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Bad News with a side of Good news

Bad News with a side of Good news. Genetic Syndromes Teratogens Endocrine disruption Cancer Anti-angiogenesis treatment Induced Pluripotent Stem Cells Regenerative Biology. A New Hope. Phantom Menace. Attack of the Clones. Lucky to be here!. 17.1. Better to be lucky than good?.

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Bad News with a side of Good news

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  1. Bad News with a side of Good news • Genetic Syndromes • Teratogens • Endocrine disruption • Cancer • Anti-angiogenesis treatment • Induced Pluripotent Stem Cells • Regenerative Biology A New Hope Phantom Menace Attack of the Clones

  2. Lucky to be here! 17.1

  3. Better to be lucky than good? occasionally live a short time

  4. Nondisjunction Fig 16.4

  5. Human Syndromes • Mosaic pleiotropy • Relational pleiotropy • Genetic and Phenotypic heterogeneity.

  6. Teratogenesis • DDT- pesticide • Thalidomide- sedative during pregnancies • Rubella- 1964 epidemic leading to 20,000 blind, deaf, or both fetuses. DDT Thalidomide

  7. Timing is everything Fig. 17.5

  8. Teratogens • Table 17.2

  9. Alcohol • Fetal Alcohol Syndrome (FAS) • 1 out of 650 children • Fetal alcohol Spectrum Disorder (FASD) • 3 times as many kids with FASD than FAS

  10. Retinoic Acid • Accutane: 13-cis-retinoic acid • Hox gene expression • Pharyngeal Arches

  11. Endocrine disruptors • Hormonal Agonists/Antagonists • Block Synthesis, elimination and transportation of hormones • Prime organism to be more sensitive to hormones PCBs Bisphenol A (BPA) Diethylstibestrol (DES)

  12. Diethylstibestrol (DES) • Gonad Development • Hoxa10 regulation • Guess who? BMP or Wnt? 17.9 then 17.11, then 17.12

  13. Plastic bottles a source of teratogens? • Nonylphenol • Bisphenol A Fig. 16.22 and 16.25

  14. Nonylphenol • Tufts University- estrogen responsive tumor cells • Plastic containers that held water and serum were culprit.

  15. Bisphenol A (BPA) • Developed as a synthetic estrogen • 2 Billion Pounds still produced yearly • Used for: • Resin lining in most cans • Polycarbonate plastic in baby bottles, childrens toys • Dental sealant. • Brightly colored polycarbonate bottles • Water in Polycarbonate bottles for week at Room Temp. • 300 mg per liter of BPA

  16. Bisphenol A (BPA) Figure 17.13 and 17.14 • Low dose exposure • Meiotic defects • Predispostion to breast cancer • 95% of individuals tested in U.S. and Japan have measurable amounts of BPA in urine • Plastics industry claims “evidence is meager” • Nalgene and Wal-Mart no longer make or sell BPA containing bottles.

  17. Other teratogens • Heavy Metals • Pathogens • Rubella- within first 6 weeks • Toxoplasmagondii

  18. Cancer: a disease of development • Context dependent tumors • Cell-cell communication • Paracrine pathways • Cancer Stem cell hypothesis • MITF and melanocytes • Embryonic migration pathways • Epigenetic reprogramming

  19. Cancer Stem Cell Hypothesis

  20. Cancer: a disease of development • Context dependent tumors • Cell-cell communication • Paracrine pathways • Cancer Stem cell hypothesis • MITF and melanocytes • Embryonic migration pathways • Epigenetic reprogramming

  21. Cancer: Epigenetic reprogramming

  22. Cancer: Epigenetic reprogramming

  23. Light at end of tunnel.. • Anti-Angiogenesis • Stem cells and tissue regeneration

  24. Anti-Angiogenesis • VEGFs • Fgfs 17.22

  25. Embryonic Stem Cells • Embryonic stem cells • Embryonic germ cells 17.23

  26. Induced Pluripotent stem cells • Fbx15 enhancer • OCT4, SOX2, c-MYC, and KLF4 17.25

  27. Induced Pluripotent stem cells • Use of viral vectors • Inject fibroblasts transduced with OCT4, SOX2, KLF4, and c-MYC. 17.26

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