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  <head>
    <title>082-03 Cell-cycle control, division, stem cells, senescence, and experimental observation</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Cell cycle, stem cells, senescence, and methods">
      <outline text="Cycle phases and fates">
        <outline text="Gap one, synthesis, gap two, mitosis"/>
        <outline text="G zero quiescence is reversible"/>
        <outline text="Other exits: differentiation, senescence, death"/>
        <outline text="Tissues balance outcomes by signals and context"/>
      </outline>
      <outline text="Cyclin-dependent kinase control">
        <outline text="Stage-specific cyclins activate kinases">
          <outline text="Cyclin D with four or six: mitogens"/>
          <outline text="Cyclin E with two: synthesis entry"/>
          <outline text="Cyclin B with one: mitosis"/>
        </outline>
        <outline text="Ubiquitin destruction makes transitions one-way"/>
        <outline text="Restriction point commits to division">
          <outline text="Phosphorylated retinoblastoma protein frees E two F"/>
          <outline text="Loss of control drives proliferation"/>
        </outline>
        <outline text="Growth signals and nutrients gate division">
          <outline text="Rapamycin target integrates nutrients and energy"/>
          <outline text="AMP-activated kinase suppresses anabolism"/>
        </outline>
      </outline>
      <outline text="Replication and checkpoints">
        <outline text="Origins licensed before synthesis">
          <outline text="Activation blocks relicensing"/>
        </outline>
        <outline text="Replication stress from stalled forks"/>
        <outline text="Ataxia telangiectasia mutated kinase">
          <outline text="Responds to double-strand breaks"/>
        </outline>
        <outline text="Related kinase: replication stress"/>
        <outline text="p fifty-three: p twenty-one arrest or apoptosis"/>
        <outline text="Gap two switch into mitosis">
          <outline text="Phosphatases remove inhibitory phosphate"/>
          <outline text="Positive feedback prevents mixed states"/>
        </outline>
      </outline>
      <outline text="Mitosis and cytokinesis">
        <outline text="Cohesin holds sister chromatids"/>
        <outline text="Kinetochores attach to spindle microtubules">
          <outline text="Bi-orientation creates tension"/>
          <outline text="Attachment matters more than alignment"/>
        </outline>
        <outline text="Spindle-assembly checkpoint blocks anaphase">
          <outline text="Anaphase-promoting complex targets securin"/>
          <outline text="Separase cleaves cohesin"/>
        </outline>
        <outline text="Contractile ring and abscission"/>
        <outline text="Errors: tetraploidy, micronuclei, aneuploidy"/>
      </outline>
      <outline text="Meiosis">
        <outline text="One replication, two divisions"/>
        <outline text="Homologues recombine in first prophase">
          <outline text="Recombination aids correct segregation"/>
        </outline>
        <outline text="Meiosis one separates homologues"/>
        <outline text="Meiosis two separates sisters"/>
        <outline text="Maternal arrest raises aneuploidy with age"/>
      </outline>
      <outline text="Quiescence and stem cells">
        <outline text="Quiescence is active and often reversible"/>
        <outline text="Neurons and cardiomyocytes rarely cycle"/>
        <outline text="Symmetric divisions expand or deplete pool"/>
        <outline text="Asymmetric outcome keeps one stem-like daughter"/>
        <outline text="Transit-amplifying cells divide briefly"/>
        <outline text="Potency: totipotent, pluripotent, multipotent">
          <outline text="Induced pluripotent cells model disease"/>
        </outline>
        <outline text="Niche signals maintain stem-cell behaviour"/>
      </outline>
      <outline text="Senescence, telomeres, and cell death">
        <outline text="Senescence is durable proliferation arrest">
          <outline text="Secretory phenotype: cytokines, proteases"/>
          <outline text="Acute helps, chronic drives inflammation"/>
        </outline>
        <outline text="Short telomeres trigger damage response">
          <outline text="Not a simple biological clock"/>
        </outline>
        <outline text="Apoptosis without immediate membrane rupture">
          <outline text="Intrinsic: cytochrome c activates caspases"/>
          <outline text="Extrinsic: death receptors"/>
        </outline>
        <outline text="Regulated necrosis: necroptosis, pyroptosis, ferroptosis"/>
      </outline>
      <outline text="Observing cells">
        <outline text="Bright-field, phase-contrast, fluorescence"/>
        <outline text="Confocal sectioning and super-resolution"/>
        <outline text="Electron microscopy needs fixed specimens"/>
        <outline text="Colocalisation does not prove interaction"/>
        <outline text="Controls: positive, negative, no primary antibody"/>
        <outline text="Flow cytometry measures DNA content">
          <outline text="Gap two and mitosis not separated"/>
          <outline text="Histone H three phosphorylation marks mitosis"/>
        </outline>
      </outline>
      <outline text="Models and perturbation">
        <outline text="Primary cells short-lived, lines may be misidentified"/>
        <outline text="Plastic imposes unnatural stiffness"/>
        <outline text="Organoids and chips remain incomplete"/>
        <outline text="Loss- and gain-of-function tools">
          <outline text="Off-target effects and compensation"/>
          <outline text="Rescue strengthens causal inference"/>
        </outline>
        <outline text="Single-cell analysis reveals heterogeneity"/>
      </outline>
    </outline>
  </body>
</opml>
