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Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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Mechanism of Angiogenesis01:10

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Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
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Regulation of Angiogenesis and Blood Supply01:24

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Stimulants01:29

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Stimulants are substances that enhance neural activity and elevate dopamine levels in the brain, leading to their highly addictive nature. These drugs include cocaine, amphetamines, MDMA, caffeine, and nicotine, each with distinct mechanisms of action and varied health implications.
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Motor Unit Stimulation01:20

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When the neuron of a motor unit fires an action potential, it triggers a series of events, leading to a twitch contraction in the muscle fibers. The process of excitation-contraction coupling is crucial in relaying the action potential to the muscle fibers.
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Muscle Stimulation Frequency

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The contraction strength of muscles is regulated by motor neurons, which modulate the frequency of action potentials dispatched to the motor units based on the body's requirements. This process of varying the muscle stimulation frequency allows muscles to contract with a force that is precisely tailored to the needs of the moment, whether lifting a feather or a heavy box.
Wave summation
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In Vitro Model of Coronary Angiogenesis
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High mitogenic stimulation arrests angiogenesis.

Samuel Pontes-Quero1, Macarena Fernández-Chacón1, Wen Luo1

  • 1Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain.

Nature Communications
|May 3, 2019
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Summary
This summary is machine-generated.

High levels of vascular endothelial growth factor (VEGF) signaling paradoxically arrest, rather than promote, blood vessel growth. This discovery challenges current understanding and offers new therapeutic targets for angiogenesis.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Vascular Biology

Background:

  • Therapeutic modulation of endothelial cell proliferation and sprouting is critical for managing angiogenesis in diseases like cancer and cardiovascular conditions.
  • Current understanding suggests increased growth factor concentration directly correlates with enhanced endothelial proliferation and sprouting.

Purpose of the Study:

  • To investigate the precise effects of modulating vascular endothelial growth factor (VEGF) and Notch signaling pathways on endothelial cells in vivo.
  • To challenge the prevailing view on growth factor concentration and its impact on endothelial proliferation and sprouting.

Main Methods:

  • Interference with VEGF and Notch signaling pathways in vivo at high spatiotemporal resolution.
  • Analysis of endothelial cell behavior (sprouting, proliferation, quiescence) under varying mitogenic stimuli.

Main Results:

  • Contrary to expectations, high mitogenic stimulation via VEGF or Notch inhibition led to the arrest of angiogenic vessel proliferation.
  • A bell-shaped dose-response curve was identified for VEGF and MAPK activity, influencing endothelial cell fate.
  • Notch and p21 were found to counteract this response, determining whether endothelial cells sprout, proliferate, or enter quiescence.

Conclusions:

  • The study reveals a complex, non-linear relationship between mitogenic signaling and angiogenesis.
  • A novel mechanism involving a bell-shaped dose-response and counteracting factors (Notch, p21) dictates endothelial cell behavior.
  • This mechanism provides a new framework for optimizing therapeutic strategies targeting angiogenesis.