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Regulation of target gene expression by the vitamin D receptor - an update on mechanisms

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Abstract

Virtually all of the known biological actions of the hormonal ligand 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR). Following binding and activation by the ligand, the VDR localizes in the nucleus to the regulatory regions of target genes and recruits chromatin-active coregulatory complexes which, in turn, modulate transcriptional output. The failure of the VDR to function due to crippling mutations results in total hereditary resistance to 1,25(OH)2D3 in both mice and humans. In this review, we summarize the structural and functional properties of the VDR and the role of 1,25(OH)2D3 in receptor activation, and then describe the results of recent studies using genome-wide analyses that define the overarching principles through which the VDR modulates genes expression. We also focus on the recent analysis of a specific 1,25(OH)2D3 regulated gene that provides confirmation of the principles identified through these genome-wide methodologies. Taken together, these studies suggest an unanticipated increase in the complexity of the molecular processes that govern gene regulation by hormones and other factors.

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References

  1. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80:1689S–96.

    PubMed  CAS  Google Scholar 

  2. Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010;9:941–55.

    Article  PubMed  CAS  Google Scholar 

  3. Pike JW, Meyer MB, Martowicz ML, Bishop KA, Lee SM, Nerenz RD, et al. Emerging regulatory paradigms for control of gene expression by 1,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 2010;121:130–5.

    Article  PubMed  CAS  Google Scholar 

  4. Hoenderop JGJ, Nilius B, Bindels RJM. Calcium absorption across epithelia. Physiol Rev. 2005;85:373–422.

    Article  PubMed  CAS  Google Scholar 

  5. Nijenhuis T, Hoenderop JG, Bindels RJ. TRPV5 and TRPV6 in Ca2+ (re)absorption: regulating Ca2+ entry at the gate. Pflugers Arch. 2005;451:181–92.

    Article  PubMed  CAS  Google Scholar 

  6. Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R, et al. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol. 2009;297:F282–91.

    Article  PubMed  CAS  Google Scholar 

  7. Segawa H, Onitsuka A, Furutani J, Kaneko I, Aranami F, Matsumoto N, et al. Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development. Am J Physiol Renal Physiol. 2009;297:F671–8.

    Article  PubMed  CAS  Google Scholar 

  8. Tomoe Y, Segawa H, Shiozawa K, Kaneko I, Tominaga R, Hanabusa E, et al. Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice. Am J Physiol Renal Physiol. 2010;298:F1341–50.

    Article  PubMed  CAS  Google Scholar 

  9. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–76.

    Article  PubMed  CAS  Google Scholar 

  10. Bucay N, Sarosi I, Dunstan C, Morony S, Tarpley J, Capparelli C, et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998;12:1260–8.

    Article  PubMed  CAS  Google Scholar 

  11. Bergwitz C, Banerjee S, Abu-Zahra H, Kaji H, Miyauchi A, Sugimoto T, et al. Defective O-glycosylation due to a novel homozygous S129P mutation is associated with lack of fibroblast growth factor 23 secretion and tumoral calcinosis. J Clin Endocrinol Metab. 2009;94:4267–74.

    Article  PubMed  CAS  Google Scholar 

  12. Bergwitz C, Jüppner H. Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med. 2010;61:91–104.

    Article  PubMed  CAS  Google Scholar 

  13. Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T, et al. Differentiation of mouse myeloid leukemia cells induced by 1a,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981;78:4990–4.

    Article  PubMed  CAS  Google Scholar 

  14. Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002;296:1313–6.

    Article  PubMed  CAS  Google Scholar 

  15. Schmiedlin-Ren P, Thummel KE, Fisher JM, Paine MF, Watkins PB. Induction of CYP3A4 by 1 alpha,25-dihydroxyvitamin D3 is human cell line-specific and is unlikely to involve pregnane X receptor. Drug Metab Dispos. 2001;29:1446–53.

    PubMed  CAS  Google Scholar 

  16. Thummel KE, Brimer C, Yasuda K, Thottassery J, Senn T, Lin Y, et al. Transcriptional control of intestinal cytochrome P-4503A by 1a,25-dihydroxy vitamin D3. Mol Pharmacol. 2001;60:1399–406.

    PubMed  CAS  Google Scholar 

  17. Hewison M. Vitamin D and innate and adaptive immunity. Vitam Horm. 2011;86:23–62.

    Article  PubMed  CAS  Google Scholar 

  18. Bikle DD. Vitamin D and the skin. J Bone Miner Metab. 2010;28:117–30.

    Article  PubMed  CAS  Google Scholar 

  19. Cianferotti L, Cox M, Skorija K, Demay MB. Vitamin D receptor is essential for normal keratinocyte stem cell function. Proc Natl Acad Sci U S A. 2007;104:9428–33.

    Article  PubMed  CAS  Google Scholar 

  20. Wu-Wong JR. The potential for vitamin D receptor activation in cardiovascular research. Exp Opin Invest Drugs. 2007;16:407–11.

    Article  CAS  Google Scholar 

  21. Wu-Wong JR. Potential for vitamin D receptor agonists in the treatment of cardiovascular disease. Br J Pharmacol. 2009;158:395–412.

    Article  PubMed  CAS  Google Scholar 

  22. Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, et al. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A. 1988;85:3294–8.

    Article  PubMed  CAS  Google Scholar 

  23. Burmester JK, Maeda N, DeLuca HF. Isolation and expression of rat 1,25-dihydroxyvitamin D3 receptor cDNA. Proc Natl Acad Sci U S A. 1988;85:1005–9.

    Article  PubMed  CAS  Google Scholar 

  24. Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988;240:889–95.

    Article  PubMed  CAS  Google Scholar 

  25. Haussler M, Whitfield G, Haussler C, Hsieh J, Thompson P, Selznick S, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res. 1998;13:325–49.

    Article  PubMed  CAS  Google Scholar 

  26. Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000;5:173–9.

    Article  PubMed  CAS  Google Scholar 

  27. Vanhooke JL, Benning MM, Bauer CB, Pike JW, DeLuca HF. Molecular structure of the rat vitamin D receptor ligand binding domain complexed with 2-carbon-substituted vitamin D3 hormone analogues and a LXXLL-containing coactivator peptide. Biochemistry. 2004;43:4101–10.

    Article  PubMed  CAS  Google Scholar 

  28. Pike J, Sleator N. Hormone-dependent phosphorylation of the 1,25-dihydroxyvitamin D3 receptor in mouse fibroblasts. Biochem Biophys Res Commun. 1985;131:378–85.

    Article  PubMed  CAS  Google Scholar 

  29. Hsieh JC, Jurutka PW, Nakajima S, Galligan MA, Haussler CA, Shimizu Y, et al. Phosphorylation of the human vitamin D receptor by protein kinase C. Biochemical and functional evaluation of the serine 51 recognition site. J Biol Chem. 1993;268:15118–26.

    PubMed  CAS  Google Scholar 

  30. Kerner SA, Scott RA, Pike JW. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3. Proc Natl Acad Sci U S A. 1989;86:4455–9.

    Article  PubMed  CAS  Google Scholar 

  31. Ozono K, Liao J, Kerner SA, Scott RA, Pike JW. The vitamin D-responsive element in the human osteocalcin gene. Association with a nuclear proto-oncogene enhancer. J Biol Chem. 1990;265:21881–8.

    PubMed  CAS  Google Scholar 

  32. Carlberg C. Molecular basis of the selective activity of vitamin D analogues. J Cell Biochem. 2003;88:274–81.

    Article  PubMed  CAS  Google Scholar 

  33. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995;83:841–50.

    Article  PubMed  CAS  Google Scholar 

  34. Demay MB, Kiernan MS, DeLuca HF, Kronenberg HM. Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1992;89:8097–101.

    Article  PubMed  CAS  Google Scholar 

  35. Kim MS, Fujiki R, Murayama A, Kitagawa H, Yamaoka K, Yamamoto Y, et al. 1Alpha,25(OH)2D3-induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter. Mol Endocrinol. 2007;21:334–42.

    Article  PubMed  CAS  Google Scholar 

  36. Murayama A, Kim MS, Yanagisawa J, Takeyama K, Kato S. Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. EMBO J. 2004;23:1598–608.

    Article  PubMed  CAS  Google Scholar 

  37. Kim MS, Fujiki R, Kitagawa H, Kato S. 1alpha,25(OH)2D3-induced DNA methylation suppresses the human CYP27B1 gene. Mol Cell Endocrinol. 2007;265–266:168–73.

    Article  PubMed  Google Scholar 

  38. McKenna N, O'Malley B. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell. 2002;108:465–74.

    Article  PubMed  CAS  Google Scholar 

  39. Ren B. Transcription: Enhancers make non-coding RNA. Nature. 2010;465:173–4.

    Article  PubMed  CAS  Google Scholar 

  40. Hawkins RD, Hon GC, Ren B. Next-generation genomics: an integrative approach. In: Nat Rev Genet. 2010;476–486

  41. Pike JW. Genome-scale techniques highlight the epigenome and redefine fundamental principles of gene regulation. J Bone Miner Res. 2011;26:1155–62.

    Article  PubMed  CAS  Google Scholar 

  42. Jurutka PW, Bartik L, Whitfield GK, Mathern DR, Barthel TK, Gurevich M, et al. Vitamin D receptor: key roles in bone mineral pathophysiology, molecular mechanism of action, and novel nutritional ligands. J Bone Miner Res. 2007;22 Suppl 2:V2–10.

    Article  PubMed  CAS  Google Scholar 

  43. Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, et al. Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem. 2010;21:1153–61.

    Article  PubMed  CAS  Google Scholar 

  44. Nehring J, Zierold C, DeLuca H. Lithocholic acid can carry out in vivo functions of vitamin D. Proc Natl Acad Sci U S A. 2007;104:10006–9.

    Article  PubMed  CAS  Google Scholar 

  45. Schmidt DR, Holmstrom SR, Fon Tacer K, Bookout AL, Kliewer SA, Mangelsdorf DJ. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J Biol Chem. 2010;285:14486–94.

    Article  PubMed  CAS  Google Scholar 

  46. Marx SJ, Spiegel AM, Brown EM, Gardner DG, Downs RW, Attie M, et al. A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab. 1978;47:1303–10.

    Article  PubMed  CAS  Google Scholar 

  47. Malloy P, Xu R, Cattani A, Reyes L, Feldman D. A unique insertion/substitution in helix H1 of the vitamin D receptor ligand binding domain in a patient with hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Bone Miner Res. 2004;19:1018–24.

    Article  PubMed  CAS  Google Scholar 

  48. Balsan S, Garabédian M, Larchet M, Gorski AM, Cournot G, Tau C, et al. Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D. J Clin Invest. 1986;77:1661–7.

    Article  PubMed  CAS  Google Scholar 

  49. Eil C, Liberman UA, Rosen JF, Marx SJ. A cellular defect in hereditary vitamin-D-dependent rickets type II: defective nuclear uptake of 1,25-dihydroxyvitamin D in cultured skin fibroblasts. N Engl J Med. 1981;304:1588–91.

    Article  PubMed  CAS  Google Scholar 

  50. Sone T, Scott R, Hughes M, Malloy P, Feldman D, O'Malley B, et al. Mutant vitamin D receptors which confer hereditary resistance to 1,25-dihydroxyvitamin D3 in humans are transcriptionally inactive in vitro. J Biol Chem. 1989;264:20230–4.

    PubMed  CAS  Google Scholar 

  51. Forghani N, Lum C, Krishnan S, Wang J, Wilson D, Blackett P, et al. Two new unrelated cases of hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia resulting from the same novel nonsense mutation in the vitamin D receptor gene. J Pediatr Endocrinol Metab. 2010;23:843–50.

    Article  PubMed  CAS  Google Scholar 

  52. Skorija K, Cox M, Sisk JM, Dowd DR, MacDonald PN, Thompson CC, et al. Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. Mol Endocrinol. 2005;19:855–62.

    Article  PubMed  CAS  Google Scholar 

  53. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.

    Article  PubMed  CAS  Google Scholar 

  54. Kirmizis A, Farnham PJ. Genomic approaches that aid in the identification of transcription factor target genes. Exp Biol Med (Maywood). 2004;229:705–21.

    CAS  Google Scholar 

  55. Valouev A, Johnson D, Sundquist A, Medina C, Anton E, Batzoglou S, et al. Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data. Nat Methods. 2008;5:829–34.

    Article  PubMed  CAS  Google Scholar 

  56. McDowell JC, Park M, Thomas PJ, Young AC, Blakesley RW, Muzny DM, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447:799–816.

    Article  PubMed  Google Scholar 

  57. Meyer MB, Goetsch PD, Pike JW. Genome-wide analysis of the VDR/RXR cistrome in osteoblast cells provides new mechanistic insight into the actions of the vitamin D hormone. J Steroid Biochem Mol Biol. 2010;121:136–41.

    Article  PubMed  CAS  Google Scholar 

  58. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010;20:1352–60.

    Article  PubMed  CAS  Google Scholar 

  59. Kim S, Yamazaki M, Zella LA, Shevde NK, Pike JW. Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. Mol Cell Biol. 2006;26:6469–86.

    Article  PubMed  CAS  Google Scholar 

  60. Zella LA, Kim S, Shevde NK, Pike JW. Enhancers located within two introns of the vitamin D receptor gene mediate transcriptional autoregulation by 1,25-dihydroxyvitamin D3. Mol Endocrinol. 2006;20:1231–47.

    Article  PubMed  CAS  Google Scholar 

  61. Meyer MB, Goetsch PD, Pike JW. A downstream intergenic cluster of regulatory enhancers contributes to the induction of CYP24A1 Expression by 1alpha,25-dihydroxyvitamin D3. J Biol Chem. 2010;285:15599–610.

    Article  PubMed  CAS  Google Scholar 

  62. Jin CH, Pike JW. Human vitamin D receptor-dependent transactivation in Saccharomyces cerevisiae requires retinoid X receptor. Mol Endocrinol. 1996;10:196–205.

    Article  PubMed  CAS  Google Scholar 

  63. Carroll JS, Liu XS, Brodsky AS, Li W, Meyer CA, Szary AJ, et al. Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell. 2005;122:33–43.

    Article  PubMed  CAS  Google Scholar 

  64. Carroll J, Meyer C, Song J, Li W, Geistlinger T, Eeckhoute J, et al. Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006;38:1289–97.

    Article  PubMed  CAS  Google Scholar 

  65. Zella L, Meyer M, Nerenz R, Lee S, Martowicz M, Pike J. Multifunctional enhancers regulate mouse and human vitamin D receptor gene transcription. Mol Endocrinol. 2010;24:128–47.

    Article  PubMed  CAS  Google Scholar 

  66. Martowicz ML, Meyer MB, Pike JW. The mouse RANKL gene locus is defined by a broad pattern of histone H4 acetylation and regulated through distinct distal enhancers. J. Cell. Biochem. 2011;112:2030–45.

    Google Scholar 

  67. Ong CT, Corces VG. Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet. 2011;12:283–93.

    Article  PubMed  CAS  Google Scholar 

  68. Pike J, Zella L, Meyer M, Fretz J, Kim S. Molecular actions of 1,25-dihydroxyvitamin D3 on genes involved in calcium homeostasis. J Bone Miner Res. 2007;22 Suppl 2:V16–9.

    Article  PubMed  CAS  Google Scholar 

  69. Yasuda H, Higashio K, Suda T. Vitamin D and osteoclastogenesis. In: Feldman D, Pike JW, Glorieux FH, editors. Vitamin D. 2nd ed. New York: Elsevier/Academic Press; 2005. p. 665–85.

    Chapter  Google Scholar 

  70. Leibbrandt A, Penninger JM. RANK/RANKL: regulators of immune responses and bone physiology. Ann N Y Acad Sci. 2008;1143:123–50.

    Article  PubMed  CAS  Google Scholar 

  71. Kitazawa S, Kajimoto K, Kondo T, Kitazawa R. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter. J Cell Biochem. 2003;89:771–7.

    Article  PubMed  CAS  Google Scholar 

  72. Fan X, Roy E, Murphy T, Nanes M, Kim S, Pike J, et al. Regulation of RANKL promoter activity is associated with histone remodeling in murine bone stromal cells. J Cell Biochem. 2004;93:807–18.

    Article  PubMed  CAS  Google Scholar 

  73. Nerenz RD, Martowicz ML, Pike JW. An enhancer 20 kilobases upstream of the human receptor activator of nuclear factor-kappaB ligand gene mediates dominant activation by 1,25-dihydroxyvitamin D3. Mol Endocrinol. 2008;22:1044–56.

    Article  PubMed  CAS  Google Scholar 

  74. Fu Q, Manolagas SC, O'Brien CA. Parathyroid hormone controls receptor activator of NF-kappaB ligand gene expression via a distant transcriptional enhancer. Mol Cell Biol. 2006;26:6453–68.

    Article  PubMed  CAS  Google Scholar 

  75. Kim S, Yamazaki M, Shevde NK, Pike JW. Transcriptional control of receptor activator of nuclear factor-kappaB ligand by the protein kinase A activator forskolin and the transmembrane glycoprotein 130-activating cytokine, oncostatin M, is exerted through multiple distal enhancers. Mol Endocrinol. 2007;21:197–214.

    Article  PubMed  CAS  Google Scholar 

  76. Bishop KA, Meyer MB, Pike JW. A novel distal enhancer mediates cytokine induction of mouse RANKl gene expression. Mol Endocrinol. 2009;23:2095–110.

    Article  PubMed  CAS  Google Scholar 

  77. Bishop KA, Coy HM, Nerenz RD, Meyer MB, Pike JW. Mouse Rankl expression is regulated in T cells by c-Fos through a cluster of distal regulatory enhancers designated the T cell control region. J. Biol. Chem. 2011;286:20880–91.

    Google Scholar 

  78. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science. 2002;295:1306–11.

    Article  PubMed  CAS  Google Scholar 

  79. Tasic B, Hippenmeyer S, Wang C, Gamboa M, Zong H, Chen-Tsai Y, et al. Site-specific integrase-mediated transgenesis in mice via pronuclear injection. Proc Natl Acad Sci U S A. 2011;108:7902–7.

    Article  PubMed  CAS  Google Scholar 

  80. Galli C, Zella LA, Fretz JA, Fu Q, Pike JW, Weinstein RS, et al. Targeted deletion of a distant transcriptional enhancer of the receptor activator of nuclear factor-kappaB ligand gene reduces bone remodeling and increases bone mass. Endocrinology. 2008;149:146–53.

    Article  PubMed  CAS  Google Scholar 

  81. Lin YC, Jhunjhunwala S, Benner C, Heinz S, Welinder E, Mansson R, et al. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat Immunol. 2010;11:635–43.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge the contributions of each of the members of the Pike laboratory toward the work discussed and the artistic skills of Laura Vanderploeg in the figures presented. This work was supported by National Institute of Heath Grants DK-072281, DK-073995, DK-074993 and AR-045173.

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  1. Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, 53706, USA

    J. Wesley Pike, Mark B. Meyer & Kathleen A. Bishop

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  1. J. Wesley Pike
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Correspondence to J. Wesley Pike.

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Pike, J.W., Meyer, M.B. & Bishop, K.A. Regulation of target gene expression by the vitamin D receptor - an update on mechanisms. Rev Endocr Metab Disord 13, 45–55 (2012). https://doi.org/10.1007/s11154-011-9198-9

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