Cellular and Molecular Bases of Biological Clocks

1. Introduction.- 1.1 Temporal Organization.- 1.2 General Properties of Circadian Rhythms.- 1.3 Analogies with Shorter Periodicities.- 1.3.1 An Atlas of Cellular Ultradian Periodicities.- 1.3.2 The Glycolytic Oscillator.- 1.3.3 Rhythmic Flashing of Fireflies.- 2. Circadian Organization in Eukaryotic Microorganisms.- 2.1 Circadian Rhythms in Protozoa.- 2.1.1 Tetrahymena spp.- Rhythms of Cell Division.- Physiological Rhythms Observed During the Infradian Growth Mode.- Circadian Rhythmicity in Metabolism and Biochemistry.- 2.1.2 Paramecium spp.- 2.2 Circadian Rhythms in Unicellular Algae.- 2.2.1 Acetabularia spp.- 2.2.2 Chlamydomonas spp.- 2.2.3 Euglena spp.- Circadian Rhythms of Cell Division.- Circadian Rhythms of Cell Motility.- Rhythm of Phototaxis.- Dark Motility Rhythm (Dunkelbeweglichkeit).- Rhythm of Cell Settling.- Rhythms in Photosynthetic Capacity.- Rhythm in Cell Shape.- Oscillatory Enzymatic Activities.- 2.2.4 Gonyaulax spp.- Circadian Rhythms in Bioluminescence: Physiological Characteristics.- Circadian Rhythms in Photosynthesis.- 2.3 Circadian Rhythms in Fungi.- 2.1.1 Neurospora spp.- The Rhythm of Conidiation.- Expression in Various Strains.- Light Effects.- Temperature Effects.- Other Factors.- Rhythm of Carbon Dioxide Production.- Rhythm in Adenylate and Pyridine Nucleotides.- Rhythms in Nucleic Acid Metabolism.- Rhythms in Enzymatic Activities.- Rhythms in Synthesis of Heat-Shock Proteins.- Rhythms in Fatty Acids.- 2.1.2 Saccharomyces spp.- 3. Cell Cycle Clocks.- 1.1 Regulation of the Cell Division Cycle.- 1.1.1 Probabilistic Models.- 1.1.2 Deterministic Models.- Dependent Pathways.- Cell Sizers.- Autonomous Timers: Cell Cycle Clocks and Oscillators.- Relaxation Oscillators.- Limit Cycle Oscillators.- Quantal Cell Cycles.- 3.2 Cell Division Cycles and Circadian Oscillators.- 3.2.1 Interaction of Circadian Oscillators with the Cell Cycle.- Circadian Oscillators and the CDC in Phytoplankton and Other Unicells.- Circadian Clock Control of the CDC in Euglena.- Entrainability.- Persistence.- Initiation.- Phase Shiftability.- Singularity Point.- Temperature Compensation.- Circadian Rhythms of Mammalian Cell Proliferation.- 3.2.2 Ultradian, Circadian, and Infradian Interfaces.- The Characteristics of the Oscillator.- Insertion and Deletion of Time Segments in Cell Cycles.- The Circadian-Infradian Rule.- 4. Experimental Approaches to Circadian Clock Mechanisms.- 4.1 Quest for an Anatomical Locus: Autonomous Oscillators in Isolated Organs, Tissues, and Cells.- 4.1.1 Circadian Pacemakers at the Organ and Tissue Levels.- The Hypothalamus.- Gastropod Eyes.- The Pineal Gland.- Pineal Biochemistry.- Pineal Physiology and Circadian Organization.- Pineal Pacemakers In Vitro.- Other Animal Organs and Tissues.- Plant Pulvini and Stomata.- 4.1.2 Circadian Rhythms in Isolated Cells.- 4.1.3 Subcellular Circadian Rhythmicity.- 4.2 Tracing the Entrainment Pathway for Light Signals.- 4.2.1 Nature and Localization of the Photoreceptor.- Plant Photoreceptors.- Photoreceptors in Animals.- 4.2.2 Coupling Links Between Receptor and Clock.- Light-Blocking Experiments.- Light-Mimicking Experiments.- Entrainment Pathway for Serotonin.- 4.3 Dissection of the Clock: Perturbation by Chemicals.- 4.3.1 Nonspecific Compounds and Respiratory.- Inhibitors.- Early Studies: The Chemical Shelf.- Deuterium Oxide.- Respiratory Inhibitors.- Energy Charge.- 4.3.2 Inhibitors of Macromolecular Synthesis.- Transcription of DNA.- Translation and Protein Synthesis.- Acetabularia.- Gonyaulax.- Neurospora.- Aplysia.- 4.3.3 Membrane-Active Agents.- Alcohols.- Fatty Acids.- Ions.- Potassium and Other Monovalent Ions.- Calcium.- Membrane ATPases.- Cyclic AMP.- 4.1 Dissection of the Clock: Molecular Genetics.- 4.4.1 Isolation of Clock Mutants.- Chlamydomonas.- Neurospora.- Drosophila.- Circadian Clock Mutants.- Ultradian Clock Mutants.- 4.4.2 Recombinant DNA Studies: Cloning Clock Genes.- Isolation of a Clock Gene.- Restoration of Biochemical Rhythms in Transgenic Drosophila.- The Product of the per Locus.- Molecular Analysis of Neurospora Clock Genes.- 4.4.3 Alteration of Clock Properties in Biochemical.- Mutants.- Respiratory and Photosensitive Pigments.- Cyclic AMP.- Fatty Acid Metabolism and Other Biosynthetic Pathways.- Oligomycin and Cycloheximide Resistance.- 4.5 Characterizing the Coupling Pathway: Transducing Mechanisms Between Clocks and Their Hands.- 4.5.1 Rhythms of Bioluminescence in Gonyaulax.- 4.5.2 Rhythms of Photosynthesis in Gonyaulax.- 5. Biochemical and Molecular Models for Circadian Clocks.- 5.1 In Vitro Molecular Models.- 5.2 Biochemical Feedback Loop and Network Models.- 5.2.1 Ultradian Metabolic Oscillators.- The Glycolytic Oscillator in Yeast.- Elements of the Oscillator.- Modeling Circadian Clocks with a Glycolytic-Type Oscillator.- The Cyclic AMP Oscillator of the Cellular Slime Mold.- 5.2.2 Cell Energy Metabolism.- Energy Charge.- The Deposition Effect and the Generation of Circadian Periods.- Temperature-Compensated Ultradian Clocks in Respiration.- 5.2.3 Coupled Oscillators.- 5.2.4 Periodic Enzyme Synthesis and Other Cyclic.- Epigenetic Events.- Periodic Enzyme Synthesis.- Self-Sustained Enzyme Oscillations.- Models of Microbial Enzyme Synthesis.- Other Cyclic Epigenetic Events.- 5.2.5 Circadian Biochemical Oscillators.- Cyclic AMP Models.- Models Based on the Mitochondrial Calcium Cycle.- 5.2.6 Infradian Metabolic Oscillators.- Regulation of Metabolic Pathways in Noncircadian Sporulation Rhythms.- Seasonal Rhythms and Photoperiodism.- 5.1 Transcriptional (Tape-Reading) Models.- 5.3.1 Specificity and Antispecificity Factors in Time Metering.- 5.3.2 The Chronon Model.- 5.3.3 Chronogenes and Cell Division Cycles.- 5.2 Membrane Models.- 5.4.1 Early Membrane Models.- 5.4.2 Coupled Translation-Membrane Model.- 5.4.3 Monovalent Ion-Mediated Translational Control Model.- 5.4.4 Other Variations on the Membrane Model Theme.- 5.3 Problems and Prospects.- 6. General Considerations and Conclusions.- 6.1 Evolution of Circadian Rhythmicity.- 6.1.1 Early Selection for Biological Clocks.- 6.1.2 Ultradian Clocks: Small Steps Toward Circadian Oscillators?.- 6.2 Multiple Cellular Oscillators.- 6.2.1 Intracellular Clockshops.- 6.2.2 Intercellular Communication and Coupled Oscillators.- 6.3 The Breakdown of Temporal Organization at the Cellular Level.- 6.3.1 Dysfunction of Cellular Pacemakers in Pathology and Disease.- The Cardiac Pacemaker.- Tremor.- Epilepsy.- Aging Clocks?.- 6.3.2 Cancer: The Malignant Transformation.- 6.4 Cellular Aspects of Chronopharmacology and Chronotherapy.- 6.5 Cellular Clocks in Development and Aging.- 6.5.1 Timing of Developmental Events.- 6.5.2 Spatial and Temporal Morphogenetic Fields.- 6.5.3 Aging: Life Cycle Clocks?.- 6.6 Epilogue.- References.- Author Index.