InhaltsangabeList of Contributors xiii Preface xvii Part I Fundamental Concepts 1 1 Cytosolic and Transcriptional Cycles Underlying Circadian Oscillations 3 Michael H. Hastings and John S. O'Neill 1.1 Introduction 3 1.2 Assembling the transcriptional feedback loop 5 1.3 Keeping the transcriptional clockworks in tune 9 1.4 Building posttranslational mechanisms into the circadian pacemaker 13 1.5 Is the transcriptional clock paramount? 15 1.6 Conclusion: cytoscillators, clocks and therapies 18 References 18 2 Molecular Determinants of Human Circadian Clocks 25 Steven A. Brown 2.1 Molecular elements of human clocks: a brief review 25 2.2 Peripheral and central clocks 26 2.3 Signaling to peripheral circadian clocks 28 2.4 Human peripheral and central clocks 29 2.5 Human genetics 29 2.6 Technologies for measurement of human circadian clocks 30 2.7 Cellular methods 30 2.8 Omics?]based methods to analyze human clocks 32 2.9 Summary and outlook 33 References 33 3 The Suprachiasmatic Nucleus (SCN): Critical Points 37 Christopher S. Colwell, Paul Witkovsky, and Rae Silver 3.1 SCN is site of master circadian pacemaker in mammals 37 3.2 SCN receives photic information through a specialized light detection pathway 39 3.3 SCN neurons are endogenous single cell oscillators that generate rhythms in neural activity 40 3.4 The SCN has circuit level organization that is just beginning to be unraveled 42 3.5 Coupling with the SCN circuit is mediated by a set of peptides with VIP on top of the hierarchy 44 3.6 SCN outputs 44 3.7 SCN in aging and disease 50 References 51 4 Sleep and Circadian Rhythms: Reciprocal Partners in the Regulation of Physiology and Behavior 57 Ralph Mistlberger 4.1 Introduction 57 4.2 What is sleep 59 4.3 Circadian regulation of sleep 60 4.4 Reciprocity: sleep-wake feedback to the circadian clock 69 4.5 Conclusions: Circadian clocks and sleep are intertwined processes 73 References 73 5 Circadian Regulation of Arousal and its Role in Fatigue 81 David R. Bonsall and Mary E. Harrington 5.1 Defining arousal 81 5.2 Brain structures important for arousal 83 5.3 Neurochemicals signaling the states of arousal 84 5.4 Circadian regulation of the arousal system 86 5.5 Influence of input pathways on circadian regulation of arousal 88 5.6 Sustained states of fatigue: a disorder of the arousal network? 88 5.7 Conclusions 90 References 91 Part II Circadian Regulation of Major Physiological Systems 95 6 Physiology of the Adrenal and Liver Circadian Clocks 97 Alexei Leliavski and Henrik Oster 6.1 Introduction 97 6.2 Circadian control of adrenal function 98 6.3 Circadian control of liver function 101 6.4 Conclusion 105 References 105 7 Nutrition and Diet as Potent Regulators of the Liver Clock 107 Yu Tahara and Shigenobu Shibata 7.1 Introduction 107 7.2 Food is a "zeitgeber": The FEO in the brain 107 7.3 The FEO in peripheral tissues 109 7.4 What should we eat? What types of food can stimulate the peripheral clock? 110 7.5 When should we eat? Application to human life science 112 7.6 Circadian rhythm and obesity and diabetes 113 References 116 8 The Cardiovascular Clock 119 R. Daniel Rudic 8.1 Introduction 119 8.2 The vascular clock 119 8.3 Circadian clock regulation of the endothelial cell layer of blood vessels 120 8.4 The circadian clock in vascular disease 121 8.5 The circadian clock and vascular cell signaling 122 8.6 The circadian rhythm in blood pressure, nighttime hypertension, and cardiovascular disease in humans 123 8.7 Diabetes, obesity, and blood pressure 125 8.8 AT influences the circadian rhythm in experimental hypertension 126 8.9 The circadian clock and fluid balance 127 8.10 The circadian clock and peripheral vascular resistance 127 8.11 Conclusion 130 References 130 9 Hypertension Caused by Disruption of

Christopher S. Colwell is a neuroscientist and Professor in the Department of Psychiatriary and Biobehavioral Sciences at the University of California, Los Angeles.

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