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עמודים / Pages | 880 |
---|---|
פורמט | Paperback / softback |
ISBN10 | 1119454174 |
יצא לאור ב | New York |
תאריך יציאה לאור | 2 בפבר׳ 2018 |
תוכן עניינים | 1 Introduction to Cell Biology 1 1.1 The Discovery of Cells 2 Microscopy 2 Cell Theory 3 1.2 Basic Properties of Cells 3 Cells are Highly Complex and Organized 3 Cells Possess a Genetic Program and the Means to Use It 5 Cells Are Capable of Producing More of Themselves 5 Cells Acquire and Utilize Energy 5 Cells Carry Out a Variety of Chemical Reactions 6 Cells Engage in Mechanical Activities 6 Cells are Able to Respond to Stimuli 6 Cells Are Capable of Self-Regulation 6 Cells Evolve 7 1.3 Two Fundamentally Different Classes of Cells 8 1.4 Types of Prokaryotic Cells 14 Domain Archaea and Domain Bacteria 14 Prokaryotic Diversity 14 1.5 Types of Eukaryotic Cells 15 Cell Differentiation 16 Model Organisms 16 1.6 The Sizes of Cells and Their Components 18 1.7 Viruses 19 Viroids 22 THE HUMAN PERSPECTIVE 23 The Prospect of Cell Replacement Therapy 23 EXPERIMENTAL PATHWAYS 27 The Origin of Eukaryotic Cells 27 2 The Structure and Functions of Biological Molecules 33 2.1 Covalent Bonds 34 Polar and Nonpolar Molecules 35 Ionization 36 2.2 Noncovalent Bonds 36 Ionic Bonds: Attractions between Charged Atoms 36 Hydrogen Bonds 36 Hydrophobic Interactions and van der Waals Forces 37 The Life-Supporting Properties of Water 38 2.3 Acids, Bases, and Buffers 39 2.4 The Nature of Biological Molecules 40 Functional Groups 41 A Classification of Biological Molecules by Function 41 2.5 Carbohydrates 42 The Structure of Simple Sugars 43 Stereoisomerism 43 Linking Sugars Together 44 Polysaccharides 45 2.6 Lipids 47 Fats 47 Steroids 48 Phospholipids 48 2.7 Building Blocks of Proteins 49 The Structures of Amino Acids 50 The Properties of the Side Chains 51 2.8 Primary and Secondary Structures of Proteins 54 Primary Structure 54 Secondary Structure 55 2.9 Tertiary Structure of Proteins 56 Myoglobin: The First Globular Protein Whose Tertiary Structure Was Determined 57 Tertiary Structure May Reveal Unexpected Similarities between Proteins 58 Protein Domains 58 Dynamic Changes within Proteins 59 2.10 Quaternary Structure of Proteins 60 The Structure of Hemoglobin 60 Protein-Protein Interactions 61 2.11 Protein Folding 61 Dynamics of Protein Folding 62 The Role of Molecular Chaperones 63 2.12 Proteomics and Interactomics 64 Proteomics 64 Interactomics 66 2.13 Protein Engineering 67 Production of Novel Proteins 67 Structure-Based Drug Design 68 2.14 Protein Adaptation and Evolution 69 2.15 Nucleic Acids 71 2.16 The Formation of Complex Macromolecular Structures 72 The Assembly of Tobacco Mosaic Virus Particles 73 The Assembly of Ribosomal Subunits 73 THE HUMAN PERSPECTIVE 73 I. Do Free Radicals Cause Aging? 73 II. Protein Misfolding Can Have Deadly Consequences 74 EXPERIMENTAL PATHWAYS 79 Chaperones-Helping Proteins Reach Their Proper Folded State 79 3 Bioenergetics, Enzymes, and Metabolism 87 3.1 Bioenergetics 88 The First Law of Thermodynamics 88 The Second Law of Thermodynamics 89 3.2 Free Energy 90 Free?Energy Changes in Chemical Reactions 91 Free?Energy Changes in Metabolic Reactions 92 3.3 Coupling Endergonic and Exergonic Reactions 94 3.4 Equilibrium versus Steady?State Metabolism 94 3.5 Enzymes as Biological Catalysts 95 The Properties of Enzymes 96 Overcoming the Activation Energy Barrier 96 The Active Site 98 3.6 Mechanisms of Enzyme Catalysis 99 Substrate Orientation 100 Changing Substrate Reactivity 100 Inducing Strain in the Substrate 100 3.7 Enzyme Kinetics 103 The Michaelis?Menten Model of Enzyme Kinetics 103 Enzyme Inhibitors 105 3.8 Metabolism 106 Oxidation and Reduction: A Matter of Electrons 107 The Capture and Utilization of Energy 108 3.9 Glycolysis and ATP Production 108 ATP Production in Glycolysis 109 Anaerobic Oxidation of Pyruvate: The Process of Fermentation 111 3.10 Reducing Power 112 3.11 Metabolic Regulation 113 Altering Enzyme Activity by Covalent Modification 113 Altering Enzyme Activity by Allosteric Modulation 113 3.12 Separating Catabolic and Anabolic Pathways 114 THE HUMAN PERSPECTIVE 115 I. The Growing Problem of Antibiotic Resistance 115 II. Caloric Restriction and Longevity 118 4 Genes, Chromosomes, and Genomes 123 4.1 The Concept of a Gene as a Unit of Inheritance 124 4.2 The Discovery of Chromosomes 125 4.3 Chromosomes: The Physical Carriers of the Genes 126 The Chromosome as a Linkage Group 127 4.4 Genetic Analysis in Drosophila 127 Crossing Over and Recombination 128 Mutagenesis and Giant Chromosomes 129 4.5 The Structure of DNA 129 The Watson?Crick Proposal 132 The Importance of the Watson?Crick Proposal 132 4.6 DNA Supercoiling 134 4.7 The Structure of the Genome 136 DNA Denaturation 137 DNA Renaturation 137 4.8 The Stability of the Genome 141 Whole?Genome Duplication (Polyploidization) 141 Duplication and Modification of DNA Sequences 141 Evolution of Globin Genes 142 4.9 "Jumping Genes" and the Dynamic Nature of the Genome 143 Transposons 144 The Role of Mobile Genetic Elements in Genome Evolution 144 4.10 Sequencing Genomes: The Footprints of Biological Evolution 146 4.11 Comparative Genomics: "If It's Conserved, It Must Be Important" 148 4.12 The Genetic Basis of "Being Human" 148 4.13 Genetic Variation within the Human Species Population 150 DNA Sequence Variation 150 Structural Variation 151 Copy Number Variation 152 THE HUMAN PERSPECTIVE 152 I. Diseases That Result from Expansion of Trinucleotide Repeats 152 II. Application of Genomic Analyses to Medicine 154 EXPERIMENTAL PATHWAYS 157 The Chemical Nature of the Gene 157 5 The Path to Gene Expression 165 5.1 The Relationship between Genes, Proteins, and RNAs 166 Evidence That DNA Is the Genetic Material 166 An Overview of the Flow of Information through the Cell 167 5.2 The Role of RNA Polymerases in Transcription 169 5.3 An Overview of Transcription in Both Prokaryotic and Eukaryotic Cells 171 Transcription in Bacteria 171 Transcription and RNA Processing in Eukaryotic Cells 172 5.4 Synthesis and Processing of Eukaryotic Ribosomal and Transfer RNAs 174 Synthesis and Processing of the rRNA Precursor 174 The Role of snoRNAs in the Processing of Pre?rRNA 176 Synthesis and Processing of the 5S rRNA 176 Transfer RNAs 177 5.5 Synthesis and Structure of Eukaryotic Messenger RNAs 178 The Formation of Heterogeneous Nuclear RNA (hnRNA) 178 The Machinery for mRNA Transcription 178 The Structure of mRNAs 181 5.6 Split Genes: An Unexpected Finding 181 5.7 The Processing of Eukaryotic Messenger RNAs 184 5' Caps and 3' Poly(A) Tails 185 RNA Splicing: Removal of Introns from a Pre?RNA 186 5.8 Evolutionary Implications of Split Genes and RNA Splicing 189 5.9 Creating New Ribozymes in the Laboratory 191 5.10 Small Regulatory RNAs and RNA Silencing Pathway 191 5.11 Small RNAs: miRNAs and piRNAs 193 miRNAs: A Class of Small RNAs that Regulate Gene Expression 193 piRNAs: A Class of Small RNAs that Function in Germ Cells 194 5.12 CRISPR and other Noncoding RNAs 195 CRISPR: Noncoding RNA in Bacteria 195 Other Noncoding RNAs 195 5.13 Encoding Genetic Information 196 The Properties of the Genetic Code 196 Identifying the Codons 197 5.14 Decoding the Codons: The Role of Transfer RNAs 198 The Structure of tRNAs 198 tRNA Charging 200 5.15 Translating Genetic Information: Initiation 201 Initiation of Translation in Prokaryotes 202 Initiation of Translation in Eukaryotes 203 The Role of the Ribosome 203 5.16 Translating Genetic Information: Elongation and Termination 205 Elongation Step 1: Aminoacyl?tRNA Selection 205 Elongation Step 2: Peptide Bond Formation 205 Elongation Step 3: Translocation 205 Elongation Step 4: Releasing the Deacylated tRNA 206 Termination 207 5.17 mRNA Surveillance and Quality Control 208 5.18 Polyribosomes 209 THE HUMAN PERSPECTIVE 210 Clinical Applications of RNA Interference 210 EXPERIMENTAL PATHWAYS 212 The Role of RNA as a Catalyst 212 6 Controlling Gene Expression 220 6.1 Control of Gene Expression in Bacteria 221 Organization of Bacterial Genomes 221 The Bacterial Operon 221 Riboswitches 224 6.2 Control of Gene Expression in Eukaryotes: Structure and Function of the Cell Nucleus 225 The Nuclear Pore Complex and Its Role in Nucleocytoplasmic Trafficking 227 RNA Transport 230 6.3 Chromosomes and Chromatin 230 Nucleosomes: The Lowest Level of Chromosome Organization 230 Higher Levels of Chromatin Structure 232 6.4 Heterochromatin and Euchromatin 234 X Chromosome Inactivation 234 The Histone Code and Formation of Heterochromatin 235 6.5 The Structure of a Mitotic Chromosome 238 Telomeres 240 Centromeres 243 6.6 Epigenetics: There's More to Inheritance than DNA 243 6.7 The Nucleus as an Organized Organelle 244 6.8 An Overview of Gene Regulation in Eukaryotes 247 6.9 Transcriptional Control 248 DNA Microarrays 249 RNA Sequencing 251 6.10 The Role of Transcription Factors in Regulating Gene Expression 252 The Role of Transcription Factors in Determining a Cell's Phenotype 252 6.11 The Structure of Transcription Factors 253 Transcription Factor Motifs 253 6.12 DNA Sites Involved in Regulating Transcription 256 6.13 The Glucocorticoid Receptor: An Example of Transcriptional Activation 258 6.14 Transcriptional Activation: The Role of Enhancers, Promoters, and Coactivators 259 Coactivators That Interact with the Basal Transcription Machinery 260 Coactivators That Alter Chromatin Structure 260 6.15 Transcriptional Activation from Paused Polymerases 263 6.16 Transcriptional Repression 264 DNA Methylation 264 Genomic Imprinting 265 Long Noncoding RNAs (lncRNAs) as Transcriptional Repressors 266 6.17 RNA Processing Control 267 6.18 Translational Control 269 Initiation of Translation 269 Cytoplasmic Localization of mRNAs 270 The Control of mRNA Stability 271 6.19 The Role of MicroRNAs in Translational Control 273 6.20 Posttranslational Control: Determining Protein Stability 274 THE HUMAN PERSPECTIVE 275 Chromosomal Aberrations and Human Disorders 275 7 DNA Replication and Repair 282 7.1 DNA Replication 283 7.2 DNA Replication in Bacterial Cells 286 Replication Forks and Bidirectional Replication 287 Unwinding the Duplex and Separating the Strands 287 The Properties of DNA Polymerases 288 Semidiscontinuous Replication 289 7.3 The Machinery Operating at the Replication Fork 291 7.4 The Structure and Functions of DNA Polymerases 293 Exonuclease Activities of DNA Polymerases 293 Ensuring High Fidelity during DNA Replication 294 7.5 Replication in Viruses 296 7.6 DNA Replication in Eukaryotic Cells 296 Initiation of Replication in Eukaryotic Cells 297 Restricting Replication to Once Per Cell Cycle 297 The Eukaryotic Replication Fork 298 Replication and Nuclear Structure 300 7.7 Chromatin Structure and Replication 300 7.8 DNA Repair 302 Nucleotide Excision Repair 302 Base Excision Repair 303 Mismatch Repair 304 Double?Strand Breakage Repair 304 7.9 Between Replication and Repair 305 THE HUMAN PERSPECTIVE 306 Consequences of DNA Repair Deficiencies 306 8 Cellular Membrane 311 8.1 Introduction to the Plasma Membrane 312 An Overview of Membrane Functions 312 A Brief History of Studies on Plasma Membrane Structure 313 8.2 The Chemical Composition of Membranes 315 Membrane Lipids 316 The Nature and Importance of the Lipid Bilayer 317 The Asymmetry of Membrane Lipids 319 8.3 Membrane Carbohydrates 319 8.4 The Structure and Functions of Membrane Proteins 320 Integral Membrane Proteins 321 Peripheral Membrane Proteins 322 Lipid?Anchored Membrane Proteins 322 8.5 Studying the Structure and Properties of Integral Membrane Proteins 323 Identifying Transmembrane Domains 324 Experimental Approaches to Identifying Conformational Changes within an Integral Membrane Protein 325 8.6 Membrane Lipids and Membrane Fluidity 327 The Importance of Membrane Fluidity 328 Maintaining Membrane Fluidity 328 Lipid Rafts 329 8.7 The Dynamic Nature of the Plasma Membrane 329 The Diffusion of Membrane Proteins after Cell Fusion 330 Restrictions on Protein and Lipid Mobility 331 8.8 The Red Blood Cell: An Example of Plasma Membrane Structure 334 Integral Proteins of the Erythrocyte Membrane 334 The Erythrocyte Membrane Skeleton 336 8.9 The Movement of Substances across Cell Membranes 336 The Energetics of Solute Movement 336 Formation of an Electrochemical Gradient 337 8.10 Diffusion through the Lipid Bilayer 338 Diffusion of Substances through Membranes 338 The Diffusion of Water through Membranes 338 8.11 The Diffusion of Ions through Membranes 340 8.12 Facilitated Diffusion 345 8.13 Active Transport 346 Primary Active Transport: Coupling Transport to ATP Hydrolysis 346 Other Primary Ion Transport Systems 347 Using Light Energy to Actively Transport Ions 348 Secondary Active Transport (or Cotransport): Coupling Transport to Existing Ion Gradients 348 8.14 Membrane Potentials 350 The Resting Potential 350 The Action Potential 352 8.15 Propagation of Action Potentials as an Impulse 353 8.16 Neurotransmission: Jumping the Synaptic Cleft 354 Actions of Drugs on Synapses 356 Synaptic Plasticity 357 THE HUMAN PERSPECTIVE 357 Defects in Ion Channels and Transporters as a Cause of Inherited Disease 357 EXPERIMENTAL PATHWAYS 359 The Acetylcholine Receptor 359 9 Mitochondrion and Aerobic Respiration 368 9.1 Mitochondrial Structure and Function 369 Mitochondrial Membranes 370 The Mitochondrial Matrix 372 9.2 Oxidative Metabolism in the Mitochondrion 372 The Tricarboxylic Acid (TCA) Cycle 373 The Importance of Reduced Coenzymes in the Formation of ATP 375 9.3 The Role of Mitochondria in the Formation of ATP 377 Oxidation-Reduction Potentials 377 Electron Transport 379 Types of Electron Carriers 379 9.4 Electron?Transport Complexes 381 Complex I (NADH dehydrogenase) 383 Complex II (succinate dehydrogenase) 384 Complex III (cytochrome bc1) 384 Complex IV (cytochrome c oxidase) 384 9.5 Translocation of Protons and the Establishment of a Proton? Motive Force 385 9.6 The Machinery for ATP Formation 386 The Structure of ATP Synthase 387 9.7 The Binding Change Mechanism of ATP Formation 388 Components of the Binding Change Hypothesis 388 Evidence to Support the Binding Change Mechanism and Rotary Catalysis 389 9.8 Using the Proton Gradient 391 The Role of the Fo Portion of ATP Synthase in ATP Synthesis 391 Other Roles for the Proton?Motive Force in Addition to ATP Synthesis 392 9.9 Peroxisomes 392 THE HUMAN PERSPECTIVE 394 I. The Role of Anaerobic and Aerobic Metabolism in Exercise 394 II. Diseases that Result from Abnormal Mitochondrial or Peroxisomal Function 395 10 Chloroplast and Photosynthesis 401 10.1 The Origin of Photosynthesis 402 10.2 Chloroplast Structure and Function 403 10.3 An Overview of Photosynthetic Metabolism 404 10.4 The Absorption of Light 405 Photosynthetic Pigments 406 10.5 Photosynthetic Units and Reaction Centers 407 Oxygen Formation: Coordinating the Action of Two Different Photosynthetic Systems 408 10.6 The Operations of Photosystem II and Photosystem I 409 PSII Operations: Obtaining Electrons by Splitting Water 409 PSI Operations: The Production of NADPH 412 10.7 An Overview of Photosynthetic Electron Transport 413 Killing Weeds by Inhibiting Electron Transport 414 10.8 Photophosphorylation 415 Noncyclic Versus Cyclic Photophosphorylation 415 10.9 Carbon Dioxide Fixation and the Carbohydrate Synthesis 415 Carbohydrate Synthesis in C3 Plants 416 Redox Control 416 Photorespiration 417 Peroxisomes and Photorespiration 418 10.10 Carbohydrate Synthesis in C4 and CAM Plants 420 THE HUMAN PERSPECTIVE 421 Global Warming and Carbon Sequestration 421 11 The Extracellular Matrix and Cell Interactions 426 11.1 Overview of Extracellular Interactions 427 11.2 The Extracellular Space 428 The Extracellular Matrix 428 11.3 Components of the Extracellular Matrix 430 Collagen 430 Proteoglycans 432 Fibronectin 433 Laminin 433 11.4 Dynamic Properties of the Extracellular Matrix 435 11.5 Interactions of Cells with Extracellular Materials 436 Integrins 436 11.6 Anchoring Cells to Their Substratum 438 Focal Adhesions 438 Hemidesmosomes 440 11.7 Interactions of Cells with Other Cells 441 Selectins 441 The Immunoglobulin Superfamily 442 Cadherins 443 11.8 Adherens Junctions and Desmosomes: Anchoring Cells to Other Cells 445 11.9 The Role of Cell?Adhesion Receptors in Transmembrane Signaling 447 11.10 Tight Junctions: Sealing the Extracellular Space 447 11.11 Gap Junctions and Plasmodesmata: Mediating Intercellular Communication 449 Gap Junctions 449 Plasmodesmata 451 11.12 Cell Walls 453 THE HUMAN PERSPECTIVE 455 The Role of Cell Adhesion in Inflammation and Metastasis 455 EXPERIMENTAL PATHWAYS 457 The Role of Gap Junctions in Intercellular Communication 457 12 Cellular Organelles and Membrane Trafficking 463 12.1 An Overview of the Endomembrane System 464 12.2 A Few Approaches to the Study of Endomembranes 466 Insights Gained from Autoradiography 466 Insights Gained from the Use of the Green Fluorescent Protein 467 Insights Gained from the Analysis of Subcellular Fractions 468 Insights Gained from the Use of Cell?Free Systems 469 Insights Gained from the Study of Mutant Phenotypes 470 12.3 The Endoplasmic Reticulum 472 The Smooth Endoplasmic Reticulum 473 The Rough Endoplasmic Reticulum 473 12.4 Functions of the Rough Endoplasmic Reticulum 473 Synthesis of Proteins on Membrane?Bound versus Free Ribosomes 473 Synthesis of Secretory, Lysosomal, or Plant Vacuolar Proteins 475 Processing of Newly Synthesized Proteins in the Endoplasmic Reticulum 476 Synthesis of Integral Membrane Proteins on ER?Bound Ribosomes 476 12.5 Membrane Biosynthesis in the Endoplasmic Reticulum 477 12.6 Glycosylation in the Rough Endoplasmic Reticulum 479 12.7 Mechanisms That Ensure the Destruction of Misfolded Proteins 481 12.8 ER to Golgi Vesicular Transport 482 12.9 The Golgi Complex 482 Glycosylation in the Golgi Complex 484 The Movement of Materials through the Golgi Complex 485 12.10 Types of Vesicle Transport and Their Functions 487 COPII?Coated Vesicles: Transporting Cargo from the ER to the Golgi Complex 488 COPI?Coated Vesicles: Transporting Escaped Proteins Back to the ER 489 12.11 Beyond the Golgi Complex: Sorting Proteins at the TGN 491 Sorting and Transport of Lysosomal Enzymes 491 Sorting and Transport of Nonlysosomal Proteins 493 12.12 Targeting Vesicles to a Particular Compartment 493 12.13 Exocytosis 496 12.14 Lysosomes 496 12.15 Plant Cell Vacuoles 498 12.16 Endocytosis 498 Receptor?Mediated Endocytosis and the Role of Coated Pits 499 The Role of Phosphoinositides in the Regulation of Coated Vesicles 501 12.17 The Endocytic Pathway 502 12.18 Phagocytosis 505 12.19 Posttranslational Uptake of Proteins by Peroxisomes, Mitochondria, and Chloroplasts 505 Uptake of Proteins into Peroxisomes 506 Uptake of Proteins into Mitochondria 506 Uptake of Proteins into Chloroplasts 507 THE HUMAN PERSPECTIVE 508 Disorders Resulting from Defects in Lysosomal Function 508 EXPERIMENTAL PATHWAYS 510 Receptor?Mediated Endocytosis 510 13 The Cytoskeleton 517 13.1 Overview of the Major Functions of the Cytoskeleton 518 13.2 Microtubules: Structure and Function 520 Structure and Composition of Microtubules 520 Microtubule?Associated Proteins 521 Microtubules as Structural Supports and Organizers 521 Microtubules as Agents of Intracellular Motility 522 13.3 Motor Proteins: Kinesins and Dyneins 524 Motor Proteins Traverse the Microtubular Cytoskeleton 524 Kinesins 524 Cytoplasmic Dynein 526 13.4 Microtubule?Organizing Centers (MTOCs) 527 Centrosomes 528 Basal Bodies and Other MTOCs 530 Microtubule Nucleation 530 13.5 Microtubule Dynamics 530 The Dynamic Properties of Microtubules 530 The Underlying Basis of Microtubule Dynamics 532 13.6 Cilia and Flagella: Structure and Function 534 Structure of Cilia and Flagella 535 Growth by Intraflagellar Transport 537 The Mechanism of Ciliary and Flagellar Locomotion 539 13.7 Intermediate Filaments 541 Intermediate Filament Assembly and Disassembly 541 Types and Functions of Intermediate Filaments 543 13.8 Microfilaments 544 Microfilament Structure 544 Microfilament Assembly and Disassembly 545 13.9 Myosin: The Molecular Motor of Actin Filaments 547 Conventional (Type II) Myosins 547 Unconventional Myosins 548 13.10 Muscle Contractility 552 Organization of Sarcomeres 552 The Sliding Filament Model of Muscle Contraction 553 13.11 Nonmuscle Motility 557 Actin-Binding Proteins 558 13.12 Cellular Motility 560 13.13 Actin?Dependent Processes During Development 564 Axonal Outgrowth 564 13.14 The Bacterial Cytoskeleton 567 THE HUMAN PERSPECTIVE 568 The Role of Cilia in Development and Disease 568 EXPERIMENTAL PATHWAYS 569 I. The Step Size of Kinesin 569 II. Studying Actin?Based Motility without Cells 571 14 Cell Division 578 14.1 The Cell Cycle 579 Phases of the Cell Cycle 579 Cell Cycles in Vivo 580 14.2 Regulation of the Cell Cycle 581 14.3 Control of the Cell Cycle: The Role of Protein Kinases 582 Cyclin Binding 583 Cdk Phosphorylation/Dephosphorylation 583 Cdk Inhibitors 584 Controlled Proteolysis 584 Subcellular Localization 584 14.4 Control of the Cell Cycle: Checkpoints, Cdk Inhibitors, and Cellular Responses 586 14.5 M Phase: Mitosis and Cytokinesis 588 14.6 Prophase 588 Formation of the Mitotic Chromosome 588 Centromeres and Kinetochores 590 Formation of the Mitotic Spindle 591 The Dissolution of the Nuclear Envelope and Partitioning of Cytoplasmic Organelles 594 14.7 Prometaphase 594 14.8 Metaphase 596 14.9 Anaphase 598 The Role of Proteolysis in Progression through Mitosis 598 The Events of Anaphase 600 Forces Required for Chromosome Movements at Anaphase 601 The Spindle Assembly Checkpoint 602 14.10 Telophase and Cytokinesis 603 Motor Proteins Required for Mitotic Movements 603 Cytokinesis 603 Cytokinesis in Plant Cells: Formation of the Cell Plate 607 14.11 Meiosis 608 14.12 The Stages of Meiosis 610 14.13 Genetic Recombination during Meiosis 613 THE HUMAN PERSPECTIVE 615 Meiotic Nondisjunction and Its Consequences 615 EXPERIMENTAL PATHWAYS 616 The Discovery and Characterization of MPF 616 15 Cell Signaling Pathways 624 15.1 The Basic Elements of Cell Signaling Systems 625 15.2 A Survey of Extracellular Messengers and their Receptors 628 15.3 Signal Transduction by G Protein?Coupled Receptors 629 Receptors 629 G Proteins 630 Termination of the Response 631 Bacterial Toxins 632 15.4 Second Messengers 632 The Discovery of Cyclic AMP 633 Phosphatidylinositol?Derived Second Messengers 633 Phospholipase C 635 15.5 The Specificity of G Protein?Coupled Responses 636 15.6 Regulation of Blood Glucose Levels 636 Glucose Mobilization: An Example of a Response Induced by cAMP 637 Signal Amplification 638 Other Aspects of cAMP Signal Transduction Pathways 638 15.7 The Role of GPCRs in Sensory Perception 640 15.8 Protein?Tyrosine Phosphorylation as a Mechanism for Signal Transduction 641 Receptor Dimerization 641 Protein Kinase Activation 643 Phosphotyrosine?Dependent Protein-Protein Interactions 643 Activation of Downstream Signaling Pathways 643 Ending the Response 645 15.9 The Ras?MAP Kinase Pathway 645 Accessory Proteins 645 Adapting the MAP Kinase to Transmit Different Types of Information 647 15.10 Signaling by the Insulin Receptor 648 The Insulin Receptor Is a Protein?Tyrosine Kinase 648 Insulin Receptor Substrates 1 and 2 649 Glucose Transport 650 Diabetes Mellitus 650 15.11 Signaling Pathways in Plants 651 15.12 The Role of Calcium as an Intracellular Messenger 651 IP3 and Voltage?Gated Ca2+ Channels 651 Visualizing Cytoplasmic Ca2+ Concentration in Living Cells 651 Ca2+?Binding Proteins 654 Regulating Calcium Concentrations in Plant Cells 654 15.13 Convergence, Divergence, and Cross?Talk among Different Signaling Pathways 655 15.14 The Role of NO as an Intercellular Messenger 657 NO as an Activator of Guanylyl Cyclase 658 Inhibiting Phosphodiesterase 658 15.15 Apoptosis (Programmed Cell Death) 659 The Extrinsic Pathway of Apoptosis 660 The Intrinsic Pathway of Apoptosis 661 Necroptosis 662 Signaling Cell Survival 663 THE HUMAN PERSPECTIVE 663 Disorders Associated with G Protein?Coupled Receptors 663 EXPERIMENTAL PATHWAYS 665 The Discovery and Characterization of GTP?Binding Proteins 665 16 Cancer 673 16.1 Basic Properties of a Cancer Cell 674 16.2 The Causes of Cancer 677 16.3 The Genetics of Cancer 678 16.4 An Overview of Tumor?Suppressor Genes and Oncogenes 680 16.5 Tumor?Suppressor Genes: The RB Gene 681 16.6 Tumor?Suppressor Genes: The TP53 Gene 684 The Role of p53: Guardian of the Genome 684 The Role of p53 in Promoting Senescence 686 16.7 Other Tumor?Suppressor Genes 687 16.8 Oncogenes 688 Oncogenes That Encode Growth Factors or Their Receptors 688 Oncogenes That Encode Cytoplasmic Protein Kinases 689 Oncogenes That Encode Transcription Factors 689 Oncogenes That Encode Proteins That Affect the Epigenetic State of Chromatin 689 Oncogenes That Encode Metabolic Enzymes 690 Oncogenes That Encode Products That Affect Apoptosis 690 16.9 The Mutator Phenotype: Mutant Genes Involved in DNA Repair 691 16.10 MicroRNAs: A New Player in the Genetics of Cancer 691 16.11 The Cancer Genome 691 16.12 Gene?Expression Analysis 694 16.13 Strategies for Combating Cancer 696 16.14 Immunotherapy 696 16.15 Inhibiting the Activity of Cancer?Promoting Proteins 698 16.16 The Concept of a Cancer Stem Cell 701 16.17 Inhibiting the Formation of New Blood Vessels (Angiogenesis) 701 EXPERIMENTAL PATHWAYS 702 The Discovery of Oncogenes 702 17 Immunity 709 17.1 An Overview of the Immune Response 710 Innate Immune Responses 711 Adaptive Immune Responses 713 17.2 The Clonal Selection Theory as It Applies to B Cells 714 17.3 Vaccination 715 17.4 T Lymphocytes: Activation and Mechanism of Action 717 17.5 The Modular Structure of Antibodies 720 17.6 DNA Rearrangements That Produce Genes Encoding B? and T?Cell Antigen Receptors 723 17.7 Membrane?Bound Antigen Receptor Complexes 725 17.8 The Major Histocompatibility Complex 726 17.9 Distinguishing Self from Nonself 730 17.10 Lymphocytes Are Activated by Cell?Surface Signals 731 Activation of Helper T Cells by Professional APCs 731 Activation of B Cells by TH Cells 732 17.11 Signal Transduction Pathways in Lymphocyte Activation 732 THE HUMAN PERSPECTIVE 733 Autoimmune Diseases 733 EXPERIMENTAL PATHWAYS 736 The Role of the Major Histocompatibility Complex in Antigen Presentation 736 18 Techniques in Cell and Molecular Biology 742 18.1 The Light Microscope 743 Resolution 744 Visibility 745 18.2 Bright?Field and Phase?Contrast Microscopy 745 Bright?Field Light Microscopy 745 Phase?Contrast Microscopy 746 18.3 Fluorescence Microscopy (and Related Fluorescence?Based Techniques) 746 Laser Scanning Confocal Microscopy 749 Super?Resolution Fluorescence Microscopy 750 Light Sheet Fluorescence Microscopy 751 18.4 Transmission Electron Microscopy 752 18.5 Specimen Preparation for Electron Microscopy 753 Cryofixation and the Use of Frozen Specimens 754 Negative Staining 755 Shadow Casting 755 Freeze?Fracture Replication and Freeze Etching 756 18.6 Scanning Electron Microscopy 757 18.7 Atomic Force Microscopy 758 18.8 The Use of Radioisotopes 759 18.9 Cell Culture 760 18.10 The Fractionation of a Cell's Contents by Differential Centrifugation 762 18.11 Purification and Characterization of Proteins by Liquid Column Chromatography 762 Ion?Exchange Chromatography 763 Gel Filtration Chromatography 763 Affinity Chromatography 764 18.12 Determining Protein-Protein Interactions 764 18.13 Characterization of Proteins by Polyacrylamide Gel Electrophoresis 766 SDS-PAGE 767 Two?Dimensional Gel Electrophoresis 767 18.14 Characterization of Proteins by Spectrometry 767 18.15 Characterization of Proteins by Mass Spectrometry 767 18.16 Determining the Structure of Proteins and Multisubunit Complexes 768 18.17 Fractionation of Nucleic Acids 770 Separation of DNAs by Gel Electrophoresis 770 Separation of Nucleic Acids by Ultracentrifugation 771 18.18 Nucleic Acid Hybridization 773 18.19 Chemical Synthesis of DNA 774 18.20 Recombinant DNA Technology 774 Restriction Endonucleases 774 Formation of Recombinant DNAs 775 DNA Cloning 776 18.21 Enzymatic Amplification of DNA by PCR 778 Process of PCR 778 Applications of PCR 778 18.22 DNA Sequencing 780 18.23 DNA Libraries 782 Genomic Libraries 782 cDNA Libraries 783 18.24 DNA Transfer into Eukaryotic Cells and Mammalian Embryos 783 Transgenic Animals 785 Transgenic Plants 785 18.25 Gene Editing and Silencing 786 In Vitro Mutagenesis 786 Knockout Mice 787 RNA Interference 788 Genome Editing Using Engineered Nucleases 789 18.26 The Use of Antibodies 789 Glossary G-1 Additional Reading A-1 Index I-1 |
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