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E-Book

E-Book, Englisch, Band Volume 393, 968 Seiten, Web PDF

Reihe: Methods in Enzymology

Young Circadian Rhythms


1. Auflage 2005
ISBN: 978-0-08-045540-2
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band Volume 393, 968 Seiten, Web PDF

Reihe: Methods in Enzymology

ISBN: 978-0-08-045540-2
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark



The critically acclaimed laboratory standard, Methods in Enzymology, is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. The series contains much material still relevant today - truly an essential publication for researchers in all fields of life sciences. Circadian Rhythms contains an extensive discussion of genetic and biochemical aspects of circadian rhythms. In this volume organisms such as neurospora, bacteria, drosophila, arabidopsis and mammals are covered. Included are methods in genetics, transcriptional and post-transcriptional regulation, tissue culture, and populations are discussed in detail.* One of the most highly respected publications in the field of biochemistry since 1955 * Frequently consulted, and praised by researchers and reviewers alike * Truly an essential publication for anyone in any field of the life sciences

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1;front cover;1
2;copyright;5
3;Table of Contents;6
4;front matter;11
5;Contributors to Volume 393;11
6;Preface;17
7;body;42
8;Section I: Genetic Approaches to Circadian Clocks;42
8.1;[1] Analysis of Circadian Rhythms in Overview of Assays and Genetic and Molecular Biological Manipulation;44
8.1.1;Abstract 1;44
8.1.2;Introduction 1;44
8.1.3;Rhythms in Neurospora;45
8.1.4;Overview of Molecular Events in the Neurospora Circadian Cycle;46
8.1.5;Assays for Rhythmicity in Neurospora;48
8.1.6;Analysis via Genetic and Molecular Genetic Techniques;52
8.1.7;Concluding Remarks 1;59
8.1.8;References 1;60
8.2;[2] Circadian Genetics in the Model Higher Plant,;64
8.2.1;Abstract 2;64
8.2.2;Introduction 2;64
8.2.3;Circadian Screens Using Luciferase;66
8.2.4;Circadian Screen Measuring Stomatal Rhythms;73
8.2.5;Testing Circadian Rhythms of Mutants Identified in Other Screens;73
8.2.6;Reverse Genetics;74
8.2.7;References 2;75
8.3;[3] Genetic Screens for Clock Mutants in;76
8.3.1;Abstract 3;76
8.3.2;Introduction 3;77
8.3.3;Strategies for Mutagenesis;79
8.3.4;Genetic Crosses to Generate Genotypes for a Screen;82
8.3.5;Detection of Mutant Circadian Phenotypes;88
8.3.6;Validation of Candidate Lines Identified in Genetic Screens;95
8.3.7;Concluding Comments 3;97
8.3.8;References 3;98
8.4;[4] Systems Approaches to Biological Rhythms in Drosophila;102
8.4.1;Abstract 4;102
8.4.2;Introduction 4;103
8.4.3;The Circadian Clock of the Fly: Genes and Their Products, Considered in Part from Systems Perspectives;109
8.4.4;Clock-Controlled Genes: Tentative Steps That Move the Subject from Central Pacemaking Concerns out into the System as a Whole;120
8.4.5;The Multicellular System Operating within the Brain of to Regulate Behavioral Rhythmicity;134
8.4.6;Input Systems Subserving Clock Resetting in;155
8.4.7;Actions of Rhythm-Related Genes During Drosophila Development;171
8.4.8;The Rhythm System of Drosophila as Defined Genetically Influences Weakly Appreciable Circadian Phenotypes, as Well as Noncircadian but Temporally Based Characters;184
8.4.9;The Rhythm System, as Defined Genetically, Influences Elements of Biology with No Particular Temporal Components;197
8.4.10;Conclusion 4;208
8.4.11;Acknowledgments 4;209
8.4.12;References 4;209
8.5;[5] Analysis of Circadian Rhythms in Zebrafish;227
8.5.1;Abstract 5;227
8.5.2;Introduction 5;227
8.5.3;General Methods 5;228
8.5.4;Locomotor Activity Rhythms;230
8.5.5;Bioluminescence Rhythms in;233
8.5.6;Transgenic Zebrafish;233
8.5.7;Bioluminescence Rhythms in Live Larval Zebrafish;235
8.5.8;Bioluminescence Rhythms in Cultured Organs;235
8.5.9;Recapitulating the Zebrafish Clock in Cultured Cells;236
8.5.10;Establishment of the Z3 Cell Line;236
8.5.11;Culture Conditions for Z3 Cells;237
8.5.12;Other Zebrafish-Derived Cells for Circadian Studies;238
8.5.13;Molecular Methods 5;239
8.5.14;Retroviral Infection 5;241
8.5.15;Preparation of Nuclear Extracts;243
8.5.16;References 5;244
8.6;[6] Genetic Manipulation of Circadian Rhythms in Xenopus;246
8.6.1;Abstract 6;246
8.6.2;Introduction 6;246
8.6.3;Transgenic Method;248
8.6.4;Measurement of Circadian Outputs;252
8.6.5;Concluding Remarks 6;258
8.6.6;References 6;258
8.7;[7] Forward Genetic Screens to Identify Circadian Rhythm Mutants in Mice;260
8.7.1;Abstract 7;260
8.7.2;Introduction 7;260
8.7.3;Strain Choice;261
8.7.4;ENU Safety Procedures;262
8.7.5;ENU Preparation;263
8.7.6;Injections 7;263
8.7.7;Breeding Strategies;264
8.7.8;The Efficiency of Scanning the Genome to Detect a Recessive Mutant;266
8.7.9;Production Throughput;268
8.7.10;Mutant Heritability Tests;269
8.7.11;Acknowledgments 7;270
8.7.12;References 7;270
8.8;[8] Methods to Record Circadian Rhythm Wheel Running Activity in Mice;271
8.8.1;Abstract 8;271
8.8.2;Introduction 8;271
8.8.3;Strain Choice;272
8.8.4;Facilities and Equipment Needed for a Circadian;272
8.8.5;Rhythm Screen;272
8.8.6;Experimental Design and Throughput;275
8.8.7;Data Analysis 8;278
8.8.8;Acknowledgments 8;279
8.8.9;References 8;279
8.9;[9] Genetic Approaches to Human Behavior;280
8.9.1;Abstract 9;280
8.9.2;Introduction 9;280
8.9.3;Identifying Mendelian Circadian Variants;283
8.9.4;Approaches to Complex Genetics;287
8.9.5;Challenges of Behavioral Genetics;288
8.9.6;Acknowledgments 9;290
8.9.7;References 9;290
8.10;[10] Enhanced Phenotyping of Complex Traits with a Circadian Clock Model;292
8.10.1;Abstract 10;292
8.10.2;Introduction 10;292
8.10.3;The Network Model;295
8.10.4;Clock Mutants;300
8.10.5;Conclusions 10;304
8.10.6;Acknowledgments 10;305
8.10.7;References 10;305
9;Section II: Tracking Circadian Control of Gene Activity;307
9.1;[11] Real-Time Reporting of Circadian-Regulated Gene Expression by Luciferase Imaging in Plants and Mammalian Cells;309
9.1.1;Abstract 11;309
9.1.2;Introduction 11;309
9.1.3;Plants;310
9.1.4;Mammalian Cells;312
9.1.5;Data Analysis 11;323
9.1.6;Acknowledgments 11;326
9.1.7;References 11;326
9.2;[12] Real-Time Luminescence Reporting of Circadian Gene Expression in Mammals;328
9.2.1;Abstract 12;328
9.2.2;Introduction 12;328
9.2.3;Animals and Cells;329
9.2.4;Tissue Culture;330
9.2.5;Recording Medium;332
9.2.6;Recording Apparatuses;333
9.2.7;Data Analysis 12;339
9.2.8;Conclusion 12;339
9.2.9;Acknowledgment 12;340
9.2.10;References 12;340
9.3;[13] Transgenic cAMP Response Element Reporter Flies for Monitoring Circadian Rhythms;342
9.3.1;Abstract 13;342
9.3.2;Introduction 13;342
9.3.3;Methods 13;344
9.3.4;Results 13;347
9.3.5;Discussion 13;351
9.3.6;References 13;352
9.4;[14] Analysis of Circadian Output Rhythms of Gene Expression in Neurospora and Mammalian Cells in Culture;355
9.4.1;Abstract 14;355
9.4.2;Introduction 14;355
9.4.3;DNA Microarray Analysis of Clock Control in Mammalian;367
9.4.4;Cell Culture;367
9.4.5;Concluding Remarks 14;377
9.4.6;References 14;377
9.5;[15] Molecular and Statistical Tools for Circadian Transcript Profiling;381
9.5.1;Abstract 15;381
9.5.2;Array Platforms;381
9.5.3;Experimental Design;382
9.5.4;Independent Verification of Microarray Results;389
9.5.5;Molecular Techniques;391
9.5.6;Data Analysis Techniques;394
9.5.7;Acknowledgments 15;404
9.5.8;References 15;404
9.6;[16] RNA Profiling in Circadian Biology;406
9.6.1;Abstract 16;406
9.6.2;Introduction 16;406
9.6.3;Experimental Design and Wet Work;407
9.6.4;Experimental Methodology—Dry Work;410
9.6.5;Recommendations 16;414
9.6.6;References 16;414
10;Section III: Molecular Cycles: Clock Protein Rhythms;417
10.1;[17] Analysis of Posttranslational Regulations in the Neurospora Circadian Clock;419
10.1.1;Abstract 17;419
10.1.2;Introduction 17;419
10.1.3;Posttranslational Regulations in the Neurospora Circadian Clock;420
10.1.4;Description of Methods;423
10.1.5;Concluding Remarks 17;431
10.1.6;Acknowledgments 17;431
10.1.7;References 17;431
10.2;[18] Analyzing the Degradation of PERIOD Protein by the Ubiquitin-Proteasome Pathway in Cultured Drosophila Cells;434
10.2.1;Abstract 18;434
10.2.2;Overview of Different Mechanisms Mediating the Degradation of Clock Proteins by the Ubiquitin/Proteasome Pathway;434
10.2.3;Analyzing dPER Degradation by the UPP in Cultured Drosophila Cells;437
10.2.4;Concluding Remarks 18;444
10.2.5;Acknowledgments 18;444
10.2.6;References 18;445
10.3;[19] Casein Kinase I in the Mammalian Circadian Clock;448
10.3.1;Abstract 19;448
10.3.2;Introduction 19;449
10.3.3;Bacterial Expression and Purification of an Active Form of CKI";449
10.3.4;Examination of mPER2 Stability in Tissue Culture Cells;452
10.3.5;Induce mPER2 Phosphorylation and Degradation by Phosphatase Inhibition with Calyculin A;452
10.3.6;Analyzing mPER2 Protein Degradation in Xenopus Egg Extracts;455
10.3.7;Concluding Remarks 19;457
10.3.8;References 19;457
10.4;[20] Nucleocytoplasmic Shuttling of Clock Proteins;458
10.4.1;Abstract 20;458
10.4.2;Nuclear Localization Signals in Clock Proteins;459
10.4.3;Nuclear Export Signals (NES) in Clock Proteins;464
10.4.4;Nucleocytoplasmic Shuttling of Clock Proteins;465
10.4.5;Nucleocytoplasmic Shuttling and the Heterokaryon Assay;466
10.4.6;Clock Protein Dynamics: Nucleocytoplasmic Shuttling by FLIP;468
10.4.7;Functionality of Clock Protein Shuttling;472
10.4.8;Acknowledgments 20;474
10.4.9;References 20;474
11;Section IV: Anatomical Representation of Neural Clocks;476
11.1;[21] Techniques that Revealed the Network of the Circadian Clock of Drosophila;478
11.1.1;Abstract 21;478
11.1.2;Immunocytochemistry;478
11.1.3;Reporter Gene Expression in Clock Neurons;479
11.1.4;Genetic Manipulations That Identified Clock Neurons Acting as;483
11.1.5;Circadian Pacemakers for Behavioral Rhythmicity;483
11.1.6;Ectopic Expression of Clock and Clock-Related Genes;485
11.1.7;Role of Peripheral Oscillators;486
11.1.8;Concluding Remarks 21;487
11.1.9;References 21;487
11.2;[22] The Suprachiasmatic Nucleus is a Functionally Heterogeneous Timekeeping Organ;490
11.2.1;Abstract 22;490
11.2.2;The Brain’s Clock as a Construct;490
11.2.3;In the Beginning: Anatomical Heterogeneity but Functional Homogeneity;492
11.2.4;Reducing SCN Tissue to Cells and Slices;493
11.2.5;SCN Tissue Organization and Heterogeneous Gene Expression;494
11.2.6;Dissection of the Retinorecipient Subdivision of the SCN;496
11.2.7;Heterogeneity of Phase at Tissue and Single-Cell Levels;497
11.2.8;Building a Global View: From Clock Genes to Circadian Behavior;499
11.2.9;From Center to Network;499
11.2.10;Acknowledgments 22;500
11.2.11;References 22;500
12;Section V: Mosaic Circadian Systems;505
12.1;[23] Transplantation of Mouse Embryo Fibroblasts: An Approach to Study the Physiological Pathways Linking the Suprachiasmatic Nucleus and Peripheral Clocks;507
12.1.1;Abstract 23;507
12.1.2;Signaling Pathways and Peripheral Clock;507
12.1.3;Outline of the Procedure;508
12.1.4;Preparation of Mouse Embryo Fibroblasts from Single Mouse Embryo;509
12.1.5;Preparation of Condensed MEF–Collagen Matrix;512
12.1.6;Subcutaneous Implantation Procedure;514
12.1.7;Analysis of Circadian Gene Expression by RNase Protection Assay and;515
12.1.8;Hybridization 23;515
12.1.9;References 23;515
12.2;[24] Mouse Chimeras and Their Application to Circadian Biology;516
12.2.1;Abstract 24;516
12.2.2;Introduction 24;517
12.2.3;Properties of Aggregation Chimeric Mice;518
12.2.4;A Study of Clock Chimeras Principles for Circadian Studies;519
12.2.5;Using Chimeras to Study Intercellular Interactions in Circadian Systems;520
12.2.6;General Applications for Chimeras in Circadian Studies;522
12.2.7;Technique;524
12.2.8;Summary 24;528
12.2.9;References 24;528
13;Section VI: Peripheral Circadian Clocks;531
13.1;[25] Measuring Circadian Rhythms in Olfaction Using Electroantennograms;533
13.1.1;Abstract 25;533
13.1.2;Introduction 25;533
13.1.3;Electroantennogram Apparatus Setup;535
13.1.4;Preparing to Record EAG Responses;538
13.1.5;Recording Electroantennograms;541
13.1.6;Conclusion 25;543
13.1.7;References 25;545
13.2;[26] Circadian Effects of Timed Meals (and Other Rewards);547
13.2.1;Abstract 26;547
13.2.2;Introduction 26;547
13.2.3;Entrainment of Locomotor Activity by Meal Feeding;548
13.2.4;Entrainment of Peripheral Organs by Meal Feeding;550
13.2.5;The Search for the Feeding-Entrainable Oscillator;552
13.2.6;Might Entrainment of the FEO Be Entrainment by Reward?;553
13.2.7;Are the FEO and Methamphetamine-Inducible Oscillator the Same Clock?;555
13.2.8;Is It ‘‘Reward’’ After All?;556
13.2.9;Acknowledgments 26;557
13.2.10;References 26;557
13.3;[27] Peripheral Clocks and the Regulation of Cardiovascular and Metabolic Function;562
13.3.1;Abstract 27;562
13.3.2;The Emerging Importance of Peripheral Clocks;562
13.3.3;NPAS2 and Other Candidate Members of the Core Clock in the Periphery;563
13.3.4;ChIP Analysis of Promoter Occupancy;564
13.3.5;Analysis of Circadian Rhythms by Serum Shock Analysis;565
13.3.6;Zeitgeber, Circadian Time, and Constant Darkness: Lights on, Lights off ?;566
13.3.7;Isolation of RNA from Murine Aorta;567
13.3.8;Circadian Variation in Metabolism and Diabetes;569
13.3.9;Adapting Metabolic Assays to Assess Circadian Variations in Mice;569
13.3.10;Blood Pressure Studies;572
13.3.11;Circadian Profiles in Cardiovascular Physiology and Disease;572
13.3.12;Conclusion 27;574
13.3.13;References 27;574
14;Section VII: Cell and Tissue Culture System;578
14.1;[28] Circadian Gene Expression in Cultured Cells;580
14.1.1;Abstract 28;580
14.1.2;Introduction 28;580
14.1.3;Monitoring Circadian Gene Expression in Cultured Cells;583
14.1.4;Choice of Cell Line;590
14.1.5;Conclusions and Perspectives 28;591
14.1.6;Acknowledgments 28;592
14.1.7;References 28;592
14.2;[29] Cell Culture Models for Oscillator and Pacemaker Function: Recipes for Dishes with Circadian Clocks?;595
14.2.1;Abstract 29;595
14.2.2;Biological Clocks in Vertebrates;595
14.2.3;Molecular Clockworks;597
14.2.4;Avian Pineal Gland;598
14.2.5;Methods in Pinealocyte Culture;599
14.2.6;Mammalian Suprachiasmatic Nucleus and Primary Cell Culture;602
14.2.7;Immortalized SCN2.2 Cell Line;603
14.2.8;Shocked Fibroblast Model;610
14.2.9;Relative Merits of Different Cell Culture Approaches;611
14.2.10;Acknowledgments 29;612
14.2.11;References 29;612
14.3;[30] Analysis of Circadian Mechanisms in the Suprachiasmatic Nucleus by Transgenesis and Biolistic Transfection;616
14.3.1;Abstract 30;616
14.3.2;Organotypic Slices of Suprachiasmatic Nuclei;617
14.3.3;Dissection Medium;618
14.3.4;Culture Medium;618
14.3.5;Real-Time Recording of Circadian Activity in Organotypic SCN Slice;619
14.3.6;Recording Medium;621
14.3.7;Fluorescent Imaging of Circadian Gene Expression in the SCN Organotypical Slice;622
14.3.8;Biolistic Transfection of SCN Organotypical Slices;623
14.3.9;Imaging Circadian Gene Expression Using Biolistically Transfected Reporter Genes;627
14.3.10;Acknowledgments 30;628
14.3.11;References 30;628
14.4;[31] Oligodeoxynucleotide Methods for Analyzing the Circadian Clock in the Suprachiasmatic Nucleus;630
14.4.1;Abstract 31;630
14.4.2;Introduction 31;630
14.4.3;Analysis of SCN Rhythmicity In Vivo and In Vitro;631
14.4.4;Targeted Deletion of Clock Genes;633
14.4.5;Antisense Oligodeoxynucleotides and Small Interfering RNA as Tools to Investigate Gene Function in Circadian Timekeeping;635
14.4.6;Decoy Oligodeoxynucleotides as Tools to Investigate Transcriptional Control in Circadian Timekeeping;638
14.4.7;Conclusions 31;641
14.4.8;Acknowledgments 31;641
14.4.9;References 31;642
14.5;[32] Assaying the Drosophila Negative Feedback Loop with RNA Interference in S2 Cells;647
14.5.1;Abstract 32;647
14.5.2;Introduction 32;647
14.5.3;Methodology 32;650
14.5.4;Transient Transfection;652
14.5.5;Generating Stable Cell Lines;655
14.5.6;References 32;658
14.6;[33] Role of Neuronal Membrane Events in Circadian Rhythm Generation;660
14.6.1;Abstract 33;660
14.6.2;Introduction 33;660
14.6.3;Input Pathways and Entrainment;661
14.6.4;Role of Transmembrane Ionic Fluxes in Rhythm Generation;666
14.6.5;Output and Rhythm Expression;670
14.6.6;Concluding Remarks 33;673
14.6.7;References 33;673
15;Section VIII: Intercellular Signaling;680
15.1;[34] A Screen for Secreted Factors of the Suprachiasmatic Nucleus;682
15.1.1;Abstract 34;682
15.1.2;Introduction 34;682
15.1.3;General Strategy;683
15.1.4;Signal Sequence Trap;684
15.1.5;Behavioral Screen for a Possible Role of SCN Factors in Regulating Locomotor Activity;693
15.1.6;Acknowledgments 34;698
15.1.7;References 34;699
15.2;[35] Genetic and Biochemical Strategies for Circadian Control;700
15.2.1;Abstract 35;700
15.2.2;Introduction 35;700
15.2.3;Genetic Approaches to Studying Clock Control Elements;701
15.2.4;Biochemical Strategies for Identifying mRNA Targets of Clock-Regulated RNA-Binding Proteins;711
15.2.5;Appendix 35;715
15.2.6;Acknowledgments 35;716
15.2.7;References 35;716
15.3;[36] Membranes, Ions, and Clocks: Testing the Njus-Sulzman-Hastings Model of the Circadian Oscillator;719
15.3.1;Abstract 36;719
15.3.2;Membrane Model for the Circadian Clock;720
15.3.3;Testing the Membrane Model in the Molluscan Eye;720
15.3.4;Testing the Membrane Model in the Mammalian Suprachiasmatic Nucleus;721
15.3.5;Testing the Membrane Model in Drosphila melanogaster;724
15.3.6;Detailed Procedure for Electrical Silencing of Drosophila Pacemaker Neurons with a dORK(delta) Potassium Channel;726
15.3.7;Conclusions 36;727
15.3.8;Acknowledgments 36;727
15.3.9;References 36;728
16;Section IX: Photoresponsive Clocks;731
16.1;[37] Mammalian Photoentrainment: Results, Methods, and Approaches;733
16.1.1;Abstract 37;733
16.1.2;Introduction 37;733
16.1.3;Investigating Photopigments;740
16.1.4;Methods for Action Spectroscopy;742
16.1.5;Phase Shifting in the rd/ rd cl Mouse;752
16.1.6;Conclusions 37;757
16.1.7;References 37;758
16.2;[38] Cryptochromes and Circadian Photoreception in Animals;762
16.2.1;Abstract 38;762
16.2.2;Introduction 38;762
16.2.3;Mammalian Cryptochromes;765
16.2.4;Zebrafish Cryptochromes;774
16.2.5;Cryptochrome;778
16.2.6;Conclusions 38;778
16.2.7;Acknowledgments 38;779
16.2.8;References 38;779
16.3;[39] Nonvisual Ocular Photoreception in the Mammal;782
16.3.1;Abstract 39;782
16.3.2;Historical Introduction;782
16.3.3;The Melanopsin Hypothesis;783
16.3.4;The Cryptochrome Hypothesis;785
16.3.5;References 39;789
17;Section X: Sleeping Flies;792
17.1;[40] Essentials of Sleep Recordings in Moving Beyond Sleep Time;794
17.1.1;Abstract 40;794
17.1.2;Introduction 40;794
17.1.3;Procedure;795
17.1.4;Constraints;796
17.1.5;Basic Characteristics of Sleep;799
17.1.6;Sleep Deprivation;803
17.1.7;Sexual Dimorphism;805
17.1.8;Conclusions 40;805
17.1.9;Acknowledgment 40;806
17.1.10;References 40;806
17.2;[41] Drosophila melanogaster: An Insect Model for Fundamental Studies of Sleep;807
17.2.1;Abstract 41;807
17.2.2;Introduction 41;807
17.2.3;Baseline Sleep: Locomotor Assay and Videography;809
17.2.4;Sleep Deprivation and Rebound;811
17.2.5;Arousal Threshold;813
17.2.6;Sleep Intensity;814
17.2.7;Pharmacological Studies;815
17.2.8;Electrophysiology Studies;816
17.2.9;Sleep-Relevant Genes;817
17.2.10;Shortcomings and Future Prospects;822
17.2.11;Acknowledgments 41;824
17.2.12;References 41;824
18;Section XI: Circadian Biology of Populations;829
18.1;[42] Molecular Evolution and Population Genetics of Circadian Clock Genes;831
18.1.1;Abstract 42;831
18.1.2;Introduction 42;831
18.1.3;Phylogenetic Analysis;832
18.1.4;Neutrality Tests;837
18.1.5;Polymorphism in Human Clock Genes;842
18.1.6;Quantitative Trait Loci Analysis;842
18.1.7;Statistical Resampling Methods in Molecular Evolution;843
18.1.8;Interspecific Transformations;844
18.1.9;Protein Alignments and Predictions;845
18.1.10;Conclusions 42;846
18.1.11;Computer Program for Phylogeny and Molecular Evolution;846
18.1.12;Acknowledgments 42;847
18.1.13;References 42;847
18.2;[43] Testing the Adaptive Value of Circadian Systems;852
18.2.1;Abstract 43;852
18.2.2;Background 43;852
18.2.3;Adaptive Significance of Clocks;855
18.2.4;Tests of Adaptive Significance;858
18.2.5;Natural Selection and the Evolution of Clocks: ‘‘Escape from Light?’’;865
18.2.6;For Future Studies;867
18.2.7;Acknowledgments 43;869
18.2.8;References 43;869
19;Section XII: Circadian Clocks Affecting Noncircadian Biology;872
19.1;[44] A ‘‘Bottom-Counting’’ Video System for Measuring Cocaine-Induced Behaviors in;874
19.1.1;Abstract 44;874
19.1.2;Introduction 44;874
19.1.3;Behavioral Scoring;875
19.1.4;Bottom-Counting Assay;876
19.1.5;Automated Carousel and Image Capture;880
19.1.6;Proof of Principle;881
19.1.7;References 44;884
19.2;[45] The Circadian Clock and Tumor Suppression by Mammalian Period Genes;885
19.2.1;Abstract 45;885
19.2.2;Introduction 45;885
19.2.3;Genetic Studies Demonstrated that mPER1 and mPER2 are Circadian Regulators;886
19.2.4;Noncircadian Phenotypes of mPer1 and mPer2 Mutant Mice;888
19.2.5;Tumor Suppression Function of mPER2;889
19.2.6;Circadian Clock Regulates Cell Cycle Genes;890
19.2.7;New Links Between Growth Regulators and Circadian Clock;892
19.2.8;Acknowledgments 45;893
19.2.9;References 45;893
20;back matter;895
21;Author Index;895
22;Index;936



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