Sleep cleans your brain Fig 1 Wakefulness suppresses
Sleep cleans your brain! Fig. 1: Wakefulness suppresses influx of CSF tracers. (B) Three-dimensional (3 D) vectorized reconstruction of the distribution of CSF tracers injected in a sleeping mouse and then again after the mouse was awakened. The vasculature was visualized by means of cascade blue-dextran administered via the femoral vein. FITC-dextran (green) was first injected in the cisterna magna in a sleeping mouse and visualized by collecting repeated stacks of z-steps. Thirty min later, the mouse was awakened by gently moving its tail, and Texas red-dextran (red) was administered 15 min later. The experiments were performed mostly asleep (12 to 2 p. m. ). The arrow points to penetrating arteries. (C) Comparison of time-dependent CSF influx in sleep versus awake. Tracer influx was quantified 100 μm below the cortical surface; n = 6 mice; *P < 0. 05, two-way ANOVA with Bonferroni test. (Right) The tracer intensity within the two arousal states at the 30 -min time point was compared. **P < 0. 01, t test. L. Xie et al. , Science 342: 373 -7, 2013
Biological Sciences Seminar Leslie Babonis, Ph. D Whitney Marine Lab University of Florida Novel genes, novel cells, and the evolution of diversity Friday, Jan 8 th 2016 3: 30 - 5: 00 p. m. UW 2 – 040 Coffee and snacks will be provided
BBio 351, January 6, 2016: Homeostasis & cell signaling Outline: 1. Homeostasis and its variations (Sherwood 1. 5 -1. 7) • Homeostasis via negative feedback • Variations: feedforward control, positive feedback 2. Cell signaling (Sherwood 3. 4) • Intercellular signaling • Intracellular signaling (signal transduction)
Homeostasis via negative feedback • “Homeo” + “stasis” = • In what sense is negative feedback “negative”? • 4 general components of a negative feedback system?
• Which endocrine/reproductive/nervous system variables are regulated via negative feedback? • Thyroid hormone levels in blood? • Melatonin levels in blood? • Glucose levels in blood? • Gonadotropin Releasing Hormone (Gn. RH) levels in blood? • Luteinizing Hormone (LH) levels in blood? • Membrane potential? • Stimulation of photoreceptors in eye?
• How robust should negative feedback be? • Example: blood glucose levels [Glucose] in mg/d. L 1 2 3 4 5 Time in hours
• How robust should negative feedback be? Function of insulin = Function of glucagon = [Glucose] in mg/d. L 1 2 3 4 5 Time in hours
Variations on negative feedback: positive feedback Sherwood Fig. 1 -10 b
Sherwood Figure 4 -7: Opening of voltage-gated Na+ channels
Variations on negative feedback: feedforward control Sherwood Figure 1 -9 b
Control of muscle glycolysis? • Glycolysis = • Feedback hypothesis • ATP levels are regulated • ATP breakdown products (ADP, Pi) stimulate ATP production by glycolysis • Feedforward hypothesis • Muscle contraction uses ATP • Muscle contraction signal stimulates glycolytic ATP production in anticipation of need for more ATP • Test of hypotheses • Ischemia: cut off O 2 flow to exercising muscles • Ischemia raises ADP and Pi … and glycolysis? K. E. Conley et al. , Journal of Physiology 1998
Control of muscle glycolysis? K. E. Conley et al. , Journal of Physiology 1998
Cell signaling • Signaling CHANGE • What causes a protein to change shape? • Intercellular signaling • Intracellular signaling (signal transduction)
Intercellular signaling F. Martini et al. , Fundamentals of Anatomy & Physiology (simpler version of Sherwood Fig. 3 -16)
Signal transduction across cell membrane • Ligand • Receptor • G protein • 2 nd messenger • Intracellular proteins
Structural classes of signal molecules • 3 main groups Shutter. Stock. com; Wikimedia; Wikipedia
Relative size Hydrophobic? Hydrophilic? Location of receptors (Cell surface? Interior? )
G proteins: key players in signal transduction Sherwood Figure 3 -17 c
2 nd messengers: c. AMP, c. GMP, Ca 2+, etc.
Components of signal transduction • Tyrosine kinase receptors • G proteins • Cyclic nucleotides (c. AMP, c. GMP) • Calcium (Ca 2+) • Transcription factors
Example of signal transduction: insulin receptors Sherwood Figure 3 -18
Example of signal transduction: glycogen breakdown
Example of signal transduction: phototransduction in photoreceptors of retina upload. wikimedia. org/wikipedia/commons/d/de/Phototransduction. png
Signal transduction: transcription factors
Sherwood Figure 3 -21 Amplification of signals
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