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دانلود کتاب Molecular biology of the cell
دانلود کتاب زیست شناسی مولکولی سلول
مشخصات کتاب
Molecular biology of the cell
ویرایش: 6th edition
نویسندگان: Alberts. Bruce
سری:
ISBN (شابک) : 9780815344322, 1315735369
ناشر: CRC Press
سال نشر: 2017
تعداد صفحات: 1465
زبان: English
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود)
حجم فایل: 111 مگابایت
قیمت کتاب (تومان) : 40,000
کلمات کلیدی مربوط به کتاب زیست شناسی مولکولی سلول: سلول ها، سیتولوژی، زیست شناسی مولکولی، زیست شناسی مولکولی
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توجه داشته باشید کتاب زیست شناسی مولکولی سلول نسخه زبان اصلی می باشد و کتاب ترجمه شده به فارسی نمی باشد. وبسایت اینترنشنال لایبرری ارائه دهنده کتاب های زبان اصلی می باشد و هیچ گونه کتاب ترجمه شده یا نوشته شده به فارسی را ارائه نمی دهد.
توضیحاتی در مورد کتاب زیست شناسی مولکولی سلول
از آنجایی که حجم اطلاعات در زیست شناسی به طور چشمگیری گسترش می یابد، برای کتاب های درسی اهمیت فزاینده ای می یابد که حجم وسیعی از دانش علمی را به اصول مختصر و مفاهیم پایدار تقسیم کنند. همانند نسخه‌های قبلی، Biology Molecular of the Cell، نسخه ششم این هدف را با نوشته‌های واضح و تصاویر زیبا محقق می‌کند. ویرایش ششم به طور گسترده با آخرین تحقیقات در زمینه زیست شناسی سلولی تجدید نظر و به روز شده است و چارچوبی استثنایی برای آموزش و یادگیری فراهم می کند.
توضیحاتی درمورد کتاب به خارجی
As the amount of information in biology expands dramatically, it becomes increasingly important for textbooks to distill the vast amount of scientific knowledge into concise principles and enduring concepts. As with previous editions, Molecular Biology of the Cell, Sixth Edition accomplishes this goal with clear writing and beautiful illustrations. The Sixth Edition has been extensively revised and updated with the latest research in the field of cell biology, and it provides an exceptional framework for teaching and learning.
فهرست مطالب
Copyright Page Preface Note to the Reader Acknowledgments Contents Special Features Detailed Contents PART I: INTRODUCTION TO THE CELL Chapter 1: Cells and Genomes THE UNIVERSAL FEATURES OF CELLS ON EARTH All Cells Store Their Hereditary Information in the Same Linear Chemical Code: DNA All Cells Replicate Their Hereditary Information by Templated Polymerization All Cells Transcribe Portions of Their Hereditary Information into the Same Intermediary Form: RNA All Cells Use Proteins as Catalysts All Cells Translate RNA into Protein in the Same Way Each Protein Is Encoded by a Specific Gene Life Requires Free Energy All Cells Function as Biochemical Factories Dealing with the Same Basic Molecular Building Blocks All Cells Are Enclosed in a Plasma Membrane Across Which Nutrients and Waste Materials Must Pass A Living Cell Can Exist with Fewer Than 500 Genes Summary THE DIVERSITY OF GENOMES AND THE TREE OF LIFE Cells Can Be Powered by a Variety of Free-Energy Sources Some Cells Fix Nitrogen and Carbon Dioxide for Others The Greatest Biochemical Diversity Exists Among Prokaryotic Cells The Tree of Life Has Three Primary Branches: Bacteria, Archaea, and Eukaryotes Some Genes Evolve Rapidly; Others Are Highly Conserved Most Bacteria and Archaea Have 1000–6000 Genes New Genes Are Generated from Preexisting Genes Gene Duplications Give Rise to Families of Related Genes Within a Single Cell Genes Can Be Transferred Between Organisms, Both in the Laboratory and in Nature Sex Results in Horizontal Exchanges of Genetic Information Within a Species The Function of a Gene Can Often Be Deduced from Its Sequence More Than 200 Gene Families Are Common to All Three Primary Branches of the Tree of Life Mutations Reveal the Functions of Genes Molecular Biology Began with a Spotlight on E. coli Summary GENETIC INFORMATION IN EUKARYOTES Eukaryotic Cells May Have Originated as Predators Modern Eukaryotic Cells Evolved from a Symbiosis Eukaryotes Have Hybrid Genomes Eukaryotic Genomes Are Big Eukaryotic Genomes Are Rich in Regulatory DNA The Genome Defines the Program of Multicellular Development Many Eukaryotes Live as Solitary Cells A Yeast Serves as a Minimal Model Eukaryote The Expression Levels of All the Genes of An Organism Can Be Monitored Simultaneously Arabidopsis Has Been Chosen Out of 300,000 Species As a Model Plant The World of Animal Cells Is Represented By a Worm, a Fly, a Fish, a Mouse, and a Human Studies in Drosophila Provide a Key to Vertebrate Development The Vertebrate Genome Is a Product of Repeated Duplications The Frog and the Zebrafish Provide Accessible Models for Vertebrate Development The Mouse Is the Predominant Mammalian Model Organism Humans Report on Their Own Peculiarities We Are All Different in Detail To Understand Cells and Organisms Will Require Mathematics, Computers, and Quantitative Information Summary PROBLEMS REFERENCES Chapter 2: Cell Chemistry and Bioenergetics THE CHEMICAL COMPONENTS OF A CELL Water Is Held Together by Hydrogen Bonds Four Types of Noncovalent Attractions Help Bring Molecules Together in Cells Some Polar Molecules Form Acids and Bases in Water A Cell Is Formed from Carbon Compounds Cells Contain Four Major Families of Small Organic Molecules The Chemistry of Cells Is Dominated by Macromolecules with Remarkable Properties Noncovalent Bonds Specify Both the Precise Shape of a Macromolecule and Its Binding to Other Molecules Summary CATALYSIS AND THE USE OF ENERGY BY CELLS Cell Metabolism Is Organized by Enzymes Biological Order Is Made Possible by the Release of Heat Energy from Cells Cells Obtain Energy by the Oxidation of Organic Molecules Oxidation and Reduction Involve Electron Transfers Enzymes Lower the Activation-Energy Barriers That Block Chemical Reactions Enzymes Can Drive Substrate Molecules Along Specific Reaction Pathways How Enzymes Find Their Substrates: The Enormous Rapidity of Molecular Motions The Free-Energy Change for a Reaction, ∆G, Determines Whether It Can Occur Spontaneously The Concentration of Reactants Influences the Free-Energy Change and a Reaction’s Direction The Standard Free-Energy Change, ∆G°, Makes It Possible to Compare the Energetics of Different Reactions The Equilibrium Constant and ∆G° Are Readily Derived from Each Other The Free-Energy Changes of Coupled Reactions Are Additive Activated Carrier Molecules Are Essential for Biosynthesis The Formation of an Activated Carrier Is Coupled to an Energetically Favorable Reaction ATP Is the Most Widely Used Activated Carrier Molecule Energy Stored in ATP Is Often Harnessed to Join Two Molecules Together NADH and NADPH Are Important Electron Carriers There Are Many Other Activated Carrier Molecules in Cells The Synthesis of Biological Polymers Is Driven by ATP Hydrolysis Summary HOW CELLS OBTAIN ENERGY FROM FOOD Glycolysis Is a Central ATP-Producing Pathway Fermentations Produce ATP in the Absence of Oxygen Glycolysis Illustrates How Enzymes Couple Oxidation to Energy Storage Organisms Store Food Molecules in Special Reservoirs Most Animal Cells Derive Their Energy from Fatty Acids Between Meals Sugars and Fats Are Both Degraded to Acetyl CoA in Mitochondria The Citric Acid Cycle Generates NADH by Oxidizing Acetyl Groups to CO2 Electron Transport Drives the Synthesis of the Majority of the ATP in Most Cells Amino Acids and Nucleotides Are Part of the Nitrogen Cycle Metabolism Is Highly Organized and Regulated Summary PROBLEMS REFERENCES Chapter 3: Proteins THE SHAPE AND STRUCTURE OF PROTEINS The Shape of a Protein Is Specified by Its Amino Acid Sequence Proteins Fold into a Conformation of Lowest Energy The α Helix and the β Sheet Are Common Folding Patterns Protein Domains Are Modular Units from Which Larger Proteins Are Built Few of the Many Possible Polypeptide Chains Will Be Useful to Cells Proteins Can Be Classified into Many Families Some Protein Domains Are Found in Many Different Proteins Certain Pairs of Domains Are Found Together in Many Proteins The Human Genome Encodes a Complex Set of Proteins, Revealing That Much Remains Unknown Larger Protein Molecules Often Contain More Than One Polypeptide Chain Some Globular Proteins Form Long Helical Filaments Many Protein Molecules Have Elongated, Fibrous Shapes Proteins Contain a Surprisingly Large Amount of Intrinsically Disordered Polypeptide Chain Covalent Cross-Linkages Stabilize Extracellular Proteins Protein Molecules Often Serve as Subunits for the Assembly of Large Structures Many Structures in Cells Are Capable of Self-Assembly Assembly Factors Often Aid the Formation of Complex Biological Structures Amyloid Fibrils Can Form from Many Proteins Amyloid Structures Can Perform Useful Functions in Cells Many Proteins Contain Low-complexity Domains that Can Form “Reversible Amyloids” Summary PROTEIN FUNCTION All Proteins Bind to Other Molecules The Surface Conformation of a Protein Determines Its Chemistry Sequence Comparisons Between Protein Family Members Highlight Crucial Ligand-Binding Sites Proteins Bind to Other Proteins Through Several Types of Interfaces Antibody Binding Sites Are Especially Versatile The Equilibrium Constant Measures Binding Strength Enzymes Are Powerful and Highly Specific Catalysts Substrate Binding Is the First Step in Enzyme Catalysis Enzymes Speed Reactions by Selectively Stabilizing Transition States Enzymes Can Use Simultaneous Acid and Base Catalysis Lysozyme Illustrates How an Enzyme Works Tightly Bound Small Molecules Add Extra Functions to Proteins Multienzyme Complexes Help to Increase the Rate of Cell Metabolism The Cell Regulates the Catalytic Activities of Its Enzymes Allosteric Enzymes Have Two or More Binding Sites That Interact Two Ligands Whose Binding Sites Are Coupled Must Reciprocally Affect Each Other’s Binding Symmetric Protein Assemblies Produce Cooperative Allosteric Transitions Many Changes in Proteins Are Driven by Protein Phosphorylation A Eukaryotic Cell Contains a Large Collection of Protein Kinases and Protein Phosphatases The Regulation of the Src Protein Kinase Reveals How a Protein Can Function as a Microprocessor Proteins That Bind and Hydrolyze GTP Are Ubiquitous Cell Regulators Regulatory Proteins GAP and GEF Control the Activity of GTP-Binding Proteins by Determining Whether GTP or GDP Is Bound Proteins Can Be Regulated by the Covalent Addition of Other Proteins An Elaborate Ubiquitin-Conjugating System Is Used to Mark Proteins Protein Complexes with Interchangeable Parts Make Efficient Use of Genetic Information A GTP-Binding Protein Shows How Large Protein Movements Can Be Generated Motor Proteins Produce Large Movements in Cells Membrane-Bound Transporters Harness Energy to Pump Molecules Through Membranes Proteins Often Form Large Complexes That Function as Protein Machines Scaffolds Concentrate Sets of Interacting Proteins Many Proteins Are Controlled by Covalent Modifications That Direct Them to Specific Sites Inside the Cell A Complex Network of Protein Interactions Underlies Cell Function Summary PROBLEMS REFERENCES PART II: BASIC GENETIC MECHANISMS Chapter 4: DNA, Chromosomes, and Genomes THE STRUCTURE AND FUNCTION OF DNA A DNA Molecule Consists of Two Complementary Chains of Nucleotides The Structure of DNA Provides a Mechanism for Heredity In Eukaryotes, DNA Is Enclosed in a Cell Nucleus Summary CHROMOSOMAL DNA AND ITS PACKAGING IN THE CHROMATIN FIBER Eukaryotic DNA Is Packaged into a Set of Chromosomes Chromosomes Contain Long Strings of Genes The Nucleotide Sequence of the Human Genome Shows How Our Genes Are Arranged Each DNA Molecule That Forms a Linear Chromosome Must Contain a Centromere, Two Telomeres, and Replication Origins DNA Molecules Are Highly Condensed in Chromosomes Nucleosomes Are a Basic Unit of Eukaryotic Chromosome Structure The Structure of the Nucleosome Core Particle Reveals How DNA Is Packaged Nucleosomes Have a Dynamic Structure, and Are Frequently Subjected to Changes Catalyzed by ATP-Dependent Chromatin Remodeling Complexes Nucleosomes Are Usually Packed Together into a Compact Chromatin Fiber Summary CHROMATIN STRUCTURE AND FUNCTION Heterochromatin Is Highly Organized and Restricts Gene Expression The Heterochromatic State Is Self-Propagating The Core Histones Are Covalently Modified at Many Different Sites Chromatin Acquires Additional Variety Through the Site-Specific Insertion of a Small Set of Histone Variants Covalent Modifications and Histone Variants Act in Concert to Control Chromosome Functions A Complex of Reader and Writer Proteins Can Spread Specific Chromatin Modifications Along a Chromosome Barrier DNA Sequences Block the Spread of Reader–Writer Complexes and thereby Separate Neighboring Chromatin Domains The Chromatin in Centromeres Reveals How Histone Variants Can Create Special Structures Some Chromatin Structures Can Be Directly Inherited Experiments with Frog Embryos Suggest that both Activating and Repressive Chromatin Structures Can Be Inherited Epigenetically Chromatin Structures Are Important for Eukaryotic Chromosome Function Summary THE GLOBAL STRUCTURE OF CHROMOSOMES Chromosomes Are Folded into Large Loops of Chromatin Polytene Chromosomes Are Uniquely Useful for Visualizing Chromatin Structures There Are Multiple Forms of Chromatin Chromatin Loops Decondense When the Genes Within Them Are Expressed Chromatin Can Move to Specific Sites Within the Nucleus to Alter Gene Expression Networks of Macromolecules Form a Set of Distinct Biochemical Environments inside the Nucleus Mitotic Chromosomes Are Especially Highly Condensed Summary HOW GENOMES EVOLVE Genome Comparisons Reveal Functional DNA Sequences by their Conservation Throughout Evolution Genome Alterations Are Caused by Failures of the Normal Mechanisms for Copying and Maintaining DNA, as well as by Transposable DNA Elements The Genome Sequences of Two Species Differ in Proportion to the Length of Time Since They Have Separately Evolved Phylogenetic Trees Constructed from a Comparison of DNA Sequences Trace the Relationships of All Organisms A Comparison of Human and Mouse Chromosomes Shows How the Structures of Genomes Diverge The Size of a Vertebrate Genome Reflects the Relative Rates of DNA Addition and DNA Loss in a Lineage We Can Infer the Sequence of Some Ancient Genomes Multispecies Sequence Comparisons Identify Conserved DNA Sequences of Unknown Function Changes in Previously Conserved Sequences Can Help Decipher Critical Steps in Evolution Mutations in the DNA Sequences That Control Gene Expression Have Driven Many of the Evolutionary Changes in Vertebrates Gene Duplication Also Provides an Important Source of Genetic Novelty During Evolution Duplicated Genes Diverge The Evolution of the Globin Gene Family Shows How DNA Duplications Contribute to the Evolution of Organisms Genes Encoding New Proteins Can Be Created by the Recombination of Exons Neutral Mutations Often Spread to Become Fixed in a Population, with a Probability That Depends on Population Size A Great Deal Can Be Learned from Analyses of the Variation Among Humans Summary PROBLEMS REFERENCES Chapter 5: DNA Replication, Repair, and Recombination THE MAINTENANCE OF DNA SEQUENCES Mutation Rates Are Extremely Low Low Mutation Rates Are Necessary for Life as We Know It Summary DNA REPLICATION MECHANISMS Base-Pairing Underlies DNA Replication and DNA Repair The DNA Replication Fork Is Asymmetrical The High Fidelity of DNA Replication Requires Several Proofreading Mechanisms Only DNA Replication in the 5ʹ-to-3ʹ Direction Allows Efficient Error Correction A Special Nucleotide-Polymerizing Enzyme Synthesizes Short RNA Primer Molecules on the Lagging Strand Special Proteins Help to Open Up the DNA Double Helix in Front of the Replication Fork A Sliding Ring Holds a Moving DNA Polymerase Onto the DNA The Proteins at a Replication Fork Cooperate to Form a Replication Machine A Strand-Directed Mismatch Repair System Removes Replication Errors That Escape from the Replication Machine DNA Topoisomerases Prevent DNA Tangling During Replication DNA Replication Is Fundamentally Similar in Eukaryotes and Bacteria Summary THE INITIATION AND COMPLETION OF DNA REPLICATION IN CHROMOSOMES DNA Synthesis Begins at Replication Origins Bacterial Chromosomes Typically Have a Single Origin of DNA Replication Eukaryotic Chromosomes Contain Multiple Origins of Replication In Eukaryotes, DNA Replication Takes Place During Only One Part of the Cell Cycle Different Regions on the Same Chromosome Replicate at Distinct Times in S Phase A Large Multisubunit Complex Binds to Eukaryotic Origins of Replication Features of the Human Genome That Specify Origins of Replication Remain to Be Discovered New Nucleosomes Are Assembled Behind the Replication Fork Telomerase Replicates the Ends of Chromosomes Telomeres Are Packaged Into Specialized Structures That Protect the Ends of Chromosomes Telomere Length Is Regulated by Cells and Organisms Summary DNA REPAIR Without DNA Repair, Spontaneous DNA Damage Would Rapidly Change DNA Sequences The DNA Double Helix Is Readily Repaired DNA Damage Can Be Removed by More Than One Pathway Coupling Nucleotide Excision Repair to Transcription Ensures That the Cell’s Most Important DNA Is Efficiently Repaired The Chemistry of the DNA Bases Facilitates Damage Detection Special Translesion DNA Polymerases Are Used in Emergencies Double-Strand Breaks Are Efficiently Repaired DNA Damage Delays Progression of the Cell Cycle Summary HOMOLOGOUS RECOMBINATION Homologous Recombination Has Common Features in All Cells DNA Base-Pairing Guides Homologous Recombination Homologous Recombination Can Flawlessly Repair Double-Strand Breaks in DNA Strand Exchange Is Carried Out by the RecA/Rad51 Protein Homologous Recombination Can Rescue Broken DNA Replication Forks Cells Carefully Regulate the Use of Homologous Recombination in DNA Repair Homologous Recombination Is Crucial for Meiosis Meiotic Recombination Begins with a Programmed Double-Strand Break Holliday Junctions Are Formed During Meiosis Homologous Recombination Produces Both Crossovers and Non-Crossovers During Meiosis Homologous Recombination Often Results in Gene Conversion Summary TRANSPOSITION AND CONSERVATIVE SITE-SPECIFIC RECOMBINATION Through Transposition, Mobile Genetic Elements Can Insert Into Any DNA Sequence DNA-Only Transposons Can Move by a Cut-and-Paste Mechanism Some Viruses Use a Transposition Mechanism to Move Themselves Into Host-Cell Chromosomes Retroviral-like Retrotransposons Resemble Retroviruses, but Lack a Protein Coat A Large Fraction of the Human Genome Is Composed of Nonretroviral Retrotransposons Different Transposable Elements Predominate in Different Organisms Genome Sequences Reveal the Approximate Times at Which Transposable Elements Have Moved Conservative Site-Specific Recombination Can Reversibly Rearrange DNA Conservative Site-Specific Recombination Can Be Used to Turn Genes On or Off Bacterial Conservative Site-Specific Recombinases Have Become Powerful Tools for Cell and Developmental Biologists Summary PROBLEMS REFERENCES Chapter 6: How Cells Read the Genome: From DNA to Protein FROM DNA TO RNA RNA Molecules Are Single-Stranded Transcription Produces RNA Complementary to One Strand of DNA RNA Polymerases Carry Out Transcription Cells Produce Different Categories of RNA Molecules Signals Encoded in DNA Tell RNA Polymerase Where to Start and Stop Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence Transcription Initiation in Eukaryotes Requires Many Proteins RNA Polymerase II Requires a Set of General Transcription Factors Polymerase II Also Requires Activator, Mediator, and Chromatin-Modifying Proteins Transcription Elongation in Eukaryotes Requires Accessory Proteins Transcription Creates Superhelical Tension Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing RNA Capping Is the First Modification of Eukaryotic Pre-mRNAs RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs Nucleotide Sequences Signal Where Splicing Occurs RNA Splicing Is Performed by the Spliceosome The Spliceosome Uses ATP Hydrolysis to Produce a Complex Series of RNA–RNA Rearrangements Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites Chromatin Structure Affects RNA Splicing RNA Splicing Shows Remarkable Plasticity Spliceosome-Catalyzed RNA Splicing Probably Evolved from Self-splicing Mechanisms RNA-Processing Enzymes Generate the 3ʹ End of Eukaryotic mRNAs Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus Noncoding RNAs Are Also Synthesized and Processed in the Nucleus The Nucleolus Is a Ribosome-Producing Factory The Nucleus Contains a Variety of Subnuclear Aggregates Summary FROM RNA TO PROTEIN An mRNA Sequence Is Decoded in Sets of Three Nucleotides tRNA Molecules Match Amino Acids to Codons in mRNA tRNAs Are Covalently Modified Before They Exit from the Nucleus Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule Editing by tRNA Synthetases Ensures Accuracy Amino Acids Are Added to the C-terminal End of a Growing Polypeptide Chain The RNA Message Is Decoded in Ribosomes Elongation Factors Drive Translation Forward and Improve Its Accuracy Many Biological Processes Overcome the Inherent Limitations of Complementary Base-Pairing Accuracy in Translation Requires an Expenditure of Free Energy The Ribosome Is a Ribozyme Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis Stop Codons Mark the End of Translation Proteins Are Made on Polyribosomes There Are Minor Variations in the Standard Genetic Code Inhibitors of Prokaryotic Protein Synthesis Are Useful as Antibiotics Quality Control Mechanisms Act to Prevent Translation of Damaged mRNAs Some Proteins Begin to Fold While Still Being Synthesized Molecular Chaperones Help Guide the Folding of Most Proteins Cells Utilize Several Types of Chaperones Exposed Hydrophobic Regions Provide Critical Signals for Protein Quality Control The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites Many Proteins Are Controlled by Regulated Destruction There Are Many Steps From DNA to Protein Summary THE RNA WORLD AND THE ORIGINS OF LIFE Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures RNA Can Both Store Information and Catalyze Chemical Reactions How Did Protein Synthesis Evolve? All Present-Day Cells Use DNA as Their Hereditary Material Summary PROBLEMS REFERENCES Chapter 7: Control of Gene Expression AN OVERVIEW OF GENE CONTROL The Different Cell Types of a Multicellular Organism Contain the Same DNA Different Cell Types Synthesize Different Sets of RNAs and Proteins External Signals Can Cause a Cell to Change the Expression of Its Genes Gene Expression Can Be Regulated at Many of the Steps in the Pathway from DNA to RNA to Protein Summary CONTROL OF TRANSCRIPTION BY SEQUENCE-SPECIFIC DNA-BINDING PROTEINS The Sequence of Nucleotides in the DNA Double Helix Can Be Read by Proteins Transcription Regulators Contain Structural Motifs That Can Read DNA Sequences Dimerization of Transcription Regulators Increases Their Affinity and Specificity for DNA Transcription Regulators Bind Cooperatively to DNA Nucleosome Structure Promotes Cooperative Binding of Transcription Regulators Summary TRANSCRIPTION REGULATORS SWITCH GENES ON AND OFF The Tryptophan Repressor Switches Genes Off Repressors Turn Genes Off and Activators Turn Them On An Activator and a Repressor Control the Lac Operon DNA Looping Can Occur During Bacterial Gene Regulation Complex Switches Control Gene Transcription in Eukaryotes A Eukaryotic Gene Control Region Consists of a Promoter Plus Many cis-Regulatory Sequences Eukaryotic Transcription Regulators Work in Groups Activator Proteins Promote the Assembly of RNA Polymerase at the Start Point of Transcription Eukaryotic Transcription Activators Direct the Modification of Local Chromatin Structure Transcription Activators Can Promote Transcription by Releasing RNA Polymerase from Promoters Transcription Activators Work Synergistically Eukaryotic Transcription Repressors Can Inhibit Transcription in Several Ways Insulator DNA Sequences Prevent Eukaryotic Transcription Regulators from Influencing Distant Genes Summary MOLECULAR GENETIC MECHANISMS THAT CREATE AND MAINTAIN SPECIALIZED CELL TYPES Complex Genetic Switches That Regulate Drosophila Development Are Built Up from Smaller Molecules The Drosophila Eve Gene Is Regulated by Combinatorial Controls Transcription Regulators Are Brought Into Play by Extracellular Signals Combinatorial Gene Control Creates Many Different Cell Types Specialized Cell Types Can Be Experimentally Reprogrammed to Become Pluripotent Stem Cells Combinations of Master Transcription Regulators Specify Cell Types by Controlling the Expression of Many Genes Specialized Cells Must Rapidly Turn Sets of Genes On and Off Differentiated Cells Maintain Their Identity Transcription Circuits Allow the Cell to Carry Out Logic Operations Summary MECHANISMS THAT REINFORCE CELL MEMORY IN plants and animals Patterns of DNA Methylation Can Be Inherited When Vertebrate Cells Divide CG-Rich Islands Are Associated with Many Genes in Mammals Genomic Imprinting Is Based on DNA Methylation Chromosome-Wide Alterations in Chromatin Structure Can Be Inherited Epigenetic Mechanisms Ensure That Stable Patterns of Gene Expression Can Be Transmitted to Daughter Cells Summary POST-TRANSCRIPTIONAL CONTROLS Transcription Attenuation Causes the Premature Termination of Some RNA Molecules Riboswitches Probably Represent Ancient Forms of Gene Control Alternative RNA Splicing Can Produce Different Forms of a Protein from the Same Gene The Definition of a Gene Has Been Modified Since the Discovery of Alternative RNA Splicing A Change in the Site of RNA Transcript Cleavage and Poly-A Addition Can Change the C-terminus of a Protein RNA Editing Can Change the Meaning of the RNA Message RNA Transport from the Nucleus Can Be Regulated Some mRNAs Are Localized to Specific Regions of the Cytosol The 5ʹ and 3ʹ Untranslated Regions of mRNAs Control Their Translation The Phosphorylation of an Initiation Factor Regulates Protein Synthesis Globally Initiation at AUG Codons Upstream of the Translation Start Can Regulate Eukaryotic Translation Initiation Internal Ribosome Entry Sites Provide Opportunities for Translational Control Changes in mRNA Stability Can Regulate Gene Expression Regulation of mRNA Stability Involves P-bodies and Stress Granules Summary REGULATION OF GENE EXPRESSION BY NONCODING RNAs Small Noncoding RNA Transcripts Regulate Many Animal and Plant Genes Through RNA Interference miRNAs Regulate mRNA Translation and Stability RNA Interference Is Also Used as a Cell Defense Mechanism RNA Interference Can Direct Heterochromatin Formation piRNAs Protect the Germ Line from Transposable Elements RNA Interference Has Become a Powerful Experimental Tool Bacteria Use Small Noncoding RNAs to Protect Themselves from Viruses Long Noncoding RNAs Have Diverse Functions in the Cell Summary PROBLEMS REFERENCES PART III: ISOLATING CELLS AND GROWING THEM IN CULTURE Chapter 8: Analyzing Cells, Molecules,and Systems ISOLATING CELLS AND GROWING THEM IN CULTURE Cells Can Be Isolated from Tissues Cells Can Be Grown in Culture Eukaryotic Cell Lines Are a Widely Used Source of Homogeneous Cells Hybridoma Cell Lines Are Factories That Produce Monoclonal Antibodies Summary PURIFYING PROTEINS Cells Can Be Separated into Their Component Fractions Cell Extracts Provide Accessible Systems to Study Cell Functions Proteins Can Be Separated by Chromatography Immunoprecipitation Is a Rapid Affinity Purification Method Genetically Engineered Tags Provide an Easy Way to Purify Proteins Purified Cell-free Systems Are Required for the Precise Dissection of Molecular Functions Summary ANALYZING PROTEINS Proteins Can Be Separated by SDS Polyacrylamide-Gel Electrophoresis Two-Dimensional Gel Electrophoresis Provides Greater Protein Separation Specific Proteins Can Be Detected by Blotting with Antibodies Hydrodynamic Measurements Reveal the Size and Shape of a Protein Complex Mass Spectrometry Provides a Highly Sensitive Method for Identifying Unknown Proteins Sets of Interacting Proteins Can Be Identified by Biochemical Methods Optical Methods Can Monitor Protein Interactions Protein Function Can Be Selectively Disrupted With Small Molecules Protein Structure Can Be Determined Using X-Ray Diffraction NMR Can Be Used to Determine Protein Structure in Solution Protein Sequence and Structure Provide Clues About Protein Function Summary ANALYZING AND MANIPULATING DNA Restriction Nucleases Cut Large DNA Molecules into Specific Fragments Gel Electrophoresis Separates DNA Molecules of Different Sizes Purified DNA Molecules Can Be Specifically Labeled with Radioisotopes or Chemical Markers in vitro Genes Can Be Cloned Using Bacteria An Entire Genome Can Be Represented in a DNA Library Genomic and cDNA Libraries Have Different Advantages and Drawbacks Hybridization Provides a Powerful, But Simple Way to Detect Specific Nucleotide Sequences Genes Can Be Cloned in vitro Using PCR PCR Is Also Used for Diagnostic and Forensic Applications Both DNA and RNA Can Be Rapidly Sequenced To Be Useful, Genome Sequences Must Be Annotated DNA Cloning Allows Any Protein to be Produced in Large Amounts Summary STUDYING GENE EXPRESSION AND FUNCTION Classical Genetics Begins by Disrupting a Cell Process by Random Mutagenesis Genetic Screens Identify Mutants with Specific Abnormalities Mutations Can Cause Loss or Gain of Protein Function Complementation Tests Reveal Whether Two Mutations Are in the Same Gene or Different Genes Gene Products Can Be Ordered in Pathways by Epistasis Analysis Mutations Responsible for a Phenotype Can Be Identified Through DNA Analysis Rapid and Cheap DNA Sequencing Has Revolutionized Human Genetic Studies Linked Blocks of Polymorphisms Have Been Passed Down from Our Ancestors Polymorphisms Can Aid the Search for Mutations Associated with Disease Genomics Is Accelerating the Discovery of Rare Mutations That Predispose Us to Serious Disease Reverse Genetics Begins with a Known Gene and Determines Which Cell Processes Require Its Function Animals and Plants Can Be Genetically Altered The Bacterial CRISPR System Has Been Adapted to Edit Genomes in a Wide Variety of Species Large Collections of Engineered Mutations Provide a Tool for Examining the Function of Every Gene in an Organism RNA Interference Is a Simple and Rapid Way to Test Gene Function Reporter Genes Reveal When and Where a Gene Is Expressed In situ Hybridization Can Reveal the Location of mRNAs and Noncoding RNAs Expression of Individual Genes Can Be Measured Using Quantitative RT-PCR Analysis of mRNAs by Microarray or RNA-seq Provides a Snapshot of Gene Expression Genome-wide Chromatin Immunoprecipitation Identifies Sites on the Genome Occupied by Transcription Regulators Ribosome Profiling Reveals Which mRNAs Are Being Translated in the Cell Recombinant DNA Methods Have Revolutionized Human Health Transgenic Plants Are Important for Agriculture Summary MATHEMATICAL ANALYSIS OF CELL FUNCTIONS Regulatory Networks Depend on Molecular Interactions Differential Equations Help Us Predict Transient Behavior Both Promoter Activity and Protein Degradation Affect the Rate of Change of Protein Concentration The Time Required to Reach Steady State Depends on Protein Lifetime Quantitative Methods Are Similar for Transcription Repressors and Activators Negative Feedback Is a Powerful Strategy in Cell Regulation Delayed Negative Feedback Can Induce Oscillations DNA Binding By a Repressor or an Activator Can Be Cooperative Positive Feedback Is Important for Switchlike Responses and Bistability Robustness Is an Important Characteristic of Biological Networks Two Transcription Regulators That Bind to the Same Gene Promoter Can Exert Combinatorial Control An Incoherent Feed-forward Interaction Generates Pulses A Coherent Feed-forward Interaction Detects Persistent Inputs The Same Network Can Behave Differently in Different Cells Due to Stochastic Effects Several Computational Approaches Can Be Used to Model the Reactions in Cells Statistical Methods Are Critical For the Analysis of Biological Data Summary PROBLEMS REFERENCES Chapter 9: Visualizing Cells LOOKING AT CELLS IN THE LIGHT MICROSCOPE The Light Microscope Can Resolve Details 0.2 μm Apart Photon Noise Creates Additional Limits to Resolution When Light Levels Are Low Living Cells Are Seen Clearly in a Phase-Contrast or a Differential-Interference-Contrast Microscope Images Can Be Enhanced and Analyzed by Digital Techniques Intact Tissues Are Usually Fixed and Sectioned Before Microscopy Specific Molecules Can Be Located in Cells by Fluorescence Microscopy Antibodies Can Be Used to Detect Specific Molecules Imaging of Complex Three-Dimensional Objects Is Possible with the Optical Microscope The Confocal Microscope Produces Optical Sections by Excluding Out-of-Focus Light Individual Proteins Can Be Fluorescently Tagged in Living Cells and Organisms Protein Dynamics Can Be Followed in Living Cells Light-Emitting Indicators Can Measure Rapidly Changing Intracellular Ion Concentrations Single Molecules Can Be Visualized by Total Internal Reflection Fluorescence Microscopy Individual Molecules Can Be Touched, Imaged, and Moved Using Atomic Force Microscopy Superresolution Fluorescence Techniques Can Overcome Diffraction-Limited Resolution Superresolution Can Also be Achieved Using Single-Molecule Localization Methods Summary LOOKING AT CELLS AND MOLECULES IN THE ELECTRON MICROSCOPE The Electron Microscope Resolves the Fine Structure of the Cell Biological Specimens Require Special Preparation for Electron Microscopy Specific Macromolecules Can Be Localized by Immunogold Electron Microscopy Different Views of a Single Object Can Be Combined to Give a Three-Dimensional Reconstruction Images of Surfaces Can Be Obtained by Scanning Electron Microscopy Negative Staining and Cryoelectron Microscopy Both Allow Macromolecules to Be Viewed at High Resolution Multiple Images Can Be Combined to Increase Resolution Summary PROBLEMS REFERENCES PART IV: INTERNAL ORGANIZATION OF THE CELL Chapter 10: Membrane Structure THE LIPID BILAYER Phosphoglycerides, Sphingolipids, and Sterols Are the Major Lipids in Cell Membranes Phospholipids Spontaneously Form Bilayers The Lipid Bilayer Is a Two-dimensional Fluid The Fluidity of a Lipid Bilayer Depends on Its Composition Despite Their Fluidity, Lipid Bilayers Can Form Domains of Different Compositions Lipid Droplets Are Surrounded by a Phospholipid Monolayer The Asymmetry of the Lipid Bilayer Is Functionally Important Glycolipids Are Found on the Surface of All Eukaryotic Plasma Membranes Summary MEMBRANE PROTEINS Membrane Proteins Can Be Associated with the Lipid Bilayer in Various Ways Lipid Anchors Control the Membrane Localization of Some Signaling Proteins In Most Transmembrane Proteins, the Polypeptide Chain Crosses the Lipid Bilayer in an α-Helical Conformation Transmembrane α Helices Often Interact with One Another Some β Barrels Form Large Channels Many Membrane Proteins Are Glycosylated Membrane Proteins Can Be Solubilized and Purified in Detergents Bacteriorhodopsin Is a Light-driven Proton (H+) Pump That Traverses the Lipid Bilayer as Seven α Helices Membrane Proteins Often Function as Large Complexes Many Membrane Proteins Diffuse in the Plane of the Membrane Cells Can Confine Proteins and Lipids to Specific Domains Within a Membrane The Cortical Cytoskeleton Gives Membranes Mechanical Strength and Restricts Membrane Protein Diffusion Membrane-bending Proteins Deform Bilayers Summary PROBLEMS REFERENCES Chapter 11: Membrane Transport of Small Molecules and the Electrical Properties of Membranes PRINCIPLES OF MEMBRANE TRANSPORT Protein-Free Lipid Bilayers Are Impermeable to Ions There Are Two Main Classes of Membrane Transport Proteins: Transporters and Channels Active Transport Is Mediated by Transporters Coupled to an Energy Source Summary TRANSPORTERS AND ACTIVE MEMBRANE TRANSPORT Active Transport Can Be Driven by Ion-Concentration Gradients Transporters in the Plasma Membrane Regulate Cytosolic pH An Asymmetric Distribution of Transporters in Epithelial Cells Underlies the Transcellular Transport of Solutes There Are Three Classes of ATP-Driven Pumps A P-type ATPase Pumps Ca2+ into the Sarcoplasmic Reticulum in Muscle Cells The Plasma Membrane Na+-K+ Pump Establishes Na+ and K+ Gradients Across the Plasma Membrane ABC Transporters Constitute the Largest Family of Membrane Transport Proteins Summary CHANNELS AND THE ELECTRICAL PROPERTIES Aquaporins Are Permeable to Water But Impermeable to Ions Ion Channels Are Ion-Selective and Fluctuate Between Open and Closed States The Membrane Potential in Animal Cells Depends Mainly on K+ Leak Channels and the K+ Gradient Across the Plasma Membrane The Resting Potential Decays Only Slowly When the Na+-K+ Pump Is Stopped The Three-Dimensional Structure of a Bacterial K+ Channel Shows How an Ion Channel Can Work Mechanosensitive Channels Protect Bacterial Cells Against Extreme Osmotic Pressures The Function of a Neuron Depends on Its Elongated Structure Voltage-Gated Cation Channels Generate Action Potentials in Electrically Excitable Cells The Use of Channelrhodopsins Has Revolutionized the Study of Neural Circuits Myelination Increases the Speed and Efficiency of Action Potential Propagation in Nerve Cells Patch-Clamp Recording Indicates That Individual Ion Channels Open in an All-or-Nothing Fashion Voltage-Gated Cation Channels Are Evolutionarily and Structurally Related Different Neuron Types Display Characteristic Stable Firing Properties Transmitter-Gated Ion Channels Convert Chemical Signals into Electrical Ones at Chemical Synapses Chemical Synapses Can Be Excitatory or Inhibitory The Acetylcholine Receptors at the Neuromuscular Junction Are Excitatory Transmitter-Gated Cation Channels Neurons Contain Many Types of Transmitter-Gated Channels Many Psychoactive Drugs Act at Synapses Neuromuscular Transmission Involves the Sequential Activation of Five Different Sets of Ion Channels Single Neurons Are Complex Computation Devices Neuronal Computation Requires a Combination of at Least Three Kinds of K+ Channels Long-Term Potentiation (LTP) in the Mammalian Hippocampus Depends on Ca2+ Entry Through NMDA-Receptor Channels Summary PROBLEMS REFERENCES Chapter 12: Intracellular Compartments and Protein Sorting THE COMPARTMENTALIZATION OF CELLS All Eukaryotic Cells Have the Same Basic Set of Membrane-enclosed Organelles Evolutionary Origins May Help Explain the Topological Relationships of Organelles Proteins Can Move Between Compartments in Different Ways Signal Sequences and Sorting Receptors Direct Proteins to the Correct Cell Address Most Organelles Cannot Be Constructed De Novo: They Require Information in the Organelle Itself Summary THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL Nuclear Pore Complexes Perforate the Nuclear Envelope Nuclear Localization Signals Direct Nuclear Proteins to the Nucleus Nuclear Import Receptors Bind to Both Nuclear Localization Signals and NPC Proteins Nuclear Export Works Like Nuclear Import, But in Reverse The Ran GTPase Imposes Directionality on Transport Through NPCs Transport Through NPCs Can Be Regulated by Controlling Access to the Transport Machinery During Mitosis the Nuclear Envelope Disassembles Summary THE TRANSPORT OF PROTEINS INTO MITOCHONDRIA AND CHLOROPLASTS Translocation into Mitochondria Depends on Signal Sequences and Protein Translocators Mitochondrial Precursor Proteins Are Imported as Unfolded Polypeptide Chains ATP Hydrolysis and a Membrane Potential Drive Protein Import Into the Matrix Space Bacteria and Mitochondria Use Similar Mechanisms to Insert Porins into their Outer Membrane Transport Into the Inner Mitochondrial Membrane and Intermembrane Space Occurs Via Several Routes Two Signal Sequences Direct Proteins to the Thylakoid Membrane in Chloroplasts Summary PEROXISOMES Peroxisomes Use Molecular Oxygen and Hydrogen Peroxide to Perform Oxidation Reactions A Short Signal Sequence Directs the Import of Proteins into Peroxisomes Summary THE ENDOPLASMIC RETICULUM The ER Is Structurally and Functionally Diverse Signal Sequences Were First Discovered in Proteins Imported into the Rough ER A Signal-Recognition Particle (SRP) Directs the ER Signal Sequence to a Specific Receptor in the Rough ER Membrane The Polypeptide Chain Passes Through an Aqueous Channel in the Translocator Translocation Across the ER Membrane Does Not Always Require Ongoing Polypeptide Chain Elongation In Single-Pass Transmembrane Proteins, a Single Internal ER Signal Sequence Remains in the Lipid Bilayer as a Membrane-spanning α Helix Combinations of Start-Transfer and Stop-Transfer Signals Determine the Topology of Multipass Transmembrane Proteins ER Tail-anchored Proteins Are Integrated into the ER Membrane by a Special Mechanism Translocated Polypeptide Chains Fold and Assemble in the Lumen of the Rough ER Most Proteins Synthesized in the Rough ER Are Glycosylated by the Addition of a Common N-Linked Oligosaccharide Oligosaccharides Are Used as Tags to Mark the State of Protein Folding Improperly Folded Proteins Are Exported from the ER and Degraded in the Cytosol Misfolded Proteins in the ER Activate an Unfolded Protein Response Some Membrane Proteins Acquire a Covalently Attached Glycosylphosphatidylinositol (GPI) Anchor The ER Assembles Most Lipid Bilayers Summary PROBLEMS REFERENCES Chapter 13: Intracellular Membrane Traffic THE MOLECULAR MECHANISMS OF MEMBRANE TRANSPORT AND THE MAINTENANCE OF COMPARTMENTAL DIVERSITY There Are Various Types of Coated Vesicles The Assembly of a Clathrin Coat Drives Vesicle Formation Adaptor Proteins Select Cargo into Clathrin-Coated Vesicles Phosphoinositides Mark Organelles and Membrane Domains Membrane-Bending Proteins Help Deform the Membrane During Vesicle Formation Cytoplasmic Proteins Regulate the Pinching-Off and Uncoating of Coated Vesicles Monomeric GTPases Control Coat Assembly Not All Transport Vesicles Are Spherical Rab Proteins Guide Transport Vesicles to Their Target Membrane Rab Cascades Can Change the Identity of an Organelle SNAREs Mediate Membrane Fusion Interacting SNAREs Need to Be Pried Apart Before They Can Function Again Summary TRANSPORT FROM THE ER THROUGH THE GOLGI APPARATUS Proteins Leave the ER in COPII-Coated Transport Vesicles Only Proteins That Are Properly Folded and Assembled Can Leave the ER Vesicular Tubular Clusters Mediate Transport from the ER to the Golgi Apparatus The Retrieval Pathway to the ER Uses Sorting Signals Many Proteins Are Selectively Retained in the Compartments in Which They Function The Golgi Apparatus Consists of an Ordered Series of Compartments Oligosaccharide Chains Are Processed in the Golgi Apparatus Proteoglycans Are Assembled in the Golgi Apparatus What Is the Purpose of Glycosylation? Transport Through the Golgi Apparatus May Occur by Cisternal Maturation Golgi Matrix Proteins Help Organize the Stack Summary TRANSPORT FROM THE TRANS GOLGI NETWORK TO LYSOSOMES Lysosomes Are the Principal Sites of Intracellular Digestion Lysosomes Are Heterogeneous Plant and Fungal Vacuoles Are Remarkably Versatile Lysosomes Multiple Pathways Deliver Materials to Lysosomes Autophagy Degrades Unwanted Proteins and Organelles A Mannose 6-Phosphate Receptor Sorts Lysosomal Hydrolases in the Trans Golgi Network Defects in the GlcNAc Phosphotransferase Cause a Lysosomal Storage Disease in Humans Some Lysosomes and Multivesicular Bodies Undergo Exocytosis Summary TRANSPORT INTO THE CELL FROM THE PLASMA MEMBRANE: ENDOCYTOSIS Pinocytic Vesicles Form from Coated Pits in the Plasma Membrane Not All Pinocytic Vesicles Are Clathrin-Coated Cells Use Receptor-Mediated Endocytosis to Import Selected Extracellular Macromolecules Specific Proteins Are Retrieved from Early Endosomes and Returned to the Plasma Membrane Plasma Membrane Signaling Receptors are Down-Regulated by Degradation in Lysosomes Early Endosomes Mature into Late Endosomes ESCRT Protein Complexes Mediate the Formation of Intralumenal Vesicles in Multivesicular Bodies Recycling Endosomes Regulate Plasma Membrane Composition Specialized Phagocytic Cells Can Ingest Large Particles Summary TRANSPORT FROM THE TRANS GOLGI NETWORK TO THE CELL EXTERIOR: EXOCYTOSIS Many Proteins and Lipids Are Carried Automatically from the Trans Golgi Network (TGN) to the Cell Surface Secretory Vesicles Bud from the Trans Golgi Network Precursors of Secretory Proteins Are Proteolytically Processed During the Formation of Secretory Vesicles Secretory Vesicles Wait Near the Plasma Membrane Until Signaled to Release Their Contents For Rapid Exocytosis, Synaptic Vesicles Are Primed at the Presynaptic Plasma Membrane Synaptic Vesicles Can Form Directly from Endocytic Vesicles Secretory Vesicle Membrane Components Are Quickly Removed from the Plasma Membrane Some Regulated Exocytosis Events Serve to Enlarge the Plasma Membrane Polarized Cells Direct Proteins from the Trans Golgi Network to the Appropriate Domain of the Plasma Membrane Summary PROBLEMS REFERENCES Chapter 14: Energy Conversion: Mitochondria and Chloroplasts THE MITOCHONDRION The Mitochondrion Has an Outer Membrane and an Inner Membrane The Inner Membrane Cristae Contain the Machinery for Electron Transport and ATP Synthesis The Citric Acid Cycle in the Matrix Produces NADH Mitochondria Have Many Essential Roles in Cellular Metabolism A Chemiosmotic Process Couples Oxidation Energy to ATP Production The Energy Derived from Oxidation Is Stored as an Electrochemical Gradient Summary THE PROTON PUMPS OF THE ELECTRON-TRANSPORT CHAIN The Redox Potential Is a Measure of Electron Affinities Electron Transfers Release Large Amounts of Energy Transition Metal Ions and Quinones Accept and Release NADH Transfers Its Electrons to Oxygen Through Three Large Enzyme Complexes Embedded in the Inner Membrane The NADH Dehydrogenase Complex Contains Separate Modules for Electron Transport and Proton Pumping Cytochrome c Reductase Takes Up and Releases Protons on the Opposite Side of the Crista Membrane, Thereby Pumping Protons The Cytochrome c Oxidase Complex Pumps Protons and Reduces O2 Using a Catalytic Iron–Copper Center The Respiratory Chain Forms a Supercomplex in the Crista Membrane Protons Can Move Rapidly Through Proteins Along Predefined Pathways Summary ATP PRODUCTION IN MITOCHONDRIA The Large Negative Value of ∆G for ATP Hydrolysis Makes ATP Useful to the Cell The ATP Synthase Is a Nanomachine that Produces ATP by Rotary Catalysis Proton-driven Turbines Are of Ancient Origin Mitochondrial Cristae Help to Make ATP Synthesis Efficient Special Transport Proteins Exchange ATP and ADP Through the Inner Membrane Chemiosmotic Mechanisms First Arose in Bacteria Summary CHLOROPLASTS AND PHOTOSYNTHESIS Chloroplasts Resemble Mitochondria But Have a Separate Thylakoid Compartment Chloroplasts Capture Energy from Sunlight and Use It to Fix Carbon Carbon Fixation Uses ATP and NADPH to Convert CO2 into Sugars Sugars Generated by Carbon Fixation Can Be Stored as Starch or Consumed to Produce ATP The Thylakoid Membranes of Chloroplasts Contain the Protein Complexes Required for Photosynthesis and ATP Generation Chlorophyll–Protein Complexes Can Transfer Either Excitation Energy or Electrons A Photosystem Consists of an Antenna Complex and a Reaction Center The Thylakoid Membrane Contains Two Different Photosystems Working in Series Photosystem II Uses a Manganese Cluster to Withdraw Electrons From Water The Cytochrome b6-f Complex Connects Photosystem II to Photosystem I Photosystem I Carries Out the Second Charge-Separation Step in the Z Scheme The Chloroplast ATP Synthase Uses the Proton Gradient Generated by the Photosynthetic Light Reactions to Produce ATP All Photosynthetic Reaction Centers Have Evolved From a Common Ancestor The Proton-Motive Force for ATP Production in Mitochondria and Chloroplasts Is Essentially the Same Chemiosmotic Mechanisms Evolved in Stages By Providing an Inexhaustible Source of Reducing Power, Photosynthetic Bacteria Overcame a Major Evolutionary Obstacle The Photosynthetic Electron-Transport Chains of Cyanobacteria Produced Atmospheric Oxygen and Permitted New Life-Forms Summary THE GENETIC SYSTEMS OF MITOCHONDRIA AND CHLOROPLASTS The Genetic Systems of Mitochondria and Chloroplasts Resemble Those of Prokaryotes Over Time, Mitochondria and Chloroplasts Have Exported Most of Their Genes to the Nucleus by Gene Transfer The Fission and Fusion of Mitochondria Are Topologically Complex Processes Animal Mitochondria Contain the Simplest Genetic Systems Known Mitochondria Have a Relaxed Codon Usage and Can Have a Variant Genetic Code Chloroplasts and Bacteria Share Many Striking Similarities Organelle Genes Are Maternally Inherited in Animals and Plants Mutations in Mitochondrial DNA Can Cause Severe Inherited Diseases The Accumulation of Mitochondrial DNA Mutations Is a Contributor to Aging Why Do Mitochondria and Chloroplasts Maintain a Costly Separate System for DNA Transcription and Translation? Summary PROBLEMS REFERENCES Chapter 15: Cell Signaling PRINCIPLES OF CELL SIGNALING Extracellular Signals Can Act Over Short or Long Distances Extracellular Signal Molecules Bind to Specific Receptors Each Cell Is Programmed to Respond to Specific Combinations of Extracellular Signals There Are Three Major Classes of Cell-Surface Receptor Proteins Cell-Surface Receptors Relay Signals Via Intracellular Signaling Molecules Intracellular Signals Must Be Specific and Precise in a Noisy Cytoplasm Intracellular Signaling Complexes Form at Activated Receptors Modular Interaction Domains Mediate Interactions Between Intracellular Signaling Proteins The Relationship Between Signal and Response Varies in Different Signaling Pathways The Speed of a Response Depends on the Turnover of Signaling Molecules Cells Can Respond Abruptly to a Gradually Increasing Signal Positive Feedback Can Generate an All-or-None Response Negative Feedback is a Common Motif in Signaling Systems Cells Can Adjust Their Sensitivity to a Signal Summary SIGNALING THROUGH G-PROTEIN-COUPLED RECEPTORS Trimeric G Proteins Relay Signals From GPCRs Some G Proteins Regulate the Production of Cyclic AMP Cyclic-AMP-Dependent Protein Kinase (PKA) Mediates Most of the Effects of Cyclic AMP Some G Proteins Signal Via Phospholipids Ca2+ Functions as a Ubiquitous Intracellular Mediator Feedback Generates Ca2+ Waves and Oscillations Ca2+/Calmodulin-Dependent Protein Kinases Mediate Many Responses to Ca2+ Signals Some G Proteins Directly Regulate Ion Channels Smell and Vision Depend on GPCRs That Regulate Ion Channels Nitric Oxide Is a Gaseous Signaling Mediator That Passes Between Cells Second Messengers and Enzymatic Cascades Amplify Signals GPCR Desensitization Depends on Receptor Phosphorylation Summary SIGNALING THROUGH ENZYME-COUPLED RECEPTORS Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate Themselves Phosphorylated Tyrosines on RTKs Serve as Docking Sites for Intracellular Signaling Proteins Proteins with SH2 Domains Bind to Phosphorylated Tyrosines The GTPase Ras Mediates Signaling by Most RTKs Ras Activates a MAP Kinase Signaling Module Scaffold Proteins Help Prevent Cross-talk Between Parallel MAP Kinase Modules Rho Family GTPases Functionally Couple Cell-Surface Receptors to the Cytoskeleton PI 3-Kinase Produces Lipid Docking Sites in the Plasma Membrane The PI-3-Kinase–Akt Signaling Pathway Stimulates Animal Cells to Survive and Grow RTKs and GPCRs Activate Overlapping Signaling Pathways Some Enzyme-Coupled Receptors Associate with Cytoplasmic Tyrosine Kinases Cytokine Receptors Activate the JAK–STAT Signaling Pathway Protein Tyrosine Phosphatases Reverse Tyrosine Phosphorylations Signal Proteins of the TGFβ Superfamily Act Through Receptor Serine/Threonine Kinases and Smads Summary ALTERNATIVE SIGNALING ROUTES IN GENE REGULATION The Receptor Notch Is a Latent Transcription Regulatory Protein Wnt Proteins Bind to Frizzled Receptors and Inhibit the Degradation of β-Catenin Hedgehog Proteins Bind to Patched, Relieving Its Inhibition of Smoothened Many Stressful and Inflammatory Stimuli Act Through an NFκB-Dependent Signaling Pathway Nuclear Receptors Are Ligand-Modulated Transcription Regulators Circadian Clocks Contain Negative Feedback Loops That Control Gene Expression Three Proteins in a Test Tube Can Reconstitute a Cyanobacterial Circadian Clock Summary SIGNALING IN PLANTS Multicellularity and Cell Communication Evolved Independently in Plants and Animals Receptor Serine/Threonine Kinases Are the Largest Class of Cell-Surface Receptors in Plants Ethylene Blocks the Degradation of Specific Transcription Regulatory Proteins in the Nucleus Regulated Positioning of Auxin Transporters Patterns Plant Growth Phytochromes Detect Red Light, and Cryptochromes Detect Blue Light Summary PROBLEMS REFERENCES Chapter 16: The Cytoskeleton FUNCTION AND ORIGIN OF THE CYTOSKELETON Cytoskeletal Filaments Adapt to Form Dynamic or Stable Structures The Cytoskeleton Determines Cellular Organization and Polarity Filaments Assemble from Protein Subunits That Impart Specific Physical and Dynamic Properties Accessory Proteins and Motors Regulate Cytoskeletal Filaments Bacterial Cell Organization and Division Depend on Homologs of Eukaryotic Cytoskeletal Proteins Summary ACTIN AND ACTIN-BINDING PROTEINS Actin Subunits Assemble Head-to-Tail to Create Flexible, Polar Filaments Nucleation Is the Rate-Limiting Step in the Formation of Actin Filaments Actin Filaments Have Two Distinct Ends That Grow at Different Rates ATP Hydrolysis Within Actin Filaments Leads to Treadmilling at Steady State The Functions of Actin Filaments Are Inhibited by Both Polymer-stabilizing and Polymer-destabilizing Chemicals Actin-Binding Proteins Influence Filament Dynamics and Organization Monomer Availability Controls Actin Filament Assembly Actin-Nucleating Factors Accelerate Polymerization and Generate Branched or Straight Filaments Actin-Filament-Binding Proteins Alter Filament Dynamics Severing Proteins Regulate Actin Filament Depolymerization Higher-Order Actin Filament Arrays Influence Cellular Mechanical Properties and Signaling Bacteria Can Hijack the Host Actin Cytoskeleton Summary MYOSIN AND ACTIN Actin-Based Motor Proteins Are Members of the Myosin Superfamily Myosin Generates Force by Coupling ATP Hydrolysis to Conformational Changes Sliding of Myosin II Along Actin Filaments Causes Muscles to Contract A Sudden Rise in Cytosolic Ca2+ Concentration Initiates Muscle Contraction Heart Muscle Is a Precisely Engineered Machine Actin and Myosin Perform a Variety of Functions in Non-Muscle Cells Summary MICROTUBULES Microtubules Are Hollow Tubes Made of Protofilaments Microtubules Undergo Dynamic Instability Microtubule Functions Are Inhibited by Both Polymer-stabilizing and Polymer-destabilizing Drugs A Protein Complex Containing γ-Tubulin Nucleates Microtubules Microtubules Emanate from the Centrosome in Animal Cells Microtubule-Binding Proteins Modulate Filament Dynamics and Organization Microtubule Plus-End-Binding Proteins Modulate Microtubule Dynamics and Attachments Tubulin-Sequestering and Microtubule-Severing Proteins Destabilize Microtubules Two Types of Motor Proteins Move Along Microtubules Microtubules and Motors Move Organelles and Vesicles Construction of Complex Microtubule Assemblies Requires Microtubule Dynamics and Motor Proteins Motile Cilia and Flagella Are Built from Microtubules and Dyneins Primary Cilia Perform Important Signaling Functions in Animal Cells Summary INTERMEDIATE FILAMENTS AND SEPTINS Intermediate Filament Structure Depends on the Lateral Bundling and Twisting of Coiled-Coils Intermediate Filaments Impart Mechanical Stability to Animal Cells Linker Proteins Connect Cytoskeletal Filaments and Bridge the Nuclear Envelope Septins Form Filaments That Regulate Cell Polarity Summary CELL POLARIZATION AND MIGRATION Many Cells Can Crawl Across a Solid Substratum Actin Polymerization Drives Plasma Membrane Protrusion Lamellipodia Contain All of the Machinery Required for Cell Motility Myosin Contraction and Cell Adhesion Allow Cells to Pull Themselves Forward Cell Polarization Is Controlled by Members of the Rho Protein Family Extracellular Signals Can Activate the Three Rho Protein Family Members External Signals Can Dictate the Direction of Cell Migration Communication Among Cytoskeletal Elements Coordinates Whole-Cell Polarization and Locomotion Summary PROBLEMS REFERENCES Chapter 17: The Cell Cycle OVERVIEW OF THE CELL CYCLE The Eukaryotic Cell Cycle Usually Consists of Four Phases Cell-Cycle Control Is Similar in All Eukaryotes Cell-Cycle Progression Can Be Studied in Various Ways Summary THE CELL-CYCLE CONTROL SYSTEM The Cell-Cycle Control System Triggers the Major Events of the Cell Cycle The Cell-Cycle Control System Depends on Cyclically Activated Cyclin-Dependent Protein Kinases (Cdks) Cdk Activity Can Be Suppressed By Inhibitory Phosphorylation and Cdk Inhibitor Proteins (CKIs) Regulated Proteolysis Triggers the Metaphase-to-Anaphase Transition Cell-Cycle Control Also Depends on Transcriptional Regulation The Cell-Cycle Control System Functions as a Network of Biochemical Switches Summary S PHASE S-Cdk Initiates DNA Replication Once Per Cycle Chromosome Duplication Requires Duplication of Chromatin Structure Cohesins Hold Sister Chromatids Together Summary MITOSIS M-Cdk Drives Entry Into Mitosis Dephosphorylation Activates M-Cdk at the Onset of Mitosis Condensin Helps Configure Duplicated Chromosomes for Separation The Mitotic Spindle Is a Microtubule-Based Machine Microtubule-Dependent Motor Proteins Govern Spindle Assembly and Function Multiple Mechanisms Collaborate in the Assembly of a Bipolar Mitotic Spindle Centrosome Duplication Occurs Early in the Cell Cycle M-Cdk Initiates Spindle Assembly in Prophase The Completion of Spindle Assembly in Animal Cells Requires Nuclear-Envelope Breakdown Microtubule Instability Increases Greatly in Mitosis Mitotic Chromosomes Promote Bipolar Spindle Assembly Kinetochores Attach Sister Chromatids to the Spindle Bi-orientation Is Achieved by Trial and Error Multiple Forces Act on Chromosomes in the Spindle The APC/C Triggers Sister-Chromatid Separation and the Completion of Mitosis Unattached Chromosomes Block Sister-Chromatid Separation: The Spindle Assembly Checkpoint Chromosomes Segregate in Anaphase A and B Segregated Chromosomes Are Packaged in Daughter Nuclei at Telophase Summary CYTOKINESIS Actin and Myosin II in the Contractile Ring Generate the Force for Cytokinesis Local Activation of RhoA Triggers Assembly and Contraction of the Contractile Ring The Microtubules of the Mitotic Spindle Determine the Plane of Animal Cell Division The Phragmoplast Guides Cytokinesis in Higher Plants Membrane-Enclosed Organelles Must Be Distributed to Daughter Cells During Cytokinesis Some Cells Reposition Their Spindle to Divide Asymmetrically Mitosis Can Occur Without Cytokinesis The G1 Phase Is a Stable State of Cdk Inactivity Summary MEIOSIS Meiosis Includes Two Rounds of Chromosome Segregation Duplicated Homologs Pair During Meiotic Prophase Homolog Pairing Culminates in the Formation of a Synaptonemal Complex Homolog Segregation Depends on Several Unique Features of Meiosis I Crossing-Over Is Highly Regulated Meiosis Frequently Goes Wrong Summary CONTROL OF CELL DIVISION AND CELL GROWTH Mitogens Stimulate Cell Division Cells Can Enter a Specialized Nondividing State Mitogens Stimulate G1-Cdk and G1/S-Cdk Activities DNA Damage Blocks Cell Division: The DNA Damage Response Many Human Cells Have a Built-In Limitation on the Number of Times They Can Divide Abnormal Proliferation Signals Cause Cell-Cycle Arrest or Apoptosis, Except in Cancer Cells Cell Proliferation is Accompanied by Cell Growth Proliferating Cells Usually Coordinate Their Growth and Division Summary PROBLEMS REFERENCES Chapter 18: Cell Death Apoptosis Eliminates Unwanted Cells Apoptosis Depends on an Intracellular Proteolytic Cascade That Is Mediated by Caspases Cell-Surface Death Receptors Activate the Extrinsic Pathway of Apoptosis The Intrinsic Pathway of Apoptosis Depends on Mitochondria Bcl2 Proteins Regulate the Intrinsic Pathway of Apoptosis IAPs Help Control Caspases Extracellular Survival Factors Inhibit Apoptosis in Various Ways Phagocytes Remove the Apoptotic Cell Either Excessive or Insufficient Apoptosis Can Contribute to Disease Summary PROBLEMS REFERENCES PART V: CELLS IN THEIR SOCIAL CONTEXT Chapter 19: Cell Junctions and the Extracellular Matrix CELL–CELL JUNCTIONS Cadherins Form a Diverse Family of Adhesion Molecules Cadherins Mediate Homophilic Adhesion Cadherin-Dependent Cell–Cell Adhesion Guides the Organization of Developing Tissues Epithelial–Mesenchymal Transitions Depend on Control of Cadherins Catenins Link Classical Cadherins to the Actin Cytoskeleton Adherens Junctions Respond to Forces Generated by the Actin Cytoskeleton Tissue Remodeling Depends on the Coordination of Actin-Mediated Contraction With Cell–Cell Adhesion Desmosomes Give Epithelia Mechanical Strength Tight Junctions Form a Seal Between Cells and a Fence Between Plasma Membrane Domains Tight Junctions Contain Strands of Transmembrane Adhesion Proteins Scaffold Proteins Organize Junctional Protein Complexes Gap Junctions Couple Cells Both Electrically and Metabolically A Gap-Junction Connexon Is Made of Six Transmembrane Connexin Subunits In Plants, Plasmodesmata Perform Many of the Same Functions as Gap Junctions Selectins Mediate Transient Cell–Cell Adhesions in the Bloodstream Members of the Immunoglobulin Superfamily Mediate Ca2+-Independent Cell–Cell Adhesion Summary THE EXTRACELLULAR MATRIX OF ANIMALS The Extracellular Matrix Is Made and Oriented by the Cells Within It Glycosaminoglycan (GAG) Chains Occupy Large Amounts of Space and Form Hydrated Gels Hyaluronan Acts as a Space Filler During Tissue Morphogenesis and Repair Proteoglycans Are Composed of GAG Chains Covalently Linked to a Core Protein Collagens Are the Major Proteins of the Extracellular Matrix Secreted Fibril-Associated Collagens Help Organize the Fibrils Cells Help Organize the Collagen Fibrils They Secrete by Exerting Tension on the Matrix Elastin Gives Tissues Their Elasticity Fibronectin and Other Multidomain Glycoproteins Help Organize the Matrix Fibronectin Binds to Integrins Tension Exerted by Cells Regulates the Assembly of Fibronectin Fibrils The Basal Lamina Is a Specialized Form of Extracellular Matrix Laminin and Type IV Collagen Are Major Components of the Basal Lamina Basal Laminae Have Diverse Functions Cells Have to Be Able to Degrade Matrix, as Well as Make It Matrix Proteoglycans and Glycoproteins Regulate the Activities of Secreted Proteins Summary CELL–MATRIX JUNCTIONS Integrins Are Transmembrane Heterodimers That Link the Extracellular Matrix to the Cytoskeleton Integrin Defects Are Responsible for Many Genetic Diseases Integrins Can Switch Between an Active and an Inactive Conformation Integrins Cluster to Form Strong Adhesions Extracellular Matrix Attachments Act Through Integrins to Control Cell Proliferation and Survival Integrins Recruit Intracellular Signaling Proteins at Sites of Cell–Matrix Adhesion Cell–Matrix Adhesions Respond to Mechanical Forces Summary THE PLANT CELL WALL The Composition of the Cell Wall Depends on the Cell Type The Tensile Strength of the Cell Wall Allows Plant Cells to Develop Turgor Pressure The Primary Cell Wall Is Built from Cellulose Microfibrils Interwoven with a Network of Pectic Polysaccharides Oriented Cell Wall Deposition Controls Plant Cell Growth Microtubules Orient Cell Wall Deposition Summary PROBLEMS REFERENCES Chapter 20: Cancer CANCER AS A MICROEVOLUTIONARY PROCESS Cancer Cells Bypass Normal Proliferation Controls and Colonize Other Tissues Most Cancers Derive from a Single Abnormal Cell Cancer Cells Contain Somatic Mutations A Single Mutation Is Not Enough to Change a Normal Cell into a Cancer Cell Cancers Develop Gradually from Increasingly Aberrant Cells Tumor Progression Involves Successive Rounds of Random Inherited Change Followed by Natural Selection Human Cancer Cells Are Genetically Unstable Cancer Cells Display an Altered Control of Growth Cancer Cells Have an Altered Sugar Metabolism Cancer Cells Have an Abnormal Ability to Survive Stress and DNA Damage Human Cancer Cells Escape a Built-in Limit to Cell Proliferation The Tumor Microenvironment Influences Cancer Development Cancer Cells Must Survive and Proliferate in a Foreign Environment Many Properties Typically Contribute to Cancerous Growth Summary CANCER-CRITICAL GENES: HOW THEY ARE FOUND AND WHAT THEY DO The Identification of Gain-of-Function and Loss-of-Function Cancer Mutations Has Traditionally Required Different Methods Retroviruses Can Act as Vectors for Oncogenes That Alter Cell Behavior Different Searches for Oncogenes Converged on the Same Gene—Ras Genes Mutated in Cancer Can Be Made Overactive in Many Ways Studies of Rare Hereditary Cancer Syndromes First Identified Tumor Suppressor Genes Both Genetic and Epigenetic Mechanisms Can Inactivate Tumor Suppressor Genes Systematic Sequencing of Cancer Cell Genomes Has Transformed Our Understanding of the Disease Many Cancers Have an Extraordinarily Disrupted Genome Many Mutations in Tumor Cells are Merely Passengers About One Percent of the Genes in the Human Genome Are Cancer-Critical Disruptions in a Handful of Key Pathways Are Common to Many Cancers Mutations in the PI3K/Akt/mTOR Pathway Drive Cancer Cells to Grow Mutations in the p53 Pathway Enable Cancer Cells to Survive and Proliferate Despite Stress and DNA Damage Genome Instability Takes Different Forms in Different Cancers Cancers of Specialized Tissues Use Many Different Routes to Target the Common Core Pathways of Cancer Studies Using Mice Help to Define the Functions of Cancer-Critical Genes Cancers Become More and More Heterogeneous as They Progress The Changes in Tumor Cells That Lead to Metastasis Are Still Largely a Mystery A Small Population of Cancer Stem Cells May Maintain Many Tumors The Cancer Stem-Cell Phenomenon Adds to the Difficulty of Curing Cancer Colorectal Cancers Evolve Slowly Via a Succession of Visible Changes A Few Key Genetic Lesions Are Common to a Large Fraction of Colorectal Cancers Some Colorectal Cancers Have Defects in DNA Mismatch Repair The Steps of Tumor Progression Can Often Be Correlated with Specific Mutations Summary CANCER PREVENTION AND TREATMENT: PRESENT AND FUTURE Epidemiology Reveals That Many Cases of Cancer Are Preventable Sensitive Assays Can Detect Those Cancer-Causing Agents that Damage DNA Fifty Percent of Cancers Could Be Prevented by Changes in Lifestyle Viruses and Other Infections Contribute to a Significant Proportion of Human Cancers Cancers of the Uterine Cervix Can Be Prevented by Vaccination Against Human Papillomavirus Infectious Agents Can Cause Cancer in a Variety of Ways The Search for Cancer Cures Is Difficult but Not Hopeless Traditional Therapies Exploit the Genetic Instability and Loss of Cell-Cycle Checkpoint Responses in Cancer Cells New Drugs Can Kill Cancer Cells Selectively by Targeting Specific Mutations PARP Inhibitors Kill Cancer Cells That Have Defects in Brca1 or Brca2 Genes Small Molecules Can Be Designed to Inhibit Specific Oncogenic Proteins Many Cancers May Be Treatable by Enhancing the Immune Response Against the Specific Tumor Cancers Evolve Resistance to Therapies Combination Therapies May Succeed Where Treatments with One Drug at a Time Fail We Now Have the Tools to Devise Combination Therapies Tailored to the Individual Patient Summary PROBLEMS REFERENCES Chapter 21: Development of Multicellular Organisms OVERVIEW OF DEVELOPMENT Conserved Mechanisms Establish the Basic Animal Body Plan The Developmental Potential of Cells Becomes Progressively Restricted Cell Memory Underlies Cell Decision-Making Several Model Organisms Have Been Crucial for Understanding Development Genes Involved in Cell–Cell Communication and Transcriptional Control Are Especially Important for Animal Development Regulatory DNA Seems Largely Responsible for the Differences Between Animal Species Small Numbers of Conserved Cell–Cell Signaling Pathways Coordinate Spatial Patterning Through Combinatorial Control and Cell Memory, Simple Signals Can Generate Complex Patterns Morphogens Are Long-Range Inductive Signals That Exert Graded Effects Lateral Inhibition Can Generate Patterns of Different Cell Types Short-Range Activation and Long-Range Inhibition Can Generate Complex Cellular Patterns Asymmetric Cell Division Can Also Generate Diversity Initial Patterns Are Established in Small Fields of Cells and Refined by Sequential Induction as the Embryo Grows Developmental Biology Provides Insights into Disease and Tissue Maintenance Summary MECHANISMS OF PATTERN FORMATION Different Animals Use Different Mechanisms to Establish Their Primary Axes of Polarization Studies in Drosophila Have Revealed the Genetic Control Mechanisms Underlying Development Egg-Polarity Genes Encode Macromolecules Deposited in the Egg to Organize the Axes of the Early Drosophila Embryo Three Groups of Genes Control Drosophila Segmentation Along the A-P Axis A Hierarchy of Gene Regulatory Interactions Subdivides the Drosophila Embryo Egg-Polarity, Gap, and Pair-Rule Genes Create a Transient Pattern That Is Remembered by Segment-Polarity and Hox Genes Hox Genes Permanently Pattern the A-P Axis Hox Proteins Give Each Segment Its Individuality Hox Genes Are Expressed According to Their Order in the Hox Complex Trithorax and Polycomb Group Proteins Enable the Hox Complexes to Maintain a Permanent Record of Positional Information The D-V Signaling Genes Create a Gradient of the Transcription Regulator Dorsal A Hierarchy of Inductive Interactions Subdivides the Vertebrate Embryo A Competition Between Secreted Signaling Proteins Patterns the Vertebrate Embryo The Insect Dorsoventral Axis Corresponds to the Vertebrate Ventral-Dorsal Axis Hox Genes Control the Vertebrate A-P Axis Some Transcription Regulators Can Activate a Program That Defines a Cell Type or Creates an Entire Organ Notch-Mediated Lateral Inhibition Refines Cellular Spacing Patterns Asymmetric Cell Divisions Make Sister Cells Different Differences in Regulatory DNA Explain Morphological Differences Summary DEVELOPMENTAL TIMING Molecular Lifetimes Play a Critical Part in Developmental Timing A Gene-Expression Oscillator Acts as a Clock to Control Vertebrate Segmentation Intracellular Developmental Programs Can Help Determine the Time-Course of a Cell’s Development Cells Rarely Count Cell Divisions to Time Their Development MicroRNAs Often Regulate Developmental Transitions Hormonal Signals Coordinate the Timing of Developmental Transitions Environmental Cues Determine the Time of Flowering Summary MORPHOGENESIS Cell Migration Is Guided by Cues in the Cell’s Environment The Distribution of Migrant Cells Depends on Survival Factors Changing Patterns of Cell Adhesion Molecules Force Cells Into New Arrangements Repulsive Interactions Help Maintain Tissue Boundaries Groups of Similar Cells Can Perform Dramatic Collective Rearrangements Planar Cell Polarity Helps Orient Cell Structure and Movement in Developing Epithelia Interactions Between an Epithelium and Mesenchyme Generate Branching Tubular Structures An Epithelium Can Bend During Development to Form a Tube or Vesicle Summary GROWTH The Proliferation, Death, and Size of Cells Determine Organism Size Animals and Organs Can Assess and Regulate Total Cell Mass Extracellular Signals Stimulate or Inhibit Growth Summary NEURAL DEVELOPMENT Neurons Are Assigned Different Characters According to the Time and Place of Their Birth The Growth Cone Pilots Axons Along Specific Routes Toward Their Targets A Variety of Extracellular Cues Guide Axons to their Targets The Formation of Orderly Neural Maps Depends on Neuronal Specificity Both Dendrites and Axonal Branches From the Same Neuron Avoid One Another Target Tissues Release Neurotrophic Factors That Control Nerve Cell Growth and Survival Formation of Synapses Depends on Two-Way Communication Between Neurons and Their Target Cells Synaptic Pruning Depends on Electrical Activity and Synaptic Signaling Neurons That Fire Together Wire Together Summary PROBLEMS REFERENCES Chapter 22: Stem Cells and Tissue Renewal STEM CELLS AND RENEWAL IN EPITHELIAL TISSUES The Lining of the Small Intestine Is Continually Renewed Through Cell Proliferation in the Crypts Stem Cells of the Small Intestine Lie at or Near the Base of Each Crypt The Two Daughters of a Stem Cell Face a Choice Wnt Signaling Maintains the Gut Stem-Cell Compartment Stem Cells at the Crypt Base Are Multipotent, Giving Rise to the Full Range of Differentiated Intestinal Cell Types The Two Daughters of a Stem Cell Do Not Always Have to Become Different Paneth Cells Create the Stem-Cell Niche A Single Lgr5-expressing Cell in Culture Can Generate an Entire Organized Crypt-Villus System Ephrin–Eph Signaling Drives Segregation of the Different Gut Cell Types Notch Signaling Controls Gut Cell Diversification and Helps Maintain the Stem-Cell State The Epidermal Stem-Cell System Maintains a Self-Renewing Waterproof Barrier Tissue Renewal That Does Not Depend on Stem Cells: Insulin-Secreting Cells in the Pancreas and Hepatocytes in the Liver Some Tissues Lack Stem Cells and Are Not Renewable Summary FIBROBLASTS AND THEIR TRANSFORMATIONS: THE CONNECTIVE-TISSUE CELL FAMILY Fibroblasts Change Their Character in Response to Chemical and Physical Signals Osteoblasts Make Bone Matrix Bone Is Continually Remodeled by the Cells Within It Osteoclasts Are Controlled by Signals From Osteoblasts Summary GENESIS AND REGENERATION OF SKELETAL MUSCLE Myoblasts Fuse to Form New Skeletal Muscle Fibers Some Myoblasts Persist as Quiescent Stem Cells in the Adult Summary BLOOD VESSELS, LYMPHATICS, AND ENDOTHELIAL CELLS Endothelial Cells Line All Blood Vessels and Lymphatics Endothelial Tip Cells Pioneer Angiogenesis Tissues Requiring a Blood Supply Release VEGF Signals from Endothelial Cells Control Recruitment of Pericytes and Smooth Muscle Cells to Form the Vessel Wall Summary A HIERARCHICAL STEM-CELL SYSTEM: BLOOD CELL FORMATION Red Blood Cells Are All Alike; White Blood Cells Can Be Grouped in Three Main Classes The Production of Each Type of Blood Cell in the Bone Marrow Is Individually Controlled Bone Marrow Contains Multipotent Hematopoietic Stem Cells, Able to Give Rise to All Classes of Blood Cells Commitment Is a Stepwise Process Divisions of Committed Progenitor Cells Amplify the Number of Specialized Blood Cells Stem Cells Depend on Contact Signals From Stromal Cells Factors That Regulate Hematopoiesis Can Be Analyzed in Culture Erythropoiesis Depends on the Hormone Erythropoietin Multiple CSFs Influence Neutrophil and Macrophage Production The Behavior of a Hematopoietic Cell Depends Partly on Chance Regulation of Cell Survival Is as Important as Regulation of Cell Proliferation Summary REGENERATION AND REPAIR Planarian Worms Contain Stem Cells That Can Regenerate a Whole New Body Some Vertebrates Can Regenerate Entire Organs Stem Cells Can Be Used Artificially to Replace Cells That Are Diseased or Lost: Therapy for Blood and Epidermis Neural Stem Cells Can Be Manipulated in Culture and Used to Repopulate the Central Nervous System Summary CELL REPROGRAMMING AND PLURIPOTENT STEM CELLS Nuclei Can Be Reprogrammed by Transplantation into Foreign Cytoplasm Reprogramming of a Transplanted Nucleus Involves Drastic Epigenetic Changes Embryonic Stem (ES) Cells Can Generate Any Part of the Body A Core Set of Transcription Regulators Defines and Maintains the ES Cell State Fibroblasts Can Be Reprogrammed to Create Induced Pluripotent Stem Cells (iPS Cells) Reprogramming Involves a Massive Upheaval of the Gene Control System An Experimental Manipulation of Factors that Modify Chromatin Can Increase Reprogramming Efficiencies ES and iPS Cells Can Be Guided to Generate Specific Adult Cell Types and Even Whole Organs Cells of One Specialized Type Can Be Forced to Transdifferentiate Directly Into Another ES and iPS Cells Are Useful for Drug Discovery and Analysis of Disease Summary PROBLEMS REFERENCES Chapter 23: Pathogens and Infection INTRODUCTION TO PATHOGENS AND THE HUMAN MICROBIOTA The Human Microbiota Is a Complex Ecological System That Is Important for Our Development and Health Pathogens Interact with Their Hosts in Different Ways Pathogens Can Contribute to Cancer, Cardiovascular Disease, and Other Chronic Illnesses Pathogens Can Be Viruses, Bacteria, or Eukaryotes Bacteria Are Diverse and Occupy a Remarkable Variety of Ecological Niches Bacterial Pathogens Carry Specialized Virulence Genes Bacterial Virulence Genes Encode Effector Proteins and Secretion Systems to Deliver Effector Proteins to Host Cells Fungal and Protozoan Parasites Have Complex Life Cycles Involving Multiple Forms All Aspects of Viral Propagation Depend on Host Cell Machinery Summary CELL BIOLOGY OF INFECTION Pathogens Overcome Epithelial Barriers to Infect the Host Pathogens That Colonize an Epithelium Must Overcome Its Protective Mechanisms Extracellular Pathogens Disturb Host Cells Without Entering Them Intracellular Pathogens Have Mechanisms for Both Entering and Leaving Host Cells Viruses Bind to Virus Receptors at the Host Cell Surface Viruses Enter Host Cells by Membrane Fusion, Pore Formation, or Membrane Disruption Bacteria Enter Host Cells by Phagocytosis Intracellular Eukaryotic Parasites Actively Invade Host Cells Some Intracellular Pathogens Escape from the Phagosome into the Cytosol Many Pathogens Alter Membrane Traffic in the Host Cell to Survive and Replicate Viruses and Bacteria Use the Host-Cell Cytoskeleton for Intracellular Movement Viruses Can Take Over the Metabolism of the Host Cell Pathogens Can Evolve Rapidly by Antigenic Variation Error-Prone Replication Dominates Viral Evolution Drug-Resistant Pathogens Are a Growing Problem Summary PROBLEMS REFERENCES Chapter 24: The Innate and Adaptive Immune Systems THE INNATE IMMUNE SYSTEM Epithelial Surfaces Serve as Barriers to Infection Pattern Recognition Receptors (PRRs) Recognize Conserved Features of Pathogens There Are Multiple Classes of PRRs Activated PRRs Trigger an Inflammatory Response at Sites of Infection Phagocytic Cells Seek, Engulf, and Destroy Pathogens Complement Activation Targets Pathogens for Phagocytosis or Lysis Virus-Infected Cells Take Drastic Measures to Prevent Viral Replication Natural Killer Cells Induce Virus-Infected Cells to Kill Themselves Dendritic Cells Provide the Link Between the Innate and Adaptive Immune Systems Summary OVERVIEW OF THE ADAPTIVE IMMUNE SYSTEM B Cells Develop in the Bone Marrow, T Cells in the Thymus Immunological Memory Depends On Both Clonal Expansion and Lymphocyte Differentiation Lymphocytes Continuously Recirculate Through Peripheral Lymphoid Organs Immunological Self-Tolerance Ensures That B and T Cells Do Not Attack Normal Host Cells and Molecules Summary B CELLS AND IMMUNOGLOBULINS B Cells Make Immunoglobulins (Igs) as Both Cell-Surface Antigen Receptors and Secreted Antibodies Mammals Make Five Classes of Igs Ig Light and Heavy Chains Consist of Constant and Variable Regions Ig Genes Are Assembled From Separate Gene Segments During B Cell Development Antigen-Driven Somatic Hypermutation Fine-Tunes Antibody Responses B Cells Can Switch the Class of Ig They Make Summary T CELLS AND MHC PROTEINS T Cell Receptors (TCRs) Are Ig‑like Heterodimers Activated Dendritic Cells Activate Naïve T Cells T Cells Recognize Foreign Peptides Bound to MHC Proteins MHC Proteins Are the Most Polymorphic Human Proteins Known CD4 and CD8 Co-receptors on T Cells Bind to Invariant Parts of MHC Proteins Developing Thymocytes Undergo Negative and Positive Selection Cytotoxic T Cells Induce Infected Target Cells to Kill Themselves Effector Helper T Cells Help Activate Other Cells of the Innate and Adaptive Immune Systems Naïve Helper T Cells Can Differentiate Into Different Types of Effector T Cells Both T and B Cells Require Multiple Extracellular Signals For Activation Many Cell-Surface Proteins Belong to the Ig Superfamily Summary PROBLEMS REFERENCES Glossary Index Tables: The Genetic Code, Amino Acids
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