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

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

DRUG PRC for CYCLOHEXIMIDE, a PROTEIN SYNTHESIS INHIBITOR

EFFECTS OF KINASE INHIBITORS ON PERIOD (TAU)

EFFECT OF PROTEIN PHOSPHATASE INHIBITORS ON PERIOD

EFFECT OF CREATINE (FROM DIFFERENT SOURCES) ON PERIOD

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

TIMES OF SINGLE VEHICLE TRUCK ACCIDENTS

MYOCARDIAL INFARCTIONS AT DIFFERENT TIMES OF DAY

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

DELAYED SLEEP PHASE INSOMMNIA THERAPY Deficiency in advance phase shifts Treatment: Impose repeated delays until patient is back in phase.

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

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

FIVE HOUR LD PHASE SHIFTS EACH CYCLE

MUTANTS V.S. WILD TYPE IN DIFFERENT LD CYCLES

MUTANT TAU-28 V.S. WILD TYPE

SOME FUNCTIONS OF THE CIRCADIAN CLOCK TIME ACTIVITIES: CERTAIN TIMES OF DAY/NIGHT Insect eclosion acrophase is at time of daily temperature minimum. The internal bee clock; Visitations timed to time of flower openings Cyanobacteria, 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.

DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

BEAN (top) and CANAVALIA CIRCADIAN LEAF MOVEMENTS

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

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

SOME FUNCTIONS OF THE CIRCADIAN CLOCK TIME ACTIVITIES: CERTAIN TIMES OF DAY/NIGHT Insect eclosion acrophase is at time of daily temperature minimum. The internal bee clock; Visitations timed to time of flower openings Cyanobacteria, 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.

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

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

SHIFTING THE DIRECTIONAL RESPONSE OF PIGEONS

SOME FUNCTIONS OF THE CIRCADIAN CLOCK TIME ACTIVITIES: CERTAIN TIMES OF DAY/NIGHT Insect eclosion acrophase is at time of daily temperature minimum. The internal bee clock; Visitations timed to time of flower openings Cyanobacteria, 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.

DAY LENGTH AT DIFFERENT LATITUDES & SEASONS

CIRCANNUAL RHYTHMS IN SQUIRRELS & GONYAULAX

ANNUAL RHYTHM OF HUMAN REPRODUCTION Roenneberg & Aschoff,1990

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:

HAMSTER TESTIS WEIGHT IN DIFFERENT FULL PHOTOPERIODS Elliott, 1976

PHOTOPERIODIC INDUCTION OF CYSTS IN GONYAULAX

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

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

SOYBEAN FLOWERING IN DIFFERENT LD CYCLES

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.

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

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

TESTICULAR RESPONSES TO ONE PULSE T CYCLE LENGTH

DROSOPHILA ENTRAINMENT TO FULL LD CYCLES PITTENDRIGH

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

PHASE ANGLES WITH DIFFERENT TWO PULSE SKELETONS Pittendrigh

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

SKELETON PHOTOPERIOD PHASING GIVES DIFFERENT RESPONSES