Transcript Fig. 1: Wakefulness suppresses influx of CSF tracers.

Sleep cleans your brain!
Fig. 1: Wakefulness suppresses influx of CSF tracers. (B) Three-dimensional (3D) 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, PhD
Whitney Marine Lab
University of Florida
Novel genes, novel cells, and the evolution of
diversity
Friday, Jan 8th 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 (GnRH) 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/dL
Time in hours
1
2
3
4
5
• How robust should negative feedback be?
Function of insulin =
Function of glucagon =
[Glucose]
in mg/dL
Time in hours
1
2
3
4
5
Variations on negative feedback: positive feedback
Sherwood Fig. 1-10b
Sherwood Figure 4-7: Opening of voltage-gated Na+ channels
Variations on negative feedback: feedforward control
Sherwood Figure 1-9b
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 O2 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
• 2nd messenger
• Intracellular proteins
Structural classes of signal molecules
• 3 main groups
ShutterStock.com; Wikimedia; Wikipedia
Relative size
Hydrophobic?
Hydrophilic?
Location of
receptors (Cell
surface? Interior?)
G proteins: key players in signal transduction
Sherwood Figure 3-17c
nd
2
messengers: cAMP, cGMP,
2+
Ca ,
etc.
Components of signal transduction
• Tyrosine kinase receptors
• G proteins
• Cyclic nucleotides (cAMP, cGMP)
• Calcium (Ca2+)
• 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