TY - JOUR AU - Wang, G. L. AU - Jiang, B. -. H. AU - Rue, E. A. AU - Semenza, G. L. PY - 1995 DA - 1995// TI - Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension JO - Proc Natl Acad Sci USA VL - 92 UR - https://doi.org/10.1073/pnas.92.12.5510 DO - 10.1073/pnas.92.12.5510 ID - Wang1995 ER - TY - JOUR AU - Semenza, G. L. PY - 2001 DA - 2001// TI - Hypoxia-inducible factor-1: oxygen homeostasis and disease pathophysiology JO - Trends Mol Med VL - 8 UR - https://doi.org/10.1016/S1471-4914(01)02090-1 DO - 10.1016/S1471-4914(01)02090-1 ID - Semenza2001 ER - TY - STD TI - Metzen E, Ratcliffe PJ: HIF-hydroxylation and cellular oxygen sensing. Biol Chem. 2004, 223-230. 10.1515/BC.2004.016. 3–4 ID - ref3 ER - TY - JOUR AU - Semenza, G. L. PY - 1998 DA - 1998// TI - Hypoxia-inducible factor1: master regulator of O2homeostasis JO - Curr Opin Gen Dev VL - 8 UR - https://doi.org/10.1016/S0959-437X(98)80016-6 DO - 10.1016/S0959-437X(98)80016-6 ID - Semenza1998 ER - TY - JOUR AU - Brunelle, J. K. AU - Santore, M. T. AU - Budinger, G. R. AU - Tang, Y. AU - Barret, T. A. AU - Zong, W. X. AU - Kandel, E. AU - Keith, B. AU - Simon, C. AU - Thompson, C. B. AU - Hay, N. AU - Chandel, N. S. PY - 2004 DA - 2004// TI - C-Myc sensitization to oxygen deprivation-induced cell death is dependent on Bax/Bak, but is independent of p53 and hypoxia inducible factor-1 JO - J Biol Chem VL - 279 UR - https://doi.org/10.1074/jbc.M312241200 DO - 10.1074/jbc.M312241200 ID - Brunelle2004 ER - TY - JOUR AU - McClintock, D. S. AU - Santore, M. T. AU - Lee, V. Y. AU - Brunelle, J. AU - Budinger, G. R. AU - Zong, W. X. AU - Thompson, C. B. AU - Hay, N. AU - Chandel, N. S. PY - 2002 DA - 2002// TI - Bcl-2 family members and functional electron transport chain regulate oxygen deprivation-induced cell death JO - Mol Cell Biol VL - 22 UR - https://doi.org/10.1128/MCB.22.1.94-104.2002 DO - 10.1128/MCB.22.1.94-104.2002 ID - McClintock2002 ER - TY - JOUR AU - Yamamoto, K. AU - Tomita, N. AU - Yoshimura, S. AU - Nakagami, H. AU - Taniyama, Y. AU - Yamasaki, K. AU - Ogihara, T. AU - Morishita, R. PY - 2004 DA - 2004// TI - Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury JO - Int J Mol Med VL - 14 ID - Yamamoto2004 ER - TY - JOUR AU - Marin-Garcia, J. AU - Goldenthal, M. J. PY - 2004 DA - 2004// TI - Heart mitochondria signaling pathways: appraisal of an emerging field JO - J Mol Med VL - 82 UR - https://doi.org/10.1007/s00109-004-0567-7 DO - 10.1007/s00109-004-0567-7 ID - Marin-Garcia2004 ER - TY - JOUR AU - Carmeliet, P. AU - Dor, Y. AU - Herbert, J. -. M. AU - Fukumara, D. AU - Brusselmans, K. AU - Dewerchin, M. AU - Neeman, M. AU - Bono, F. AU - Abramovitch, R. AU - Maxwell, P. AU - Koch, C. J. AU - Ratcliffe, P. AU - Moons, L. AU - Jain, R. K. AU - Collen, D. AU - Keshet, E. PY - 1998 DA - 1998// TI - Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumor angiogenesis JO - Nature VL - 394 UR - https://doi.org/10.1038/28867 DO - 10.1038/28867 ID - Carmeliet1998 ER - TY - JOUR AU - Krick, S. AU - Eul, B. G. AU - Hanze, J. AU - Savai, R. AU - Grimminger, F. AU - Seeger, W. AU - Rose, F. PY - 2005 DA - 2005// TI - Role of hypoxia-inducible factor-1alpha in hypoxia-induced apoptosis of primary alveolar epithelial type II cells JO - Am J Respir Cell Mol Biol VL - 32 UR - https://doi.org/10.1165/rcmb.2004-0314OC DO - 10.1165/rcmb.2004-0314OC ID - Krick2005 ER - TY - JOUR AU - Graham, R. M. AU - Frazier, D. P. AU - Thompson, J. W. AU - Haliko, S. AU - Li, H. AU - Wasserlauf, B. J. AU - Spiga, M. G. AU - Bishopric, N. H. AU - Webster, K. A. PY - 2004 DA - 2004// TI - A unique pathway of cardiac myocyte death caused by hypoxia-acidosis JO - J Exp Biol VL - 207 UR - https://doi.org/10.1242/jeb.01109 DO - 10.1242/jeb.01109 ID - Graham2004 ER - TY - JOUR AU - Piret, J. P. AU - Mottet, D. AU - Raes, M. AU - Michiels, C. PY - 2002 DA - 2002// TI - Is HIF-1alpha a pro- or an anti-apoptotic protein? JO - Biochem Pharmacol VL - 64 UR - https://doi.org/10.1016/S0006-2952(02)01155-3 DO - 10.1016/S0006-2952(02)01155-3 ID - Piret2002 ER - TY - JOUR AU - Greijer, A. E. AU - Wall, E. v. a. n. d. e. r. PY - 2004 DA - 2004// TI - The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis JO - J Clin Pathol VL - 57 UR - https://doi.org/10.1136/jcp.2003.015032 DO - 10.1136/jcp.2003.015032 ID - Greijer2004 ER - TY - JOUR AU - Bruick, R. K. PY - 2000 DA - 2000// TI - Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia JO - Proc Natl Acad Sci USA VL - 97 UR - https://doi.org/10.1073/pnas.97.16.9082 DO - 10.1073/pnas.97.16.9082 ID - Bruick2000 ER - TY - JOUR AU - Akakura, N. AU - Kobayashi, M. AU - Horiuchi, I. AU - Suzuki, A. AU - Wang, J. AU - Chen, J. AU - Niizeki, H. AU - Kawamura, K. i. AU - Hosokawa, M. AU - Asaka, M. PY - 2001 DA - 2001// TI - Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation JO - Cancer Res VL - 61 ID - Akakura2001 ER - TY - JOUR AU - Erler, J. T. AU - Cawthorne, C. J. AU - Williams, K. J. AU - Koritzinsky, M. AU - Wouters, B. G. AU - Wilson, C. AU - Miller, C. AU - Demonacos, C. AU - Stratford, I. J. AU - Dive, C. PY - 2004 DA - 2004// TI - Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance JO - Mol Cell Biol VL - 24 UR - https://doi.org/10.1128/MCB.24.7.2875-2889.2004 DO - 10.1128/MCB.24.7.2875-2889.2004 ID - Erler2004 ER - TY - JOUR AU - Chen, J. AU - Zhao, S. AU - Nakada, K. AU - Kuge, Y. AU - Tamaki, N. AU - Okada, F. AU - Wang, J. AU - Shindo, M. AU - Higashino, F. AU - Takeda, K. AU - Asaka, M. AU - Katoh, H. AU - Sugiyama, T. AU - Hosokawa, M. AU - Kobayashi, M. PY - 2003 DA - 2003// TI - Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism JO - Am J Pathol VL - 162 UR - https://doi.org/10.1016/S0002-9440(10)63924-7 DO - 10.1016/S0002-9440(10)63924-7 ID - Chen2003 ER - TY - JOUR AU - Piret, J. -. P. AU - Mottet, D. AU - Raes, M. AU - Michiels, C. PY - 2002 DA - 2002// TI - CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2 JO - Ann NY Acad Sci VL - 973 UR - https://doi.org/10.1111/j.1749-6632.2002.tb04680.x DO - 10.1111/j.1749-6632.2002.tb04680.x ID - Piret2002 ER - TY - JOUR AU - Dai, S. AU - Huang, M. L. AU - Hsu, C. Y. Y. AU - Clifford Chao, K. S. PY - 2003 DA - 2003// TI - Inhibition of hypoxia inducible factor 1 alpha causes oxygen-independent cytotoxicity and induces p53 independent apoptosis in glioblastoma cells JO - Int J Radiat Oncol Biol Phys VL - 55 UR - https://doi.org/10.1016/S0360-3016(02)04507-8 DO - 10.1016/S0360-3016(02)04507-8 ID - Dai2003 ER - TY - JOUR AU - Malhotra, R. AU - Brosius, F. C. PY - 1999 DA - 1999// TI - Glucose uptake and glycolysis reduce hypoxia-induced apoptosis in cultured cardiac myocytes JO - J Biol Chem VL - 274 UR - https://doi.org/10.1074/jbc.274.18.12567 DO - 10.1074/jbc.274.18.12567 ID - Malhotra1999 ER - TY - JOUR AU - Lin, Z. AU - Malhotra, R. AU - Weinberg, J. M. AU - Merritt, S. AU - Holzman, L. B. AU - Brosius, F. C. PY - 2000 DA - 2000// TI - Increased GLUT1 expression prevents hypoxia-induced apoptosis and cJun-NH2-terminal kinase activation in vascular smooth muscle cells JO - Am J Physiol VL - 278 ID - Lin2000 ER - TY - JOUR AU - Loberg, R. D. AU - Vesely, E. AU - Brosius, F. C. PY - 2002 DA - 2002// TI - Enhanced glycogen synthase kinase-3β activity mediates hypoxia-induced apoptosis of vascular smooth muscle cells and is prevented by glucose transport and metabolism JO - J Biol Chem VL - 277 UR - https://doi.org/10.1074/jbc.M206405200 DO - 10.1074/jbc.M206405200 ID - Loberg2002 ER - TY - JOUR AU - Malhotra, R. AU - Tyson, D. G. W. AU - Sone, H. AU - Aoki, K. AU - Kumagai, A. K. AU - Brosius, F. C. PY - 2002 DA - 2002// TI - Glucose uptake and adenoviral mediated GLUT1 infection decrease hypoxia-induced HIF-1a levels in cardiac myocytes JO - J Mol Cell Cardiol VL - 34 UR - https://doi.org/10.1006/jmcc.2002.2047 DO - 10.1006/jmcc.2002.2047 ID - Malhotra2002 ER - TY - JOUR AU - Gao, W. AU - Ferguson, G. AU - Connell, P. AU - Walshe, T. AU - Murphy, R. AU - Birney, Y. A. AU - O'brien, C. AU - Cahill, P. A. PY - 2007 DA - 2007// TI - High glucose concentrations alter hypoxia-induced control of vascular smooth muscle cell growth via a HIF-1alpha-dependent pathway JO - J Mol Cell Cardiol VL - 42 UR - https://doi.org/10.1016/j.yjmcc.2006.12.006 DO - 10.1016/j.yjmcc.2006.12.006 ID - Gao2007 ER - TY - JOUR AU - Jiang, B. -. H. AU - Rue, E. AU - Wang, G. L. AU - Roe, R. AU - Semenza, G. L. PY - 1996 DA - 1996// TI - Dimerization, DNA binding, and transactivation properties of hypoxia inducible factor 1 JO - J Biol Chem VL - 271 UR - https://doi.org/10.1074/jbc.271.30.17771 DO - 10.1074/jbc.271.30.17771 ID - Jiang1996 ER - TY - JOUR AU - Reynolds, A. AU - Leake, D. AU - Boese, Q. AU - Scaringe, S. AU - Marshall, W. S. AU - Khvorova, A. PY - 2004 DA - 2004// TI - Rational siRNA design for RNA interference JO - Nature Biotechnology VL - 22 UR - https://doi.org/10.1038/nbt936 DO - 10.1038/nbt936 ID - Reynolds2004 ER - TY - JOUR AU - Hsu, Y. T. AU - Wolter, K. G. AU - Youle, R. J. PY - 1997 DA - 1997// TI - Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis JO - Proc Natl Acad Sci USA VL - 94 UR - https://doi.org/10.1073/pnas.94.8.3668 DO - 10.1073/pnas.94.8.3668 ID - Hsu1997 ER - TY - JOUR AU - Van Hoecke, M. AU - Prigent-Tessier, A. S. AU - Garnier, P. E. AU - Bertrand, N. M. AU - Filomenko, R. AU - Bettaieb, A. AU - Marie, C. AU - Beley, A. G. PY - 2007 DA - 2007// TI - Evidence of HIF-1 functional binding activity to caspase-3 promoter after photothrombotic cerebral ischemia JO - Mol Cell Neurosci VL - 34 UR - https://doi.org/10.1016/j.mcn.2006.09.009 DO - 10.1016/j.mcn.2006.09.009 ID - Van Hoecke2007 ER - TY - JOUR AU - Sowter, H. M. AU - Ratcliffe, P. J. AU - Watson, P. AU - Greenberg, A. H. AU - Harris, A. L. PY - 2001 DA - 2001// TI - HIF-1- dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors JO - Cancer Res VL - 61 ID - Sowter2001 ER - TY - JOUR AU - Bruick, R. K. PY - 2000 DA - 2000// TI - Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia JO - Proc Natl Acad Sci USA VL - 97 UR - https://doi.org/10.1073/pnas.97.16.9082 DO - 10.1073/pnas.97.16.9082 ID - Bruick2000 ER - TY - JOUR AU - An, W. G. AU - Kanekal, M. AU - Simon, M. C. AU - Maltepe, E. AU - Blagosklonny, M. V. PY - 1998 DA - 1998// TI - Stabilization of wild-type p53 by hypoxia-inducible factor 1α JO - Nature VL - 392 UR - https://doi.org/10.1038/32925 DO - 10.1038/32925 ID - An1998 ER - TY - JOUR AU - Wright, G. AU - Higgins, J. J. AU - Raines, R. T. AU - Steenberger, C. AU - Murphy, E. PY - 2003 DA - 2003// TI - Activation of the prolyl hydroxylase oxygen-sensor results in induction of GLUT 1, heme oxygenase -1, and nitric-oxide synthase proteins and confers protection from metabolic inhibition to cardiomyocytes JO - J Biol Chem VL - 278 UR - https://doi.org/10.1074/jbc.M301391200 DO - 10.1074/jbc.M301391200 ID - Wright2003 ER - TY - JOUR AU - Date, T. AU - Mochizuki, S. AU - Belanger, A. J. AU - Yamakawa, M. AU - Luo, Z. AU - Vincent, K. A. AU - Cheng, S. H. AU - Gregory, R. J. AU - Jiang, C. PY - 2005 DA - 2005// TI - Expression of constitutively stable hybrid hypoxia-inducible factor-1 alpha protects cultured rat cardiomyoctes against simulated ischemia-reperfusion injury JO - Am J Physiol Cell Physiol VL - 288 UR - https://doi.org/10.1152/ajpcell.00374.2004 DO - 10.1152/ajpcell.00374.2004 ID - Date2005 ER - TY - JOUR AU - Natarajan, R. AU - Salloum, F. N. AU - Fisher, B. J. AU - Kukreja, R. C. AU - Fowler, A. A. PY - 2006 DA - 2006// TI - Hypoxia inducible factor-1 activation by prolyl 4-hydroxylase-2 gene silencing attenuates myocardial ischemia reperfusion injury JO - Circ Res VL - 98 UR - https://doi.org/10.1161/01.RES.0000197816.63513.27 DO - 10.1161/01.RES.0000197816.63513.27 ID - Natarajan2006 ER - TY - JOUR AU - Rathmell, J. C. AU - Fox, C. J. AU - Plas, D. R. AU - Hammerman, P. S. AU - Cinalli, R. M. AU - Thompson, C. B. PY - 2003 DA - 2003// TI - Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival JO - Mol Cell Biol VL - 23 UR - https://doi.org/10.1128/MCB.23.20.7315-7328.2003 DO - 10.1128/MCB.23.20.7315-7328.2003 ID - Rathmell2003 ER - TY - JOUR AU - Lum, J. J. AU - Bui, T. AU - Gruber, T. AU - Gordan, J. D. AU - Deberardinis, R. J. AU - Covello, K. L. AU - Simon, M. C. AU - Thompson, C. B. PY - 2007 DA - 2007// TI - The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis JO - Genes Dev VL - 21 UR - https://doi.org/10.1101/gad.1529107 DO - 10.1101/gad.1529107 ID - Lum2007 ER - TY - JOUR AU - Morisette, M. R. AU - Howes, A. L. AU - Zhang, T. AU - Heller Brown, J. PY - 2003 DA - 2003// TI - Upregulation of GLUT1 expression is necessary for hypertrophy and survival of neonatal rat cardiomyocytes JO - J Mol Cell Cardiol VL - 35 UR - https://doi.org/10.1016/S0022-2828(03)00212-8 DO - 10.1016/S0022-2828(03)00212-8 ID - Morisette2003 ER - TY - JOUR AU - Stein, A. B. AU - Tang, X. L. AU - Guo, Y. AU - Xuan, Y. T. AU - Dawn, B. AU - Bolli, R. PY - 2004 DA - 2004// TI - Delayed adaptation of heart to stress: late preconditioning JO - Stroke VL - 35 UR - https://doi.org/10.1161/01.STR.0000143220.21382.fd DO - 10.1161/01.STR.0000143220.21382.fd ID - Stein2004 ER - TY - JOUR AU - Vanden Hoek, T. L. AU - Shao, Z. AU - Li, C. AU - Zak, R. AU - Schumacker, P. T. AU - Becker, L. B. PY - 1996 DA - 1996// TI - Reperfusion injury on cardiac myocytes after simulated ischemia JO - Am J Physiol VL - 270 ID - Vanden Hoek1996 ER - TY - JOUR AU - Thuerauf, D. J. AU - Marcinko, M. AU - Gude, N. AU - Rubio, M. AU - Sussman, M. A. AU - Glembotski, C. C. PY - 2006 DA - 2006// TI - Activation of the Unfolded Protein Response in Infracted Mouse Heart and Hypoxic cultured Cardiac Myocytes JO - Cir Res VL - 99 UR - https://doi.org/10.1161/01.RES.0000233317.70421.03 DO - 10.1161/01.RES.0000233317.70421.03 ID - Thuerauf2006 ER - TY - JOUR AU - Rutkowski, D. T. AU - Kaufman, R. J. PY - 2004 DA - 2004// TI - A trip to the ER: coping with stress JO - Trends Cell Biol VL - 14 UR - https://doi.org/10.1016/j.tcb.2003.11.001 DO - 10.1016/j.tcb.2003.11.001 ID - Rutkowski2004 ER - TY - JOUR AU - Harding, H. P. AU - Calfon, M. AU - Urano, F. AU - Novoa, I. AU - Ron, D. PY - 2002 DA - 2002// TI - Transcriptional and translational control in the mammalian unfolded protein response JO - Ann Rev Cell Biol VL - 18 UR - https://doi.org/10.1146/annurev.cellbio.18.011402.160624 DO - 10.1146/annurev.cellbio.18.011402.160624 ID - Harding2002 ER - TY - JOUR AU - Ozawa, T. AU - Hu, J. L. AU - Hu, L. J. AU - Kong, E. L. AU - Bollen, A. W. AU - Lamborn, K. R. AU - Deen, D. F. PY - 2005 DA - 2005// TI - Functionality of hypoxia-induced BAX expression in a human glioblastoma xenograft model JO - Cancer Gene Therapy VL - 12 ID - Ozawa2005 ER - TY - JOUR AU - Tanaka, T. AU - Hanafusa, N. AU - Ingelfinger, J. R. AU - Ohse, T. AU - Fujita, T. AU - Nangaku, M. PY - 2003 DA - 2003// TI - Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIF1-mediated upregulation of Bax JO - Biochem Biophys Res Commun VL - 309 UR - https://doi.org/10.1016/S0006-291X(03)01557-2 DO - 10.1016/S0006-291X(03)01557-2 ID - Tanaka2003 ER - TY - JOUR AU - Chen, D. AU - Li, M. AU - Luo, J. AU - Gu, W. PY - 2003 DA - 2003// TI - Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function JO - J Biol Chem VL - 278 UR - https://doi.org/10.1074/jbc.C200694200 DO - 10.1074/jbc.C200694200 ID - Chen2003 ER - TY - JOUR AU - Ding, W. X. AU - Ni, H. M. AU - Chen, X. AU - Yu, J. AU - Zhang, L. AU - Yin, X. M. PY - 2007 DA - 2007// TI - A coordinated action of Bax, PUMA, and p53 promotes MG-132-induced mitochondria activation and apoptosis in colon cancer cells JO - Mol Cancer Ther VL - 6 UR - https://doi.org/10.1158/1535-7163.MCT-06-0541 DO - 10.1158/1535-7163.MCT-06-0541 ID - Ding2007 ER - TY - JOUR AU - Cheng, J. AU - Cui, R. AU - Chen, C. H. AU - Du, J. PY - 2007 DA - 2007// TI - Oxidized Low-density lipoprotein stimulates p53-dependent activation of proapoptotic Bax leading to apoptosis of differentiated endothelial progenitor cells JO - Endocrinology VL - 148 UR - https://doi.org/10.1210/en.2006-1709 DO - 10.1210/en.2006-1709 ID - Cheng2007 ER - TY - JOUR AU - Mansfield, K. D. AU - Guzy, R. D. AU - Pan, Y. AU - Young, R. M. AU - Cash, T. P. AU - Schumaker, P. T. AU - Simon, M. C. PY - 2005 DA - 2005// TI - Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-1α activation JO - Cel Metab VL - 1 UR - https://doi.org/10.1016/j.cmet.2005.05.003 DO - 10.1016/j.cmet.2005.05.003 ID - Mansfield2005 ER - TY - JOUR AU - Chandel, N. S. AU - McClintock, D. S. AU - Feliciano, C. E. AU - Wood, T. M. AU - Melendez, J. A. AU - Rodriguez, A. M. AU - Schumaker, P. T. PY - 2000 DA - 2000// TI - Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor -1α during hypoxia: a mechanism of O2sensing JO - J Biol Chem VL - 275 UR - https://doi.org/10.1074/jbc.M001914200 DO - 10.1074/jbc.M001914200 ID - Chandel2000 ER - TY - JOUR AU - Zhang, L. AU - Li, L. AU - Liu, H. AU - Prabhakaran, K. AU - Zhang, X. AU - Borowitz, J. L. AU - Isom, G. E. PY - 2007 DA - 2007// TI - HIF-1 alpha activation by a redox-senstive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial dependent cell death JO - Free Radic Biol Med VL - 43 UR - https://doi.org/10.1016/j.freeradbiomed.2007.04.005 DO - 10.1016/j.freeradbiomed.2007.04.005 ID - Zhang2007 ER - TY - STD TI - The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/8/9/prepub UR - http://www.biomedcentral.com/1471-2261/8/9/prepub ID - ref51 ER -