INTRODUCINGBIOLOGICAL RHYTHMS

A Primer on the Temporal Organization of Life,with Implications for Health, Society, Reproduction

and the Natural Environment

Willard L. Koukkari and Robert B. SothernCollege of Biological Sciences

University of MinnesotaSt. Paul, MN, USA

4y Springer

Contents

Preface viiAcknowledgments ix

1 The Study of Biological RhythmsIntroduction 1A Time for Everything 4Three Rhythm Domains 6Implications of Body Clocks 11

Essay 1.1: Accidents and Catastrophes 11Chronobiology: An Integrating Discipline 12Chapters in This Book 14Take-Home Message 15

2 General Features of Rhythms: Terminology and CharacteristicsIntroduction 19Details of a Rhythm 20

Period and Frequency 21Orcadian Domain 21Essay 2.1: Use of the term "Orcadian" 23Other Domains 25Ev.vav 2.2: Time on Earth as We Know It 26Amplitude 29Phase 29

Genetics and Inheritance 29Period 30Amplitude and Phase 30

Primary Orcadian Clocks 32The Brain 33SCN Identification 34SCN as Synchronizer 36Retinal Melanopsin 36Retinohypothalamic Tract 37

XI

xii Contents

Characteristics of the Period 38Stability and Free-Running 38Frequency Multiplication/Demultiplication 39Light Quali ty 40Temperature 41Chemicals 42

Characteristics of the Amplitude 42Damping 43

Characteristics of the Phase 44Synchronizers 44Phase-Shifting by Light 44Phase Shifts by Chemicals or Temperature 45Phase-Response Curve 46

Masking 47Need for a Cyclic Environment 48In Darwin's Footsteps 49

Exercise 2.1: An Ultradian Experiment: 52Circumnutation

Exercise 2.2: A Orcadian Experiment: 54Leaf Movements

Mechanisms 56Take-Home Message 56

3 Physical a n d Biological TimeIntroduction 66Rotations a n d Revolutions of the Earth and Moon 67

The Day 68The Year 69The Month 71

Clocks and Calendars: Ancient Times 72The Month and Year 72The Day 77The Week 78

Clocks and Calendars: Middle Ages to Now 79Longitude and Clocks 8 0

Springs to Atoms 8 2

Essay 3.1; Wristwatches 83Time Zones 8

Daylight Saving Time 85Recording Date and Time 8 5

Recording Biological Time 86The 24-h Biological Clock Concept 8 7

Early Studies 8 7

Considerations 8^

Contents xiii

Ultradian and Infradian Clocks 89Endogenous vs. Exogenous 90Comparison with Manufactured Clocks 90

Evolution of the Clock 92Molecular Building Blocks 93Geological History and Rhythmic Components 95Adaptation to Avoid Harmful Light 99Ancestral Traits and Convergent Evolution 101

Take-Home Message 102

4 PhotoperiodismIntroduction 107Daylight and Seasons 107Photoperiodism: The ProcessResponse Types 113

Critical DaylengthDiversity of Responses.

Early StudiesLatitude.

s.Light and Photoreceptive RegionsExtraretinal Photoreceptors .PigmentsCryptochromesSpectra

Rhvthmic Association.Endogenous Oscillators..Biinning's HypothesisPhase-Response Curves .Ultradian CyclesCircannual CyclesBird MigrationDeer AntlersVernalization

Photoperiodism and HumansBirth PatternsIndoor vs. Outdoor Light.Disorders

Take-Home Message

14151616171819

2123232525252626282829293030•p

5 Biological Oscillators and Timers: Models and MechanismsIntroduction 13SApproaches to Models and Mechanisms 139Mechanical Models 141

Pendulum 142

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Hourglass 142External Coincidence 143Hands of a Clock 144

Mathematical Models 145Differential Equations 148Limit Cycles and Topography 149Chaos 153Spatiotemporal Systems 153

Biochemical and Metabolic Models 155Chemical Systems 155Biochemical Systems 155Essay 5.1: Selected Biochemical Notes 156Glycolytic Oscillations 157Nucleotides and Enzymes 158

Membrane Models 158Essay 5.2: Membranes and the Phospholipid Bilayer 159Lipids and Proteins 163Transport and Feedback 165

Molecular Models 167Essay 5.3: From Genes to Proteins and Mutants 167Genes and Nomenclature 171Clock Mutations 173Circadian: System and Clock 173Transcription/Translation Feedback Loops 174Light 177Temperature 178Five Circadian Clocks 179Neurospora Circadian Clock 179Advantages 179Overt Rhythms 179Genetic Highlights 181Feedback Loops and Components 181Drosophila Circadian Clock 181Advantages 182Overt Rhythms 183Genetic Highlights 183Feedback Loops and Components 183Mammalian Circadian Clock 184Advantages 184Overt Rhythms 184Genetic Highlights 184Feedback Loops and Components 186Arabidopsis Circadian Clock 187Advantages 187Overt Rhythms 187

Contents xv

Genetic Highlights 187Feedback Loops and Components 187Cyanobacteria Circadian Clock 189Advantages 190Overt Rhythms 191Genetic Highlights 191Feedback Loops and Components 191Models in Perspective 192Generalized Schematic Model for 192

Biological RhythmsTake-Home Message 193

6 Tidal and Lunar RhythmsIntroduction 207Moon and Light 208Moon and Tides 210

High and Low Tides 210Spring and Neap Tides 214Earth Tide 214Essay 6.1: Earth Tides 214

Marine Organisms 216Circatidal Rhythms 216Crab Activity 217Circadian vs. Circatidal 218Other Organisms 219Reproduction 220Color Change 224

Terrestrial Organisms 226The Menstrual Cycle 227Atmospheric Tides 227Insects 228

Plants 228Lunar/Tidal Clock Hypotheses 229

Circadian vs. Circalunidian 229Interacting Oscillators'.' 230

Take-Home Message 231

7 Sexuality and ReproductionIntroduction 237

Essay 7.1: Parasexuality 238Nuclear Division and Genetics 240

Es.sav 7.2: Mitosis. Meiosis. and 240the Punnett Square

Sex and Reproduction: The Difference 250

xvi Contents

Essay 7.3: Artificial Hybridization and 251How Sex Produces both "Lunch"and an Embryo

Asexual Reproduction 255Essay 7.4: An Abbreviated Life History of 256

Neurospora crassaCourtship and Mating 257

Photoperiodism and Sexuality 259Diet 259Flowers 260

Rhythmic Phases of Sexual Behavior in Humans 261Activity 261Disease 261

The Menstrual Cycle 262Duration and Phase 262Essay 7.5: Brief Physiology of Menstrual Cycle 262

Events and PhasesSocial Synchronization 268Sexual Activity and Birth Control 268

Primary and Secondary Sex-Related Rhythms in Men 272Ultradian and Circadian Cycles 272Infradian Cycles 273

Essay 7.6: 17th Century Notes of Monthly 273Rhythms in Males

Body Weight 274Grip Strength 274Cutaneous Pain 277Hormones 277Essay 7.7: More About Infradians 277

in Male HormonesEmotions 278Facial Sebum 279Beard Growth and Body Hair 280Sexual Activity 282

Take-Home Message 284

8 Natural Resources and AgricultureIntroduction 293Photoperiodism 294

Essay S.I: Photoperiodism as a Basic 294Principle of Biology and Its Applications

Thermoperiodism and Temperature Cycles 297Vernalization 298Temperature Compensation 300

Migration 300

Contents xvii

Birds 301Butterflies 302

Pest Management and Agents of Stress 304Herbicides 304Pest Control 306Plant Responses to Injury 307Plant Diseases 308

Production of Produce 309Fisheries and Aquaculture 310Weather Patterns and Agriculture 313

Gardens 313Outdoor Hobbies 317

Birding 317Fishing 318Essay 8.2: Fly-fishing for Trout 318

Rural and Urban Development 322Telemetry Tracking Systems 324Muskrats 324Squirrels and Foxes 324Hare 324Ruffed Grouse 326The Outdoor Laboratory 327Temporal Agroecosystems 327

Light Pollution 328Aquatic Animals 328Vertical Migration 329Drift 330Trout 330Turtles 331Insects 331Birds 332

Take-Home Message 332

9 Veterinary MedicineIntroduction 341Body Temperature and Activity 342

Diurnal vs. Nocturnal 343Timing of Food 344Masking 346Environment 346Cattle USDogs and Cats 348Poultry 349

Hematology and Urology 349Sampling Blood 349

xviii Contents

Multiple Rhythms 349Peak Times 351Collecting Urine 351Excretion Rates 353Urinary Rhythms 354Interpreting a Sample 354

A Primary Circadian Oscillator 355The Suprachiasmatic Nucleus 356The Pineal Gland 356

Diseases, Pests, and Stress 357Parasites 357Bacterial Infections 358Seasonal Diseases 358Flies 359Fleas 360

Reproduction and Photoperiodism 360Photoperiod 361Melatonin 361Domestic Fowl 362Sheep 363Horses 364Pigs and Goats 365Artificial Insemination 365Semen Quality and Season 365

Implications 366Take-Home Message 366

10 SocietyIntroduction 376Past and Present 377

The Natural Day vs. 24/7 377Time Schedules 378

Social Synchronization 380Essay 10.1: Social Synchrony in 380

AnimalsCircadian Events 381Ultradian and Infradian Events 384

Aggression and Violence 384Night and Shiftwork 385

Time for Sleep 385Problems with Shiftwork 386Adjusting to Shiftwork 387

The Global Workplace 388Communication 388Work Schedules and Outsourcing 389

Contents xix

Sports and Performance 389Body Temperature and Performance Variables 391A Time to Train or Win 391Jet Lag and Professional Sports 392Allowing for Jet Lag 392

Travel on the Earth's Surface 393Driver Fatigue and Vehicle Accidents 394Alcohol, Driving, and Fatigue 395The Post-Lunch Dip 396Animal Activity and Vehicle Accidents 396

Travel Above the Earth's Surface 396Jet Lag 397Life in Space 398

Travel Beneath the Seas 399Mealtimes and Health 401

Essay 10.2: Preclinical Meal-Timing Studies 402Changes in Body Weight and Rhythms 404Food: What, How Much, and When 408

Light Pollution 408Effects on Melatonin Production 409Effects on Clinical Health 410Better Lighting Practices 411

Pseudoscience: Birthdate-Based Biorhythms 412Essax 10.3: Development of the Biorhythm 412

"Theory"Lack of Scientific Support 413Rigidity vs. Elasticity of Infradian Periods 414An Oversimplification of Rhythms 414

Take-Home Message 415

11 Clinical MedicineIntroduction 426Circadian Rhythms in Health 437

Essay 1 I.I: Adjusting Urinary Concentrations 438for Volume and Time

Overview of Rhythms in Body Systems 430What and When is Normal? 433Time-Specified Normal Limits 438

Circadian Rhythms in Symptoms and Disease 441Birth and Death 442Cardiovascular Disease 443

Circannual Rhythms in Health 445Orcannual Rhythms in Symptoms and Disease 446

Cardiovascular Disease 448The Coagulation System 449

xx Contents

Cholesterol 450Respiratory Illness 452Mental Disorders 452Seasonal Affective Disorder 452

The Menstrual Cycle 453Disorders 454Medical Procedures 455Male Cycles 455

Melatonin and Human Health 456Darkness and Melatonin 456Sexuality 458Immune Function 459Light, Melatonin and Cancer 460Light Leaks at Night 461

When to Sample? 462Diagnosing Normal Levels 463Diagnosing Infectious Agents 464Diagnosing Abnormal Levels 467Using Rhythm Characteristics in Diagnosis 467

Hours of Changing Resistance 470Early Pre-Clinical Findings 471Time-Related Responses to 471

Anti-Cancer DrugsStage of Rhythm vs. Time of Day 473Varying Positive or Negative Effects 473

Timing Treatment: Chronotherapy 475Three Times a Day? 476Constant Dosing 476Rhythm-Dependent Effects of Some Drugs 478Administering Chronotherapy 478

Examples of Applied Chronotherapy 480Asthma 481Cancer-Animal Studies 482Cancer-Human Trials 484

Cellular Clocks and Chronotherapy 486Time-Indicating Genes 487Molecular Machinery Underlies Physiology 487

Marker Rhythms 488The Medical Community and the Concept of Timing 489Take-Home Message 491

12 AutorhythmometryIntroduction 526Measuring Your Own Body Rhythms 527

Schoolchildren 528

Contents xxi

Adults 529Performance 529Ultradian Rhythms 529Self-help Health Care 529Monitoring Symptoms 530

Body Temperature 530Internal Marker Rhythm 531Measurement Site 532What and When is Normal? 533

Blood Pressure 534Monitoring Hypertension 534Ambulatory Monitoring 535

Morningness-Eveningness 535Questionnaires 535Morningness vs. Life Factors 536Endogenous Disposition 536Body Temperature Phase 536Cognitive Tasks 537

When and How Long to Measure? 537Self-Measurements During Travel 537Self-Measurements During Isolation 540Essay 12.1: Self-Measurements in 540

"Aschoff's Bunker"Long Self-Measurement Series 544

What can be Self-Measured? 545Equipment 545

Internal or External Body Temperature 546Temperature Devices 547Blood Pressure Devices 550Automatic Devices 550Other Equipment 552Saliva, Urine, and Blood 555

Procedures for Self-Measurements 555Keeping Records 555Sampling Sequence 555

Looking at the Data 556Making Graphs 556Testing for a Time-Effect 557

Take-Home Message 558Appendix

Item I: Sample sheet for recording oral 568temperature and other functions

Item 2: Sample sheet for recording and 569graphing temperature, pulse andblood pressure

xxii Contents

Item 3: Detailed instructions for performing 570self-measurements

Item 4: Random Number Adding Speed Test 572sample pages

Item 5: Random Number Memory Test 574sample pages

13 Chronobiometry: Analyzing for RhythmsIntroduction 577Data Collection 578

Number of Timepoints 579How Long? 580Sampling Often Enough 580Aliasing 580Decision Making 580

Data Preparation 582Graphs and Visual Inspection 582Editing or Transforming Data 583Essay 13.1: Standard Deviation and Error 584Normalizing Data 584Partitioning Data Spans 585

Statistical Detection of Time Effects 586Using Two Timepoints 586Using Three or More Timepoints 586

Statistical Detection of Rhythms 588Analyzing Time-Series by Standard Methods 588Limitations of Standard Methods 588Analyzing Time-Series by Curve Fitting 589The Least-Squares Technique 590The Best-Fitting Curve 591Statistical Significance 592Complex Waveforms 592Rhythm Parameter Comparisons 593Lack of Rhythm Detection 593

Descriptive Rhythm Parameters 595The Cosinor Illustrated 596

Example of a Cosinor Program 596Take-Home Message 600

Author Index 603Subject Index 649