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CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK JET LAG -Resetting the clock by exposure to light at either dusk or dawn. -East to West: Later dusk, delay of clock. -West to East: Earlier dawn, advance of clock. -Resetting by drugs -Protein synthesis inhibitors: Causes phase-shifts (DRCs). -Protein phosphorylation and dephos: Causes period changes. SHIFT WORK; ACCIDENTS AND PERFORMANCE AT NIGHT -Many shift workers do not shift their biological clock. But alertness and task performance follows phase of the unshifted rhythm. -Single vehicle truck and car accidents and fatalities. Three Mile Island, Chernobyl, Exxon Valdez. CHRONOTHERAPY -DSPI: Delayed Sleep Phase Insomnia. Failure of advance phase shifts. -ASPI: Advance Sleep Phase Insomnia. Failure of delay phase shifts -SAD: Seasonal Affective Disorder. Day length. -Timing of drug administration; chronopharmacology; LD 50s

CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK JET LAG -Resetting the clock by exposure to light at either dusk or dawn. -East to West: Later dusk, delay

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Page 1: CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK JET LAG -Resetting the clock by exposure to light at either dusk or dawn. -East to West: Later dusk, delay

CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK

JET LAG-Resetting the clock by exposure to light at either dusk or dawn.

-East to West: Later dusk, delay of clock.-West to East: Earlier dawn, advance of clock.

-Resetting by drugs-Protein synthesis inhibitors: Causes phase-shifts (DRCs).-Protein phosphorylation and dephos: Causes period changes.

SHIFT WORK; ACCIDENTS AND PERFORMANCE AT NIGHT-Many shift workers do not shift their biological clock. But alertness and task performance follows phase of the unshifted rhythm.-Single vehicle truck and car accidents and fatalities. Three Mile Island,

Chernobyl, Exxon Valdez.

CHRONOTHERAPY-DSPI: Delayed Sleep Phase Insomnia. Failure of advance phase shifts.-ASPI: Advance Sleep Phase Insomnia. Failure of delay phase shifts-SAD: Seasonal Affective Disorder. Day length.-Timing of drug administration; chronopharmacology; LD 50s

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TYPE O (strong) & TYPE 1 (weak) PRCs in Gonyaulax with and without CREATINE

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DRUG PRC for CYCLOHEXIMIDE, a PROTEIN SYNTHESIS INHIBITOR

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EFFECTS OF KINASE INHIBITORS ON PERIOD (TAU)

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EFFECT OF PROTEIN PHOSPHATASE INHIBITORS ON PERIOD

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EFFECT OF CREATINE (FROM DIFFERENT SOURCES) ON PERIOD

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CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK

JET LAG-Resetting the clock by exposure to light at either dusk or dawn.

-East to West: Later dusk, delay of clock.-West to East: Earlier dawn, advance of clock.

-Resetting by drugs-Protein synthesis inhibitors: Causes phase-shifts (DRCs).-Protein phosphorylation and dephos: Causes period changes.

SHIFT WORK; ACCIDENTS AND PERFORMANCE AT NIGHT-Many shift workers do not shift their biological clock. But alertness and task performance follows phase of the unshifted rhythm.-Single vehicle truck and car accidents and fatalities. Three Mile Island,

Chernobyl, Exxon Valdez.

CHRONOTHERAPY-DSPI: Delayed Sleep Phase Insomnia. Failure of advance phase shifts.-SAD: Seasonal Affective Disorder. Day length.-Drug administration; chronopharmacology; LD 50s

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TIMES OF SINGLE VEHICLE TRUCK ACCIDENTS

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MYOCARDIAL INFARCTIONS AT DIFFERENT TIMES OF DAY

Page 10: CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK JET LAG -Resetting the clock by exposure to light at either dusk or dawn. -East to West: Later dusk, delay

CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK

JET LAG-Resetting the clock by exposure to light at either dusk or dawn.

-East to West: Later dusk, delay of clock.-West to East: Earlier dawn, advance of clock.

-Resetting by drugs-Protein synthesis inhibitors: Causes phase-shifts (DRCs).-Protein phosphorylation and dephos: Causes period changes.

SHIFT WORK; ACCIDENTS AND PERFORMANCE AT NIGHT-Many shift workers do not shift their biological clock. But alertness and task performance follows phase of the unshifted rhythm.-Single vehicle truck and car accidents and fatalities. Three Mile Island,

Chernobyl, Exxon Valdez.

CHRONOTHERAPY-DSPI: Delayed Sleep Phase Insomnia. Failure of advance phase shifts.-SAD: Seasonal Affective Disorder. Day length.-Drug administration; chronopharmacology; LD 50s

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DELAYED SLEEP PHASE INSOMMNIA THERAPY

Deficiency in advance phase shifts

Treatment: Impose repeated delaysuntil patient is back in phase.

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IS THE CIRCADIAN CLOCK NECESSARY ?

DOES THE CLOCK CONFER SELECTIVE ADVANTAGE?

MEASURE LIFESPAN IN ANIMALS SUBJECTED TO NON-24 hr CYCLES

RESONANCE EXPERIMENTS IN CYANOBACTERIA USING PERIOD MUTANTS

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SURVIVIAL CURVES FOR FLIES IN LIGHT/DARK CYCLES WITH PERIODS OF 20, 24 AND 28 HOURS

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FIVE HOUR LD PHASE SHIFTS EACH CYCLE

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MUTANTS V.S. WILD TYPE IN DIFFERENT LD CYCLES

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MUTANT TAU-28 V.S. WILD TYPE

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SOME FUNCTIONS OF THE CIRCADIAN CLOCK

TIME ACTIVITIES: CERTAIN TIMES OF DAY/NIGHTInsect eclosion acrophase is at time of daily temperature minimum.

The internal bee clock; Visitations timed to time of flower openingsCyanobacteria, photosynthesis by day, nitrogen fixation by night.

CELESTIAL NAVIGATION-Animal migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

PHOTOPERIODISM: MEASURE DURATION OF DAY AND NIGHT-Plant rhythms: seasonal flowering, spring, summer or fall.-Animal seasonal reproduction; hamster only once per year.

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DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

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BEAN (top) and CANAVALIA CIRCADIAN LEAF MOVEMENTS

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TEMPORAL SEPARATION OF CELL BIOCHEMICAL ACTIVITIES IN CYANOBACTERIA (OXYGEN, NITROGENASE ETC) MITSUI ET AL 1986

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OXYGEN PRODUCTION(TOP) & NITROGENASE (BOTTOM) IN CYANOBACTERIA IN LD (LEFT) &LL (RIGHT) Stal & Krumbeing, 1987

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SOME FUNCTIONS OF THE CIRCADIAN CLOCK

TIME ACTIVITIES: CERTAIN TIMES OF DAY/NIGHTInsect eclosion acrophase is at time of daily temperature minimum.

The internal bee clock; Visitations timed to time of flower openingsCyanobacteria, photosynthesis by day, nitrogen fixation by night.

CELESTIAL NAVIGATION-Animal migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

PHOTOPERIODISM: MEASURE DURATION OF DAY AND NIGHT-Plant rhythms: seasonal flowering, spring, summer or fall.-Animal seasonal reproduction; hamster only once per year.

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DIRECTION OF STARLING MIGRATORY ACTIVITYKramer,1950 a) clear sky b)overcast c),d) direction of incident light deflected by mirrors

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DIRECTION OF DEPARTURE IN PIGEONS ALTERED AFTER EXPOSURE TO LD CYCLE ALTERED BY 6 hr Schmidt-Koenig,1961

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SHIFTING THE DIRECTIONAL RESPONSE OF PIGEONS

Page 29: CHRONOBIOLOGICAL APPLICATIONS OF CIRCADIAN CLOCK JET LAG -Resetting the clock by exposure to light at either dusk or dawn. -East to West: Later dusk, delay

SOME FUNCTIONS OF THE CIRCADIAN CLOCK

TIME ACTIVITIES: CERTAIN TIMES OF DAY/NIGHTInsect eclosion acrophase is at time of daily temperature minimum.

The internal bee clock; Visitations timed to time of flower openingsCyanobacteria, photosynthesis by day, nitrogen fixation by night.

CELESTIAL NAVIGATION-Animal migration (birds, butterflies, arthropods, fish, reptiles); knowledge of time of day required.

PHOTOPERIODISM: MEASURE DURATION OF DAY AND NIGHT-Plant rhythms: seasonal flowering, spring, summer or fall.-Animal seasonal reproduction; hamster only once per year.

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DAY LENGTH AT DIFFERENT LATITUDES & SEASONS

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CIRCANNUAL RHYTHMS IN SQUIRRELS & GONYAULAX

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ANNUAL RHYTHM OF HUMAN REPRODUCTION Roenneberg & Aschoff,1990

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PHOTOPERIODISM

DISCOVERY: Garner & Allard, 1920

TOBACCO FLOWERING ONLY IN FALL WITH SHORT DAYS OTHER PLANTS SHOWN TO FLOWER WITH LONG DAYS. STILL OTHERS DAY LENGTH NEUTRAL

TERMINOLOGY CORRECTED: Hamner & Bonner, 1938

LENGTH OF THE NIGHT, NOT THE DAY, IS CRITICAL LIGHT INTERRUPTIONS OF NIGHT BLOCK RESPONSE, DARK INTERRUPTIONS OF DAY DO NOT BLOCK

INCORRECT TERMINOLOGY STILL IN USE:

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HAMSTER TESTIS WEIGHT IN DIFFERENTFULL PHOTOPERIODS Elliott, 1976

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PHOTOPERIODIC INDUCTION OF CYSTS IN GONYAULAX

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SOY BEAN (SHORT DAY PLANT) 0.5 hr LIGHT INTERRUPTION OF LONG DARK PERIOD WARING, 1954

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H. NIGER (LONG-DAY PLANT) 2 hr LIGHT INTERRUPTION OF LONG DARK PERIOD

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SOYBEAN FLOWERING IN DIFFERENT LD CYCLES

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MODELS FOR PHOTOPERIODISM

HOUR GLASS: Substance X builds up during dark

Explains night interruption

Does not explain oscillation of long dark periods.

ENDOGENOUS OSCILLATION

External Coincidence model: Large delays & advances

Internal Coincidence model: Light cycle entrains. Response is caused by interaction between two internal oscillators, pacemaker and slave.

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EXTERNAL COINCIDENCE: POSTULATED PHOTOPERIODIC EFFECTS ON AN ORGANISM WITH A CIRCADIAN TAU OF 24.5 hr

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ENTRAINMENT TAU OF HAMSTER ACTIVITY RHYTHM DEPENDS ON PERIOD OF SINGLE PULSE T CYCLE AND

PULSE IS POSITIONED DIFFERENTLY Elliott 1976

Tau for hamster is very close to 24 h

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TESTICULAR RESPONSES TO ONE PULSE T CYCLE LENGTH

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DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

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BISTABILITY IN 2-PULSE SKELETON PHOTOCYCLES (Pittendrigh;Drosophila)

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PHASE ANGLES WITH DIFFERENT TWO PULSE SKELETONS Pittendrigh

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BISTABILITY IN HAMSTER ENTRAINMENT SKELETON PHOTOPERIOD 13.5:0.25:10:0.25 hrs

ANIMAL C15 ACTIVE INSHORT NIGHT TESTES MAINTAINED; ANIMAL C16 ACTIVE IN LONG NIGHT; TESTES REGRESSED

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SKELETON PHOTOPERIOD PHASING GIVES DIFFERENT RESPONSES