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Prologue

  • Patrick L. Iversen
Chapter

Abstract

All living things are associated with a boundary defined ecological niche. Steady state conditions are rarely constant but evolutionary adaptation is too slow to adapt to daily threats so a surrogate variation mechanism is necessary. The genome defines the most basic instructions for life so that a molecular biology perspective provides the foundation for understanding resilience. Variations in the expression of RNA offers rapid variation and this book proposes this is the basis of resilience. This book attempts to illuminate mechanisms of resilience beginning with elaborating threats leading to disruption in steady state conditions. Recognition of threats and defense systems are described followed by adaptive changes in gene expression that refine responses. Finally, environmental conditions are discussed that serve to dampen the adaptive response oscillator to disruptive threats at the level of RNA expression.

This prologue is intended to acquaint the reader with my background and the genesis of optimism for an idea that the benefit of transcriptome plasticity is resilience. I grew up in several National Parks, remote regions of the United States that are set aside to preserve natural environments. I attended 12 schools by the time I graduated from high school, a fact that forced me to develop personal resilience. My career path as a scientist followed a path from ecologist to pharmacologist to molecular biologist. I was a professor that transitioned to biotechnology ensuring research subjects involving very diverse in subject matter so I appreciate the value of plasticity.

Keywords

Pharmacology Drug metabolism Chemical carcinogenesis Molecular biology Cytochrome P450 Exon skipping Resilience 

References

  1. Annalora AJ, Marcus CB, Iversen PL. Alternative splicing in the cytochrome P 450 superfamily expands protein Diverstiy to Augmewnt gene function and redirect human drug metabolism. Drug Metab Dispos. 2017;45:375–89.CrossRefGoogle Scholar
  2. Arora V, Knapp DC, Smith BL, Statdfield ML, Stein DA, Reddy MT, Weller DD, Iversen PL. C-Myc antisense limits rat liver regeneration and indicates role for c-myc in regulating cytochrome P-450 3A activity. J Pharmacol Exp Ther. 2000;292:921–8.PubMedGoogle Scholar
  3. Bayever E, Haines K, Iversen PL, Ruddon RW, Pirruccello SJ, Mountjoy CP, Arneson MA, Smith LJ. Selective cytotoxicity of human leukemic Myeloblasts produced by Oligodeoxyribonucleic Phosphorothioate complementary to p 53 nucleotide sequences. Leuk Lymphoma. 1993a;12:223–31.CrossRefGoogle Scholar
  4. Bayever E, Iversen PL, Bishop M, Sharp JG, Tewary HK, Arneson MA, Pirruccello SJ, Ruddon RW, Kessinger A, Zon G, Armitage JO. Systemic administration of a Phosphorothioate oligonucleotide with a sequence complementary to p 53 for acute myelogenous leukemia and myelodysplastic syndrome: initial results of a phase I trial. Antisense Res Dev. 1993b;3:383–90.CrossRefGoogle Scholar
  5. Copple BL, Gmeiner WM, Iversen PL. Reaction between metabolically activated acetaminophen and Phosphorothioate oligonucleotides. Toxicol Appl Pharmacol. 1995;133:53–63.CrossRefGoogle Scholar
  6. Cornish KG, Iversen PL, Smith LJ, Arneson MA, Bayever E. Cardiovascular effects of a phosphorothioate oligonucleotide with sequence antisense to p 53 in the conscious rhesus monkey. Pharmacol Commun. 1993;3:239–47.Google Scholar
  7. Deas TS, Binduga-Gajewska I, Tilgner M, Ren P, Stein DA, Moulton HM, Iversen PL, Kauffman EB, Kramer LD, Shi P-Y. Inhibition of Flavivirus infections by antisense oligomers specifically suppressing viral translation and RNA replication. J Virology. 2005;79(8):4599–609.CrossRefGoogle Scholar
  8. Desjardins JP, Iversen PL. Inhibition of the rat cytochrome P 450 3A2 by an antisense Phosphorothiaote Oligodeoxynucleotide in vivo. J Pharm Exptl Ther. 1995;275(3):1608–13.Google Scholar
  9. Desjardins J, Mata J, Brown T, Zon G, Iversen PL. Cholesteryl-conjugated phosphorothioate oligonucleotides modulate CYP2B1 expression in vivo. J Drug Target. 1995;2:477–85.CrossRefGoogle Scholar
  10. Desjardins JP, Sproat BS, Beijer B, Blaschke M, Dunkel M, Gerdes W, Ludwig J, Reither V, Rupp T, Iversen PL. Pharmacokinetics of a synthetic chemically modified hammerhead ribozyme against the rat cytochrome P-450 3A2 mRNA after single intravenous injection. J Pharm Exptl Ther. 1996;278(3):1–9.Google Scholar
  11. Dogini DB, Pascoal VDAB, Avansiini SH, Viera AS, Pereira TC, Lopes-Cendes I. The new world of RNAs. Genet Mol Biol. 2014;37:285–93.CrossRefGoogle Scholar
  12. Egan W, Boal J, Iyer R, Strom C, Wilson S, Meyer A, Iversen P. Abasic oligodeoxyribonucleotide phosphorothioates as inhibitors of the human immunodeficiency virus-1 (HIV-1): phosphorothioate inhibition of HIV-1 reverse transcriptase and interactions with Syrian hamster fibroblast (V79) cells. Nucleosides Nucleotides. 1991;10(1–3):457–60.CrossRefGoogle Scholar
  13. Ge Q, Pastey M, Kobasa D, Puthavathana P, Lupfer C, Bestwick RK, Iversen PL, Chen J, Stein DA. Inhibition of multiple subtypes of influenza a virus in cell cultures with morpholino oligomers. Antimicrob Agents Chemother. 2006;50(11):3724–33.CrossRefGoogle Scholar
  14. Geller BL, Deere JD, Stein DA, Kroeker AD, Moulton HM, Iversen PL. Inhibition of gene expression in Escherichia coli by antisense Phosphorodiamidate Morpholino oligomers. Antimicrob Agents Chemother. 2003;47:3233–9.CrossRefGoogle Scholar
  15. Hanson GR, Partlow LM, Iversen PL. Neuronal stimulation of non-neuronal (glial) cell proliferation: lack of specificity between different regions of the nervous system. Dev Brain Res. 1982;3:547–55.CrossRefGoogle Scholar
  16. Heald AE, Iversen PL, Saoid JB, Sazani P, Charleston JS, Axtelle T, Wong M, Smith WB, Vutikullird A, Kaye E. Safety and pharmacokinetic profiles of Phosphorodiamidate Morpholino oligomers with activity against Ebola virus and Marburg virus: results of two single ascending dose studies. Antimicrob Agents Chemother. 2014;58(11):6639–47. 25155593CrossRefGoogle Scholar
  17. Heald AE, Charleston JS, Iversen PL, Warren T, Saoud JB, Al-Ibrahim M, Wells J, Warfield KL, Swenson DL, Welch L, Sazani P, Wong M, Berry D, Kaye E, Bavari S. AVI-7288 for Marburg virus in nonhuman Primates and humans. N Engl J Med. 2015;373(4):339–48. 26200980CrossRefGoogle Scholar
  18. Hines RN, Levy JB, Conrad RD, Iversen PL, Shen ML, Bresnick E. Gene structure and nucleotide sequence for rat cytochrome P-450c. Arch Biochem Biophys. 1985;237:467–76.CrossRefGoogle Scholar
  19. Hudziak RM, Summerton J, Weller DD, Iversen PL. Antiproliferative effects of steric blocking Phosphorodiamidate Morpholino antisense agents directed against c-myc. Antisense Nucleic Acid Drug Dev. 2000;10:163–76.CrossRefGoogle Scholar
  20. Iversen PL. In vivo studies with Phosphorothioate oligonucleotides: pharmacokinetic Prolgue. Anticancer Drug Des. 1991;6:531–8.PubMedGoogle Scholar
  21. Iversen PL, Partlow LM, Stensaas LJ, Motamed F. Characterization of a variety of standard collagen substrates: ultrastructure, uniformity, and the capacity to bind and promote growth of neurons. In Vitro. 1981;17(5):540–52.CrossRefGoogle Scholar
  22. Iversen PL, Liu Z, Franklin MR. Selective changes in cytochrome P-450 and UDP-glucuronosyl transferase subpopulations following partial hepatectomy in rats. Toxicol Appl Pharmacol. 1985;78:10–8.CrossRefGoogle Scholar
  23. Iversen PL, Heiger WJ, Bresnick E, Hines RN. Structural details of the human cytochrome P-450c gene. Arch Biochem Biophys. 1987;256:397.CrossRefGoogle Scholar
  24. Iversen PL, Mata JE, Tracewell WG, Zon G. Pharmacokinetics of an antisense Phosphorothioate Oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in the adult male rat following single injections and continuous infusion. Antisense Res Dev. 1994;4:43–52.CrossRefGoogle Scholar
  25. Iversen PL, Warren TK, Wells JB, Garza NL, Mourich DV, Welch LS, Panchal RG, Ad Bavari S. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections. Viruses. 2012;4(11):280–2830. 23202506CrossRefGoogle Scholar
  26. Kessell SR. Wildland inventories and fire modeling by gradient analysis in glacier National Park. In: Gradient modeling: resource and fire Management: Springer; 1976. p. 115–62.Google Scholar
  27. Kinney RM, Huang CL-H, Rose BC, Kroeker AD, Dreher TW, Iversen PL, Stein DA. Inhibition of dengue virus serotypes 1 to 4 in cell culture with Morpholino oligomers. J Virology. 2005;79(8):5116–28.CrossRefGoogle Scholar
  28. Kipshidze NN, Kim H-S, Iversen PL, Yazdi HA, Bhargava B, Mehran R, Haundenschild C, Dangas G, Stone GW, Roubin GS, Leon MB, Moses JW. Intramural delivery of advanced antisense oligonucleotides with infiltrator Cathetor inhibits c-myc expression and intimal hyperplasia in the porcine. J Am Col Cardiology. 2002;39(10):1686–91.CrossRefGoogle Scholar
  29. Kipshidze N, Iversen P, Overlie P, Dunlap T, Titus B, Lee D, Moses J, O’Hanley P, Lauer M, Leon MB. First human experience with local delivery of novel antisense AVI-4126 with infiltrator catheter in de novo native and restenotic coronary arteries: 6-month clinical and angiographic follow-up from AVAIL study. Cardiovas Revasc Med. 2007;8(4):230–5.CrossRefGoogle Scholar
  30. Kornfeld JW, Bruning JC. Regulation of metabolism by long, non-coding RNAs. Front Genet. 2014;5:1–8.CrossRefGoogle Scholar
  31. Lai SH, Stein DA, Liao SL, Guerrero-Plata A, Hong C, Iversen PL, Casola A, Garofalo RP. Inhibition of respiratory Syncitial virus infections in cell cultures and in mice with Morpholino oligomers. Mol Ther. 2008;16(6):1120–8.CrossRefGoogle Scholar
  32. Neuman BW, Stein DA, Kroeker AD, Paulino AD, Moulton HM, Iversen PL, Buchmeier MJ. Antisense Morpholino oligomers directed against the 5′-end of the genome inhibit coronavirus proliferation and growth. J Virol. 2004;78(11):5891–9.CrossRefGoogle Scholar
  33. Neuman BW, Stein DA, Kroeker AD, Churchill MJ, Kim AM, Dawson P, Moulton HM, Bestwick RK, Iversen PL, Buchmeier MJ. Inhibition, escape and attenuation of SARS coronavirus treated with antisense morpholino oligomers. J Virology. 2005;79:9665–76.CrossRefGoogle Scholar
  34. Paessler S, Rijnbrand R, Stein DA, Ni H, Yun NE, Dziuba N, Borisevich V, Seregin A, Ma Y, Blouch R, Iversen PL, Zacks MA. Inhibition of alphavirus infection in cell culture and in mice with antisense morpholino oliogmers. Virology. 2008;5(2):357–70.CrossRefGoogle Scholar
  35. Schlegel RA, Iversen PL, Rechsteiner MC. The turnover of tRNAs microinjected into animal cells. Nucleic Acids Res. 1978;5(10):3715–29.CrossRefGoogle Scholar
  36. Skorski T, Nieborowska-Skorska M, Nicolaides NC, Szczylik C, Iversen P, Isso RV, Zon G, Calabretta B. Suppression of Philadelphia leukemia cell growth in mice by bcr-abl antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1994;91:4504–8.CrossRefGoogle Scholar
  37. St. Laurent G, Vyatkiin Y, Kapranov P. Dark matter RNA illuminates the puzzle of genome-wide association studies. BMC Med. 2014;12:97–105.CrossRefGoogle Scholar
  38. Stein DA, Skilling DE, Iversen PL, Smith AW. Inhibition of Vesivirus Infetions in mammalian tissue culture with antisense Morpholino oligomers. Antisense Nucleic Acid Drug Dev. 2001;11:317–25.CrossRefGoogle Scholar
  39. Stevenson M, Iversen PL. Inhibition of HIV mediated Cytopathicityby poly-L-lysine conjugated synthetic antisense Oligodeoxyribonucleotides. J Gen Virol. 1989;70:2673–82.CrossRefGoogle Scholar
  40. Stone J, Stein DA, Rijnbrand R, Iversen PL, Andino R. Inhibition of multiple species of picornavirus using a morpholino oligomer targeting highly conserved IRES sequence. Antimicrob Agents Chemother. 2008;52(6):1970–81.CrossRefGoogle Scholar
  41. Warren TK, Warfield KL, Wells J, Swenson DL, Donner KS, Van Tongeren SA, Garza NL, Dong L, Mourich DV, Crumley S, Nichols DK, Iversen PL, Bavari S. Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat Med. 2010;16:991–4.CrossRefGoogle Scholar
  42. Worley C. et al. Ecological planning for a safe environment: studies of man’s impact on the Utah Strawberry reservoir. Westminster College, Salt Lake City, Utah June 1, 1976-August 31, 1976. 1977.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Patrick L. Iversen
    • 1
  1. 1.LS PharmaOregon State UniversityGrand JctUSA

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