also enriched in these
domains; RNA polymerase II, TBP and Sp1 are also present. ...
Cited by 49 - Web Search - emboj.org - wwwlib.bionet.nsc.ru - ncbi.nlm.nih.gov - all 6 versions »

Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T … - Full text - MIT Libraries
J Vlach, A Garcia, JM Jacque, MS Rodriguez, S … - Virology, 1995 - ncbi.nlm.nih.gov
... constructs in lymphoblastoid cells stimulated by OKA depended on both functional
Sp1 binding elements and the ability of the TATA box to bind the protein TBP. ...
Cited by 39 - Web Search

hnRNP U inhibits carboxy-terminal domain phosphorylation by TFIIH and represses RNA polymerase II … - Full text - MIT Libraries
MK Kim, VM Nikodem - Mol. Cell. Biol, 1999 - mcb.asm.org
... As previously reported (9, 28), however, transcription factors such as TBP, Sp1
(Fig. 3A), and TFIIB or Oct-1 (data not shown) were not detected. ...
Cited by 19 - Web Search - pubmedcentral.nih.gov - mcb.asm.org - ncbi.nlm.nih.gov

Drosophila TFIIA directs cooperative DNA binding with TBP and mediates transcriptional activation
K Yokomori, MP Zeidler, JL Chen, CP Verrijzer, M … - Genes Dev, 1994 - genesdev.org
... The dTFIIA-L/S complex also binds cooperatively with TBP to TATA ... enhance transcriptional
activation by upstream transcription factors including Sp1, VP16, and ...
Cited by 50 - Web Search - ncbi.nlm.nih.gov - Get it from MIT Libraries

Transcription factors as targets for DNA-interacting drugs
M Gniazdowski, WA Denny, SM Nelson, M Czyz - Curr. Med. Chem, 2003 - ingentaconnect.com
... (B) Some drugs which inhibit transcription: distamycin A (DST) and actinomycin D
do not allow TBP and Sp1 to interact with their binding sites [21,44]. ...
Cited by 6 - Web Search - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov - Get it from MIT Libraries

MDM2: life without p53
S Daujat, H Neel, J Piette - Trends Genet, 2001 - bio.kaist.ac.kr
... ID1 ID2 pRb Numb E2F1 ARF NoLS MTBP TAFII 250 TBP L5 Sp1 Fig. 1. The MDM2 oncoprotein.
Domains of MDM2 that interact with proteins discussed in the text. ...
Cited by 40 - View as HTML - Web Search - ingentaconnect.com - ncbi.nlm.nih.gov - Get it from MIT Libraries

Identification of Limiting Steps for Efficient Trans-activation of HIV-1 Promoter by Tat in … - Full text - MIT Libraries
L Daviet, F Bois, PL Battisti, A Gatignol - J Biol Chem, 1998 - jbc.org
... active? This lack of Sp1 function is not due to an absence of interaction
with TBP as yeast TBP mediates Sp1 activity (81). Recently ...
Cited by 3 - Web Search - jbc.org - ncbi.nlm.nih.gov

Cytosine Methylation Does not Affect Binding of Transcription Factor Sp1 - Full text - MIT Libraries
MA Harrington, PA Jones, M Imagawa, M Karin - J. Virol, 2004 - pnas.org
... Torigoe, H. Izumi, Y. Yoshida, H. Ishiguchi, T. Okamoto, H. Itoh, and K. Kohno Low
pH enhances Sp1 DNA binding activity and interaction with TBP Nucleic Acids ...
Cited by 41 - Web Search - pubmedcentral.nih.gov - ncbi.nlm.nih.gov

Transcriptional repression by p 53 involves molecular interactions distinct from those with the TATA … - Full text - MIT Libraries
G Farmer, P Friedlander, J Colgan, JL Manley, C … - Nucleic Acids Research, 1996 - nar.oupjournals.org
... also inhibited TATA-dependent transcription activated by Sp1. However, p53 was unable
to repress a basal TATA promoter stimulated by overexpression of TBP. ...
Cited by 38 - Web Search - nar.oupjournals.org - pubmedcentral.nih.gov - ncbi.nlm.nih.gov

… RNA-polymerase II and N-terminal segment of the human TATA binding protein (TBP) can mediate remote … - Full text - MIT Libraries
K Seipel, O Georgiev, HP Gerber, W Schaffner - Nucleic Acids Res, 1993 - pubmedcentral.nih.gov
... exemplified by the glutamine-rich activation domains of Oct and Sp1 factors, mediates ...
The human TATA-binding protein (TBP) contains at its N-terminus a domain ...
Cited by 10 - Web Search - nar.oupjournals.org - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov

Artificial Recruitment of Sp1 or TBP Can Replace the Role of IE1 in the Synergistic Transactivation … - Full text - MIT Libraries
JM Kim, Y Hong, S Kim - Biochemical and Biophysical Research Communications, 2000 - ingentaconnect.com
... Artificial Recruitment of Sp1 or TBP Can Replace the Role of IE1 in the Synergistic
Transactivation by IE1 and IE2. Authors: Kim JM; Hong Y.; Kim S. ...
Web Search - ncbi.nlm.nih.gov - ncbi.nlm.nih.gov

Incorporation of D osophila TAF110 into the yeast TFIID complex does not permit the Sp1 glutamine- …
M Keaveney, K Struhl - genestocellsonline.org
... The failure of the TAF110-TBP fusions to mediate Sp1-dependent activation could
be explained by a failure to form functional TFIID complexes due to competition ...
Web Search - ingentaconnect.com

Transcriptional trans Activation by Human Immunodeficiency Virus Type 1 Tat Requires Specific …
S CARLOS, A MARIANO - Journal OF Virology, 1995 - jvi.asm.org
... The transcriptional factors TBP and Sp1 have been impli- cated in basal
and Tat-dependent transcriptional activation (35, 39). The ...
Web Search - Get it from MIT Libraries

Functional interaction between p53, the TATA-binding protein (TBP), and TBP-associated factors in … - Full text - MIT Libraries
G Farmer, J Colgan, Y Nakatani, JL Manley, C … - Mol. Cell. Biol, 1996 - mcb.asm.org
... cells do not express any known version of p53 (53); second, TBP can be ... E1B-CAT;
similarly, when it was transfected with a plasmid expressing Sp1, syner- gistic ...
Cited by 53 - Web Search - mcb.asm.org - pubmedcentral.nih.gov - ncbi.nlm.nih.gov - all 5 versions »

Recruitment of Human TBP Selectively Activates RNA Polymerase II TATA-dependent Promoters - Full text - MIT Libraries
B Majello, G Napolitano, P De Luca, L Lania - J Biol Chem, 1998 - jbc.org
... glutamine-rich domains of Sp1 and Sp3 inhibit the GAL4-hTBP activity, suggesting
that these domains function in vivo by accelerating the binding of TBP to the ...
Cited by 20 - Web Search - jbc.org - ncbi.nlm.nih.gov