The 80th Cold Spring Harbor Symposium was held to mark the 150th anniversary of Gregor Mendel’s landmark 1865 presentation of his paper “Experiments on Plant Hybridization”, which laid the groundwork for modern genetics. The Symposium Proceedings addresses 21st Century Genetics: Genes at Work, and provides a current synthesis of genetic mechanisms and genome/chromosome biology. This volume spans a broad range of topics that reflect our current understanding of genetic mechanisms in humans and other organisms. Themes include chromosome biology and nuclear structure, topologically associating domains, gene-enhancer interactions, chromatin and epigenetics, gene regulation and control, developmental regulation, RNA controlling elements, maintenance of genome stability, nuclear receptors, circadian clocks and aging, and genome editing. The Conversations included in this volume are based on interviews conducted during the Symposium and offer a broader anecdotal perspective on this fascinating subject by many of the world’s leading investigators.

The 80th Cold Spring Harbor Symposium was held to mark the 150th anniversary of Gregor Mendel’s landmark 1865 presentation of his paper “Experiments on Plant Hybridization”, which laid the groundwork for modern genetics. The Symposium Proceedings addresses 21st Century Genetics: Genes at Work, and provides a current synthesis of genetic mechanisms and genome/chromosome biology. This volume spans a broad range of topics that reflect our current understanding of genetic mechanisms in humans and other organisms. Themes include chromosome biology and nuclear structure, topologically associating domains, gene-enhancer interactions, chromatin and epigenetics, gene regulation and control, developmental regulation, RNA controlling elements, maintenance of genome stability, nuclear receptors, circadian clocks and aging, and genome editing. The Conversations included in this volume are based on interviews conducted during the Symposium and offer a broader anecdotal perspective on this fascinating subject by many of the world’s leading investigators.

The way we treat cancer is about to change forever. This revolution—and it is precisely that—was sparked not by the invention of a new drug, but by the evolution of an entirely new way of thinking about and managing cancer. Going forward, doctors will not use pharmaceuticals to attack tumors—not directly. Rather, the oncologist will treat the patient's immune system with a drug, and then the patient will treat the tumor.

Based entirely on interviews with the investigators, this book is the story of the immuno-oncology pioneers. It's a story of failure, resurrection, and success. It's a story about science, it's a story about discovery, and intuition, and cunning. It's a peek into the lives and thoughts of some of the most gifted medical scientists on the planet.

This is not a textbook. This is a life book. This technology will save/is saving lives, and the book celebrates the living, breathing, thinking, charming, arrogant, funny, obstinate, amazing human beings who are making immuno-oncology happen.

“The stories and lives shared in this book show readers the decades of devotion and passion it takes to imagine a better world and then make it happen. If this book motivates even one more similarly talented and visionary investigator to deliver on their promise it would be a wonderful success.”

—Clifford A. Hudis, MD, FACP, FASCO

Chief Executive Officer, American Society of Clinical Oncology

Twenty-four true, wide-ranging tales of crime, history, human behavior,
illness, and ethics, told from the personal perspective of the author, an eminent physician-lawyer who uses the stories to illustrate the principles of human genetics and to discuss the broader issues.

About the author: Philip R. Reilly earned his undergraduate degree at Cornell University, studied human genetics at the University of Texas Graduate School of Biomedical Sciences, and graduated from Yale Medical School in 1981. He did his medical residency at Boston City Hospital. He earned board certification in internal medicine and clinical genetics. He has served on the Board of Directors of the American Society of Human Genetics, and he is a Founding Fellow of the American College of Medical Genetics. He twice served as President of the American Society of Law, Medicine, and Ethics. During the 1990s, Reilly was the Executive Director of the Eunice Kennedy Shriver Center for Mental Retardation in Waltham, Massachusetts, a nonprofit that worked on understanding childhood and adult neurological disorders. Dr. Reilly has held faculty positions at Harvard Medical School and Brandeis University. Since 2009 he has worked as a venture partner at Third Rock Ventures in Boston where he focuses on helping to start companies to develop innovative therapies for orphan genetic diseases. Over the years he has published six books and many articles about the impact of advances in genetics. Reilly frequently works with patient groups who are concerned with rare genetic disorders.

Addiction to psychoactive drugs found in cigarettes, alcoholic drinks, and opioid analgesics is a severe problem for society. Events associated with addiction—drug abuse, dependence, withdrawal, and relapse—involve complex neurobiological changes in the brain. To develop effective long-term treatment strategies for substance use disorders, a more complete understanding of these brain changes is needed.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine provides a comprehensive update on our understanding of the biological basis of and treatment strategies for addiction to psychoactive drugs, with an emphasis on opioids. Contributors examine the molecular targets of alcohol, cannabinoids, nicotine, stimulants, and opioids, the resulting changes to the neurocircuitry, and various genetic, environmental, developmental, and behavioral factors that influence the progression from abuse to addiction and susceptibility to relapse. Advances in animal models of addictive behavior and single-cell strategies to dissect neural circuits are also described.

In addition, the authors review compounds currently used or under development to treat substance use disorders, their pharmacological mechanisms, and challenges related to preclinical testing in animal models. This volume is an indispensable reference for all neuroscientists and those who are interested in understanding and reducing the public health burden of drug addiction.

The African turquoise killifish Nothobranchius furzeri is a short-lived fish species that has been established as a novel vertebrate model to study aging and represents a promising system to examine various other processes. The killifish is relatively easy and inexpensive to maintain. In addition, it has a short life cycle and abundant progeny, facilitating its use. Investigation using this model organism is growing and has provided new insights into aging, age-related diseases, ecology, evolution, and embryonic diapause—a state of “suspended animation.”

This laboratory manual provides a comprehensive collection of protocols covering experimental techniques currently used to study the African turquoise killifish. Husbandry protocols describe how to set up and maintain a killifish colony and how to generate and preserve genetically engineered killifish lines. This collection also includes both general and specific methods to characterize different organs during aging, with a particular focus on the brain. Several genomics methods and analyses for unbiased characterization are also described. Finally, this manual encompasses protocols in other interesting areas of research, including injury repair, development, and embryonic diapause.

This collection should enable studies in the African turquoise killifish and other species of killifish such as the South American killifish, and includes protocols that will be useful both to groups considering the use of these systems for the first time and to those with experience in the field. We also hope that this protocol book will foster a large killifish community and will promote new studies in many different research areas.

The author is the Novartis Professor of Biology at the Massachusetts Institute of Technology.

Aging has always been regarded as a highly complex process with many degenerative changes leading to the cessation of life. But recent research has identified a relatively simple mechanism that governs the pace of aging.

Lenny Guarente's Ageless Quest is a scientific detective story for the baby boom generation. It offers an insider's view of an area of potentially astonishing high reward—and equally high risk.

To read Lenny Guarente's and Robert Butler's interview with Sara Davidson (The NY Times) about how the body ages and the research on trying to extend our healthy life span, click here. (You must register for free access to NYTimes.com)

Aging represents a growing challenge for modern human populations, but in many ways our longer lives also represent an opportunity. People are living longer, but diseases associated with aging place an enormous burden on health systems, caregivers, and wider society. It is critical to elucidate the fundamental biology involved so that we can develop treatments for aging itself in addition to the fatal and disabling diseases and disorders associated with it. We must also understand the socioeconomic effects of life span and health span extension and adapt institutions accordingly.

Written and edited by experts in the field, this new volume from Cold Spring Harbor Perspectives in Medicine examines recent progress in our understanding of the biology of aging, strategies that may extend health span, and the societal implications. The contributors examine the underlying molecular mechanisms that lead to aging and consider the process from an evolutionary perspective. They also explore how life span may be extended, resistance to aging-associated conditions such as Alzheimer’s disease may be enhanced, and how society would benefit from increased health span.

In addition, the authors discuss funding mechanisms for aging research and the way in which the field should develop as a discipline. This volume is thus an important reference for scientists and clinicians involved in geroscience and geriatric medicine, as well as those interested in the broader policy picture.

Aging is one of the greatest challenges currently facing society. People are living longer than ever, but many of the later years are fraught with frailty and disease, placing an enormous burden on health-care systems. Understanding the biological changes that occur during aging and developing strategies to address them are therefore urgently needed.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the biological basis of aging, strategies that may extend health span, and the societal implications of delayed aging. Contributors discuss genetic variants that accelerate or protect against aging, biochemical pathways that modulate longevity (e.g., mTOR), biological consequences of aging (e.g., decline in stem cell function), and various animal models used to study aging processes. They emphasize that age-delaying interventions will yield greater health and vitality than disease-specific treatments. Drugs that may promote health span or longevity (e.g., metformin) and efforts to prevent and treat frailty (e.g., through exercise) are explored.

The authors consider the socioeconomic benefits and costs of delayed aging and also outline directions for future research and translational efforts. This volume will serve as a vital reference for all involved in the fields of geroscience and geriatric medicine, as well as anyone wishing to understand physiological processes that generate health and disease, regardless of chronological age.

The MRC Laboratory of Molecular Biology (LMB) in Cambridge, UK is a world-leading scientific institution. This book, by LMB alumna Kathy Weston, is a collective portrait of women scientists who, as staff members, visitors, and trainees, helped build the LMB’s reputation as a powerhouse of science, often going on to stellar careers at other outstanding institutions around the world. Combining narrative history with interview transcripts and personal reminiscence, Weston’s book describes the career accomplishments of these successful scientists in the context of their lives as a whole, and how they manage goals and priorities, particularly around personal and family lives. The book provides future sisters in science with role models and inspiration but is recommended reading for everyone intent on combining success in research with a satisfying life outside science.

New blood vessels arise through a process known as angiogenesis, in which endothelial cells proliferate and sprout to form new vessels. Angiogenesis is vital for embryonic development, patterning of the vascular system, and wound healing. Vascular dysfunction contributes to a host of pathological conditions, including cardiovascular diseases, metabolic syndrome, obesity, and lymphedema.

Written and edited by experts in the field, this new collection from Cold Spring Harbor Perspectives in Medicine provides an overview of recent progress in our understanding of the causal mechanisms essential for angiogenesis and lymphangiogenesis in normal physiology and disease. The contributors review how the behavior of endothelial cells is controlled and discuss the regulatory roles of signaling molecules such as vascular endothelial growth factor, Notch, Wnt, VE-cadherin, and epsins. Vascular inflammation, immune cell trafficking, lipid metabolism, microRNAs, and the microbiome are also covered in the context of homeostasis and vasculature-related pathological conditions.

Including discussions of vascular permeability and lymphatic drainage as well as interactions between the vascular system and smooth muscle cells, the blood–brain barrier, and the immune system, this volume is a vital reference for developmental and vascular biologists as well as anyone seeking to understand the biology and pathology underlying vasculature-dependent diseases.

The structure of DNA deduced by James Watson and Francis Crick in 1953 was one of the most significant scientific discoveries of the 20th century. Fifteen years later, Watson wrote The Double Helix, his classic account of the discovery. It was something new, a description of science in action written not as a formal autobiography or a measured history, but in the voice of a brash, ambitious young man who knew the big question in biology and wanted the answer.

In this edition, Watson’s text is unchanged, but Alex Gann and Jan Witkowski have added over three hundred annotations on the events and characters portrayed, with facsimile letters and contemporary photographs, many previously unpublished. Their sources include newly discovered correspondence from Crick, the papers of Franklin, Pauling, and Wilkins, and they include a chapter dropped from the original edition.

The Double Helix is recognized by the Library of Congress as “A Book That Shaped America”. This new edition, published to mark the 50th anniversary of the Nobel Prize for Watson, Crick, and Wilkins, and the 60th anniversary of the discovery itself, adds depth and richness to one of the most famous stories in science.

“The Double Helix is the best book I know about a scientific discovery—this new edition suffuses the whole with social history, fascinating documentation, photography, and cunning background research. The early fifties, the beginning of the modern age of molecular biology, spring to life.“ ——Ian McEwan, author of Atonement

“The Double Helix is an extraordinary book: a thrilling, novelistic account of one of the most surprising of all scientific discoveries. This new edition draws upon a remarkable and eclectic archive of information to bring to life the stories of those who found the secret of life.“ — Matt Ridley, author of Genome and Francis Crick

One of the greatest medical accomplishments of the past century was the introduction of antibiotics into the clinic. However, the use of these lifesaving drugs rapidly led to the emergence of antibiotic-resistant pathogens, which have become increasingly difficult and expensive to eradicate. Antibiotic resistance now severely limits our ability to curb infectious diseases and is therefore a major global health concern.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the major classes of antibiotics, together with their modes of action and mechanisms of resistance. Well-established antibiotics (e.g., β-lactams) are covered, as are lesser-used drugs that have garnered recent interest (e.g., polymyxins) and new compounds in the development pipeline. The contributors describe the mechanisms by which the agents disrupt cell wall assembly and maintenance, membrane synthesis and integrity, DNA and RNA metabolism, protein synthesis, and the folate cycle. They also examine how bacteria evolve ways to resist these disruptions by modifying the drug or drug target or by controlling access of the drug to the cell.

The authors also explore the environmental origins of antibiotic resistance and provide guidance on the rational development and therapeutic application of new antibiotics. This volume is therefore an essential reference for microbiologists, pharmacologists, infectious disease biologists, and all concerned with this medical crisis.

• antibody purification and storage
  
• engineering antibodies, including use of degenerate oligonucleotides, 5'-RACE, phage display, and mutagenesis
  
• extensive labeling techniques
  
• new immunoblotting protocols
  
• the latest screening and labeling techniques
  

What's New in This Edition?

I have the first edition. Why should I buy the second edition?

While the core of the first edition appears in updated and recast form in the second edition, more than half of the second edition contains entirely new information and protocols to reflect the changes in the field since the first edition.

To whom is this edition addressed? Is this a book for immunologists?

As with the first edition, the second edition provides information and protocols for both the neophyte and the experienced investigator. It dissects the mysteries of producing the antibodies and reagents you need for your experiments with the needs of molecular biologists in mind. It is the perfect book for new members of your lab as it has sufficient background information to provide context as well as clear, step-by-step instructions for performing the needed experiments—both the why and the how for these techniques. And if things go wrong, there is extensive troubleshooting to diagnose the problem.

Are the protocols in this book better than those available for download on the Web?

Many of the protocols available on the Web are perfectly good, but there are many that are not. Reagents are expensive and deadlines are tight. CSHL Press manuals provide protocols that have been formulated and tested in the labs of leading investigators in the field. They are reliable and they work. And they include the context and troubleshooting information that many online protocols do not have.

At the Bench is the unique and hugely successful handbook for living and working in the laboratory, an essential aid to understanding basic lab techniques and how research groups work at a human level. In this newly revised edition, chapters have been rewritten to accommodate the impact of computer technology and the Internet, not only on the acquisition and analysis of data, but also on its organization and presentation. Alternatives to the use of radiation have been expanded, and figures and illustrations have been redrawn to reflect changes in laboratory equipment and procedures.

Wise, light-hearted, but thoroughly practical, Dr. Barker offers advice, moral support, social etiquette, and professional reassurance along with assume-nothing, step-by-step instructions for those basic but vital laboratory procedures that experienced investigators know—but may not realize novices don’t.

If you are a graduate student, a physician with research intentions, or a laboratory technician, this book is indispensable. If you have to manage or mentor such people, giving a copy to each of them will greatly improve your life, and theirs.

About the author: Kathy Barker received her B.A. in Biology and English, and her M.A. and Ph.D. in Microbiology, from various branches of the University of Massachusetts. She did her postdoctoral work in the laboratory of Viral Oncology at Rockefeller University and was an Assistant Professor in the Laboratory of Cell Physiology and Immunology at Rockefeller University. She is now based in Seattle, where she writes and gives workshops on various aspects of running a lab.

Dr. Barker invites you to send any comments or questions to her.

About the author: Kathy Barker received her B.A. in Biology and English, and her M.A. and Ph.D. in Microbiology, from various branches of the University of Massachusetts. She did her postdoctoral work in the laboratory of Viral Oncology at Rockefeller University and was an Assistant Professor in the Laboratory of Cell Physiology and Immunology at Rockefeller University. She is now based in Seattle, where she writes and gives workshops on various aspects of running a lab.

Dr. Barker invites you to send any comments or questions to her.

Auxin is a hormone that plays a central role in plant growth, tissue patterning, organogenesis, and responses to light. Differences in auxin concentrations in different regions of the plant result in dramatic changes in gene expression, up- or down-regulating distinct sets of target genes. Recent technological advances have provided insights into mechanistic details of auxin signaling and its many roles in plant biology.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers recent insights into how auxin levels are regulated and, in turn, drive various developmental processes in plants. The contributors discuss the biosynthesis, conjugation, and degradation of auxin, the various transporters, receptors, and transcription factors involved in auxin signaling, the interactions of auxin with other plant hormones, and how these are spatiotemporally coordinated. The roles of auxin in specific organs and tissues—the shoot apical meristem, roots, vasculature, and flowers—are described in detail. The evolutionary history of auxin signaling and its roles in environmental responses (e.g., plant-pathogen interactions) are also reviewed.

Other topics include the development of computational models for root and shoot growth, as well as chemical tools and synthetic systems to understand auxin biology. This volume is therefore an essential reference for all plant biologists, as well as systems biologists, biochemists, and developmental biologists interested in the regulation of plant morphogenesis and behavior.

Bacterial illnesses—such as tuberculosis, pneumonia, typhoid fever, meningitis, and dysentery—are some of the most devastating worldwide. Although antibiotics and vaccines control their prevalence to some extent, the emergence of new virulence mechanisms and new forms of resistance to antibacterial agents makes research in this field critical to understanding and controlling infectious diseases.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine provides a comprehensive review of the biology of these pathogens, their virulence mechanisms, and the host's response to infection. The contributors survey the various toxins and effectors that are used to hijack the cellular machinery of the host, and they explain how their production is coordinated and controlled. The host specificity of bacterial pathogens and the genetic basis of susceptibility are also considered. Other chapters are devoted to the pathogenic mechanisms of specific bacterial species (e.g., Salmonella, Chlamydia, and Helicobacter pylori).

The authors also describe novel vaccine strategies and antimicrobial approaches (e.g., phage therapy or biofilm disruption), as well as the use of probiotics to benefit human health. This volume is thus an essential reference for microbiologists, immunologists, and cell and molecular biologists, as well as clinicians and other public health professionals.

Basic Methods in Microscopy provides an essential guide to light microscopy, fluorescence microscopy, confocal microscopy, multiphoton microscopy and electron microscopy, preparation of tissues and cells, labeling of specimens and analysis of cellular events.

This manual is an important tool for any biology researcher employing imaging as a research method.

The collection of essential methods found in Basic Methods in Protein Purification and Analysis is mainly drawn from the popular manuals Proteins and Proteomics, Purifying Proteins for Proteomics, and Protein–Protein Interactions, 2nd Ed. In addition to protocols for purification using gel electrophoresis and column chromatography, this book contains tested methods for preparing cellular and subcellular extracts–a critical and often neglected step in successful protein purification. Rounding out the manual are methods for characterizing protein–protein interactions, an extensive appendix of essential methods for quantifying protein concentration, stabilizing and storing proteins, concentrating proteins, and immunoblotting. Finally, there is a new chapter on a method complementary to gel electrophoresis and chromatography: in silico analysis of genomic and proteomic databases.

Stereological techniques allow biologists to create quantitative, three-dimensional descriptions of biological structures from two-dimensional images of tissue viewed under the microscope. For example, they can accurately estimate the size of a particular organelle, the total length of a mass of capillaries, or the number of neurons or synapses in a particular region of the brain.

This book provides a practical guide to designing and critically evaluating stereological studies of the nervous system and other tissues. It explains the basic concepts behind design-based stereology and how to get started. Also included are detailed descriptions of how to prepare tissue appropriately, perform pilot studies and decide on the appropriate sampling strategy, and account for phenomena such as tissue shrinkage. Numerous examples of applications of stereological methods that are applicable to studies of the central system and a wide variety of other tissues are explained. The book is therefore essential reading for neurobiologists and cell biologists interested in generating accurate representations of cell and tissue architecture.

Every organ in the human body is innervated by the nervous system and communicates with the brain via electrical signals. Various devices can be used to modulate these electrical signals and elicit changes in organ function with the aim of treating injury or disease. This approach is the basis of the rapidly emerging field of bioelectronic medicine, which has the potential to diagnose and treat medical conditions more precisely and effectively than ever before.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers many aspects of bioelectronic medicine, examining the neuronal pathways that are being targeted for manipulation, the electronic neuromodulation devices that are under development, and how all of this work is leading to new diagnostics and treatment options for patients. The contributors discuss how the stimulation of specific nerves (e.g., the vagus nerve) has been successfully used to treat certain conditions (e.g., rheumatoid arthritis and Crohn’s disease) and how similar strategies are being investigated as therapeutics for a multitude of gastrointestinal, cardiovascular, respiratory, and renal disorders. They consider implantable devices, magnetoelectric nanoparticles, ultrasound, optogenetic-based approaches, and electrophotonic devices as tools for acquiring, decoding, and modulating electrical signals from nerves and how they might be used to monitor and treat patients in the clinic.

The authors also discuss the ethical concerns related to the use of technologies such as these that can alter the brain. The volume is therefore an indispensable reference for neuroscientists, biomedical engineers, and physicians interested in the benefits and challenges of recording, stimulating, and blocking electrical activity in the human body.

Informatics can vastly assist progress in research and development in cell and molecular biology and biomedicine. However, many investigators are either unaware of the ways in which informatics can improve their research or find it inaccessible due to a feeling of “informatics anxiety.” This sense of apprehension results from improper communication of the principles behind these approaches and of the value of the many tools available. In fact, many researchers are inherently distrustful of these tools. A more complete understanding of bioinformatics offered in A Bioinformatics Guide for Molecular Biologists will allow the reader to become comfortable with these techniques, encouraging their use—thus helping to make sense of the vast accumulation of data. To make these concepts more accessible, the editors approach the field of bioinformatics from the viewpoint of a molecular biologist, (1) arming the biologist with a basic understanding of the fundamental concepts in the field, (2) presenting approaches for using the tools from the standpoint of the data for which they are created, and (3) showing how the field of informatics is quickly adapting to the advancements in biology and biomedical technologies. All concepts are paired with recommendations for the appropriate programming environment and tools best suited to solve the particular problem at hand. It is a must-read for those interested in learning informatics techniques required for successful research and development in the laboratory.

As more species' genomes are sequenced, computational analysis of these data has become increasingly important. The second, entirely updated edition of this widely praised textbook provides a comprehensive and critical examination of the computational methods needed for analyzing DNA, RNA, and protein data, as well as genomes. The book has been rewritten to make it more accessible to a wider audience, including advanced undergraduate and graduate students. New features include chapter guides and explanatory information panels and glossary terms. New chapters in this second edition cover statistical analysis of sequence alignments, computer programming for bioinformatics, and data management and mining. Practically oriented problems at the ends of chapters enhance the value of the book as a teaching resource. The book also serves as an essential reference for professionals in molecular biology, pharmaceutical, and genome laboratories.

Alzheimer disease causes the gradual deterioration of cognitive function, including severe memory loss and impairments in abstraction and reasoning. Understanding the complex changes that occur in the brain as the disease progresses—including the accumulation of amyloid plaques and neurofibrillary tangles—is critical for the development of successful therapeutic approaches.

Written and edited by leading experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine includes contributions covering all aspects of Alzheimer disease, from our current molecular understanding to therapeutic agents that could be used to treat and, ultimately, prevent it. Contributors discuss the biochemistry and cell biology of amyloid β-protein precursor (APP), tau, presenilin, β-secretase, and apolipoprotein E and their involvement in Alzheimer disease. They also review the clinical, neuropathological, imaging, and biomarker phenotypes of the disease; genetic alterations associated with the disorder; and epidemiological insights into its causation and pathogenesis.

This comprehensive volume, which includes discussions of therapeutic strategies that are currently used or under development, is a vital reference for neurobiologists, cell biologists, pathologists, and other scientists pursuing the biological basis of Alzheimer disease, as well as investigators, clinicians, and students interested in its pathogenesis, treatment, and prevention.

Biology of Drosophila was first published by John Wiley and Sons in 1950. Until its appearance, no central, synthesized source of biological data on Drosophila melanogaster was available, despite the fly's importance to science for three decades. Ten years in the making, it was an immediate success and remained in print for two decades. However, original copies are now very hard to find. This facsimile edition makes available to the fly community once again its most enduring work of reference.

Exercise training provokes widespread transformations in the human body, requiring coordinated changes in muscle composition, blood flow, neuronal and hormonal signaling, and metabolism. These changes enhance physical performance, improve mental health, and delay the onset of aging and disease. Understanding the molecular basis of these changes is therefore important for optimizing athletic ability and for developing drugs that elicit therapeutic effects.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the biological basis of exercise from the molecular to the systemic levels. Contributors discuss how transcriptional regulation, cytokine and hormonal signaling, glucose metabolism, epigenetic modifications, microRNA profiles, and mitochondrial and ribosomal functions are altered in response to exercise training, leading to improved skeletal muscle, hippocampal, and cardiovascular functions. Cross talk among the pathways underlying tissue-specific and systemic responses to exercise is also considered.

The authors also discuss how the understanding of such molecular mechanisms may lead to the development of drugs that mitigate aging and disease. This volume will therefore serve as a vital reference for all involved in the fields of sports science and medicine, as well as anyone seeking to understand the molecular mechanisms by which exercise promotes whole-body health.

The heart is the first organ to form in a developing embryo, and all subsequent life processes depend on its proper function. But a range of genetic and environmental factors can lead to its failure. Inherited mutations give rise to congenital heart disease, the most common birth defect, and abnormalities of the adult heart are a leading cause of illness and death in industrialized countries.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine describes how recent advances in genetics, stem cell biology, and developmental biology are transforming the way we understand and treat heart disease. Contributors review the various cell lineages and molecular networks involved in heart development; the genetic basis of inherited cardiac conditions such as congenital heart disease, cardiomyopathies, and aortic aneurysm; and how various cutting-edge technologies and models are being employed to study heart biology, uncover disease-related processes, and identify therapeutic targets. Topics include tissue engineering, genome editing, stem cells, cardiomyocyte reprogramming, chemically modified RNA, and next-generation DNA sequencing.

The authors also consider the process of drug discovery and development, and the potential for patient-specific treatments and therapies. This volume is a valuable reference for cardiologists, geneticists, and cell and developmental biologists interested in this complex, vital organ and the future of cardiovascular medicine.

Lipids are the major component of cell and organelle membranes. They are essential for maintaining cell integrity and defining distinct subcellular compartments but also play important roles in a variety of other cellular processes. Membrane fission and fusion and movement of lipid-enveloped vesicles underlie the majority of protein trafficking in cells and are critical for the function of synapses in the nervous system. In addition, lipids participate in numerous signaling pathways that connect cell-surface receptors with intracellular effectors.

Written and edited by experts in the field, this new edition of the highly successful Cold Spring Harbor volume on lipids provides a comprehensive update on lipid cell biology. The contributors discuss the organization of lipids in cellular membranes, membrane biophysics, and the phase transitions lipids undergo. They examine tools for analysis of lipids and lipid modifications. They also review our understanding of lipid sorting and its role in maintenance of organelle identity.

The volume covers the functions of lipids in various signal transduction pathways, as well as the roles of cholesterol, extracellular vesicles, and the importance of lipids in the unfolded protein response. Including discussion of the importance of lipids for synaptic activity and memory, it is an indispensable reference not only for cell biologists and biochemists but neurobiologists and any other researchers interested in the importance of lipids in cell physiology.

Plants are integral to human well being, and many species have been domesticated for over ten thousand years. Evidence of plant scientific investigation and classification can be found in ancient texts from cultures around the world (Chinese, Indian, Greco-Roman, Muslim etc.), while early modern botany can be traced to the late 15th and early 16th centuries in Europe. During the past several decades plant biology has been revolutionized first by molecular biology and then by the genomic era. The model organism Arabidopsis thaliana has proved an invaluable tool for investigation into fundamental processes in plant biology, many of which share commonalities with animal biology. Plant-specific processes from reproduction to immunity and second messengers have also yielded to extensive investigation. With the genomes of more than thirty plant species now available and many more planned in the near future, the impact on our understanding of plant evolution and biology continues to grow. Our increased ability to engineer plant species to a variety of ends may provide novel solutions to ensure adequate and reliable food production and renewable energy even as climate change impacts our environment. The decision to focus the 2012 Symposium on plant science reflects the enormous research progress achieved in recent years, and is intended to provide a broad synthesis of the current state of the field, setting the stage for future discoveries and application. This is the first Symposium in this historic series focused exclusively on the botanical sciences.

Plants are integral to human well being, and many species have been domesticated for over ten thousand years. Evidence of plant scientific investigation and classification can be found in ancient texts from cultures around the world (Chinese, Indian, Greco-Roman, Muslim etc.), while early modern botany can be traced to the late 15th and early 16th centuries in Europe. During the past several decades plant biology has been revolutionized first by molecular biology and then by the genomic era. The model organism Arabidopsis thaliana has proved an invaluable tool for investigation into fundamental processes in plant biology, many of which share commonalities with animal biology. Plant-specific processes from reproduction to immunity and second messengers have also yielded to extensive investigation. With the genomes of more than thirty plant species now available and many more planned in the near future, the impact on our understanding of plant evolution and biology continues to grow. Our increased ability to engineer plant species to a variety of ends may provide novel solutions to ensure adequate and reliable food production and renewable energy even as climate change impacts our environment. The decision to focus the 2012 Symposium on plant science reflects the enormous research progress achieved in recent years, and is intended to provide a broad synthesis of the current state of the field, setting the stage for future discoveries and application. This is the first Symposium in this historic series focused exclusively on the botanical sciences.

The transforming growth factor β (TGF-β) family is a large group of structurally related proteins that drive developmental programs and control cell behavior. The TGF-β family members exert their effects by binding to receptors on the cell surface, activating intracellular signaling pathways that modulate gene expression programs that control normal cell physiology, immune responses, and a variety of developmental processes. TGF-β signaling is also important in conditions such as cancer, skeletal disorders, and cardiovascular diseases.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive view of the different members of the TGF-β family, the signaling pathways they control, and how they influence development, normal physiology, and disease. The contributors describe the various TGF-β family ligands, including activins and bone morphogenetic proteins (BMPs), the structures and functions of the type I and type II receptors, and how ligand-receptor binding is regulated. Both Smad and non-Smad signaling pathways are discussed, as is cross talk between TGF-β and other signaling pathways (e.g., Wnt). Individual chapters are devoted to the roles of TGF-β signaling in specific biological processes, including cell proliferation, mesenchymal differentiation, branching morphogenesis, stem cell biology, immunity, vascular function, reproduction, and neurobiology. The roles of TGF-β signaling in cancer, fibrosis, skeletal diseases, and other conditions, as well as prospects for therapeutics, are also covered.

The authors also review TGF-β signaling in model organisms (e.g., C. elegans and Drosophila), as well as the discovery of TGF-β and early research in the field. This volume is therefore a comprehensive reference on the biology of the TGF-β family, and it will be valuable for not only cell and developmental biologists but all who wish to learn about this important field of research.

What happens when a cancer research institute's only remit is to be the best it can be? For more than 100 years, one laboratory in London has operated on just that premise. With a generous budget, inspired leadership, and a stable of scientific thoroughbreds, the Imperial Cancer Research Fund Laboratories produced some of the 20th century's most exciting advances in molecular biology. In its 21st century incarnation, as the Cancer Research UK London Research Institute, it continues to inspire a new generation of researchers.

In this book, written with the assistance of the past and present inhabitants of the London Research Institute, Kathy Weston tells the inside story of the lab's greatest voyages into the scientific unknown, revealing the personalities behind the dry passive voice of the scientific paper. Science is an art, a vocation, a complicated landscape of data in which, just sometimes, the trained and alert eye can detect a glint of gold. In these pages, the gold is present, but equally to be treasured are the all-too-human scientists stumbling towards its seductive glimmer.

Bone plays far more than just a structural role in our bodies. It actively communicates with our brains, kidneys, and other organs, releasing and responding to signaling molecules that regulate biological processes such as glucose metabolism and lymphoid development. Defects in these interactions may lead to osteoporosis, multiple myeloma, and other diseases or developmental flaws.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines our current understanding of the dynamic interactions between bone and other organs and systems in the body and the molecules and mechanisms that mediate them. Contributors discuss endocrine factors that act on bone (e.g., parathyroid hormone and sex steroids) as well as molecules that are secreted by bone and act on other tissues (e.g., osteocalcin and FGF23). The interplay between bone and the nervous, immune, and vascular systems is explored, as is the influence of gut microbiota on bone homeostasis.

The authors also consider the diseases that result when homeostatic pathways are disrupted and how new knowledge of these pathways may be harnessed for the development of therapeutics. This volume is therefore a valuable reference for not only physiologists and endocrinologists but for all who are interested in diseases linked to the skeletal system.

Breast cancer is diagnosed in over two million people each year and kills more than six hundred thousand. It has numerous histological subtypes, each with different molecular properties, and a variety of genetic and environmental factors increase an individual’s risk of developing the disease.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine reviews our understanding of breast cancer epidemiology, the molecular and cellular mechanisms underlying its progression, and recent advances in tumor prevention, detection and treatment. The contributors discuss how work using animal models, patient-derived xenografts, and organoid cultures, together with new imaging approaches, is providing new insights into the molecular pathology of breast cancer. In addition, they examine genetic and genomic determinants, the role of chromatin, and research into intra- and inter-tumor heterogeneity.

The authors also discuss tumor dormancy, the importance of the immune system in breast cancer, and ways this may be harnessed in tumor immunotherapy. This volume is therefore a vital reference for all biologists seeking to understand the biological basis of cancer, as well as immunologists and oncologists dedicated to combating this deadly disease.

Over the past century, studies of the budding yeast Saccharomyces cerevisiae have helped to unravel principles of nearly every aspect of eukaryotic cell biology—from metabolism and molecular genetics to cell division and differentiation. Thanks to its short generation time, ease of genetic manipulation, and suitability for high-throughput studies, yeast remains the focus of research in a vast number of laboratories worldwide.

This laboratory manual provides a comprehensive collection of experimental procedures that continue to make budding yeast an informative model. The contributors describe methods for culturing and genetically modifying yeast, strategies and tools (e.g., gene deletion collections) for functional analyses, approaches for characterizing cell structure and morphology, and techniques to probe the modifications and interactions of various cellular constituents (e.g., using one- and two-hybrid screens). Strategies for studying metabolomics, complex traits, and evolution in yeast are also covered, as are methods to isolate and investigate new strains of yeast from the wild.

Several additional chapters are devoted to bioinformatics tools and resources for yeast biology (e.g., the Saccharomyces Genome Database). This manual is therefore an essential resource for all researchers, from graduate level upward, who use budding yeast to explore the intricate workings of cells.

Over the past century, studies of the budding yeast Saccharomyces cerevisiae have helped to unravel principles of nearly every aspect of eukaryotic cell biology—from metabolism and molecular genetics to cell division and differentiation. Thanks to its short generation time, ease of genetic manipulation, and suitability for high-throughput studies, yeast remains the focus of research in a vast number of laboratories worldwide.

This laboratory manual provides a comprehensive collection of experimental procedures that continue to make budding yeast an informative model. The contributors describe methods for culturing and genetically modifying yeast, strategies and tools (e.g., gene deletion collections) for functional analyses, approaches for characterizing cell structure and morphology, and techniques to probe the modifications and interactions of various cellular constituents (e.g., using one- and two-hybrid screens). Strategies for studying metabolomics, complex traits, and evolution in yeast are also covered, as are methods to isolate and investigate new strains of yeast from the wild.

Several additional chapters are devoted to bioinformatics tools and resources for yeast biology (e.g., the Saccharomyces Genome Database). This manual is therefore an essential resource for all researchers, from graduate level upward, who use budding yeast to explore the intricate workings of cells.

Calcium signals—rapid changes in calcium ion concentration—are carefully orchestrated by a suite of proteins that transport and bind to calcium ions inside cells. These signals influence virtually all aspects of animal development and physiology, from fertilization and cell differentiation to muscle contraction and nerve impulses. Aberrant calcium signaling is associated with various pathologies (e.g., cancer and neurodegeneration) as well as aging.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive update on major facets of calcium signaling. The contributors discuss the components and activities of the various calcium-sequestering organelles inside cells, the dynamic interactions that lead to spatiotemporally distinct signals in different circumstances, and the downstream effector mechanisms that translate the signals into biological outcomes. Recent advances in the field (e.g., structural insights into the functions of certain calcium channels) are emphasized throughout.

The authors also discuss normal and perturbed calcium signaling during fertilization, development, physiology, regeneration, aging, and disease. This volume is therefore an indispensable reference for biochemists, cell and developmental biologists, and physiologists seeking a comprehensive treatment of calcium signaling.

Life begins with a surge of calcium ions (Ca²⁺) at fertilization, and thereafter, Ca²⁺ signaling influences nearly every aspect of mammalian development and physiology, from gene expression and cell proliferation to muscle contraction and nerve impulses. To create spatiotemporally distinct Ca²⁺ signals, cells use a variety of mechanisms to recognize, transport, and buffer Ca²⁺. Thus, a diverse range of reliable experimental techniques is necessary to study the movement of Ca²⁺ and the various effectors involved.

This laboratory manual provides step-by-step protocols for studying many facets of Ca²⁺ signaling, as well as background information on the principles and applications of the techniques. Contributors discuss how to use fluorescent, luminescent, and genetically encoded Ca²⁺ probes in conjunction with state-of-the-art imaging modalities to characterize Ca²⁺ signals. Electrophysiological measurements of Ca²⁺ channel activity are described, as are radioactive Ca²⁺ flux assays and methods to investigate signaling mediated by specific Ca²⁺-mobilizing messengers (IP₃, cADPR, and NAADP). Techniques to modulate and suppress intra- and intercellular signals are also provided. Each protocol is complete with a list of required materials, detailed recipes for media and reagents, and troubleshooting advice.

Specific chapters are devoted to Ca²⁺ signaling techniques in nonmammalian systems, such as plants, yeast, zebrafish, and Xenopus. Methods for assessing Ca²⁺-binding kinetics and strategies for developing mathematical models of Ca²⁺ signaling are also included. Thus, this manual is a comprehensive laboratory resource for biochemists, cell and developmental biologists, and physiologists who are using or looking to expand their repertoire of Ca²⁺ techniques.

Life begins with a surge of calcium ions (Ca²⁺) at fertilization, and thereafter, Ca²⁺ signaling influences nearly every aspect of mammalian development and physiology, from gene expression and cell proliferation to muscle contraction and nerve impulses. To create spatiotemporally distinct Ca²⁺ signals, cells use a variety of mechanisms to recognize, transport, and buffer Ca²⁺. Thus, a diverse range of reliable experimental techniques is necessary to study the movement of Ca²⁺ and the various effectors involved.

This laboratory manual provides step-by-step protocols for studying many facets of Ca²⁺ signaling, as well as background information on the principles and applications of the techniques. Contributors discuss how to use fluorescent, luminescent, and genetically encoded Ca²⁺ probes in conjunction with state-of-the-art imaging modalities to characterize Ca²⁺ signals. Electrophysiological measurements of Ca²⁺ channel activity are described, as are radioactive Ca²⁺ flux assays and methods to investigate signaling mediated by specific Ca²⁺-mobilizing messengers (IP₃, cADPR, and NAADP). Techniques to modulate and suppress intra- and intercellular signals are also provided. Each protocol is complete with a list of required materials, detailed recipes for media and reagents, and troubleshooting advice.

Specific chapters are devoted to Ca²⁺ signaling techniques in nonmammalian systems, such as plants, yeast, zebrafish, and Xenopus. Methods for assessing Ca²⁺-binding kinetics and strategies for developing mathematical models of Ca²⁺ signaling are also included. Thus, this manual is a comprehensive laboratory resource for biochemists, cell and developmental biologists, and physiologists who are using or looking to expand their repertoire of Ca²⁺ techniques.

Tumor progression is driven by mutations that confer growth advantages to different subpopulations of cancer cells. As a tumor grows, these subpopulations expand, accumulate new mutations, and are subjected to selective pressures from the environment, including anticancer interventions. This process, termed clonal evolution, can lead to the emergence of therapy-resistant tumors and poses a major challenge for cancer eradication efforts.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines cancer progression as an evolutionary process and explores how this way of looking at cancer may lead to more effective strategies for managing and treating it. The contributors review efforts to characterize the subclonal architecture and dynamics of tumors, understand the roles of chromosomal instability, driver mutations, and mutation order, and determine how cancer cells respond to selective pressures imposed by anticancer agents, immune cells, and other components of the tumor microenvironment. They compare cancer evolution to organismal evolution and describe how ecological theories and mathematical models are being used to understand the complex dynamics between a tumor and its microenvironment during cancer progression.

The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). This volume will therefore serve as a vital reference for all cancer biologists as well as anyone seeking to improve clinical outcomes for patients with cancer.

Cancer cells often display metabolic changes that distinguish them from normal cells in the body. Their preference for glycolysis over aerobic respiration even in the presence of oxygen was first observed over a century ago; however, it is only over the past two decades that researchers have begun to characterize all the pathways involved and investigate the therapeutic possibilities.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine reviews our understanding of the diversity of metabolic changes seen in cancer cells and their roles in sustaining tumor survival and proliferation. The contributors cover the new technologies being used to monitor metabolism in cells, the Warburg effect and the importance of mitochondria, metabolic signaling, and the importance of redox reactions and antioxidants. Other chapters examine the role of the tumor microenvironment, metal ions, and the immune system.

The book also discusses the role of diet and how studies of patients are revealing how metabolic reprogramming occurs. It will thus be of interest not only to biochemists and oncologists but to all biologists interested in how the behavior of cells is regulated and coordinated.

As the world of biotechnology has grown in leaps and bounds, so too have the career opportunities. But the choices can be daunting. What types of jobs are available? How do you get your foot in the door? What will your job entail if you become a “Preclinical Project Manager” or a “Process Scientist”? What's the difference between biotech and pharma?

Career Opportunities in Biotechnology and Drug Development provides a comprehensive and systematic overview of careers in the life science industry, with all their ups and downs. The author, Toby Freedman, Ph.D., has conducted interviews with hundreds of key players in the industry, who provide first–hand explanations of their day–to–day roles and responsibilities, and offer key insights into how they landed those jobs in the first place. Careers in everything from discovery research to venture capital are covered in detail.

Each chapter includes valuable sections on preparing yourself for a prospective career: educational requirements and personality characteristics needed; recommendations of books, magazines, and Web site resources; and issues to consider regarding salary and compensation. The book also includes interviewing and job searching tips, as well as suggestions on writing a resume specifically for industry.

As the world of biotechnology has grown in leaps and bounds, so too have the career opportunities. But the choices can be daunting. What types of jobs are available? How do you get your foot in the door? What will your job entail if you become a “Preclinical Project Manager” or a “Process Scientist”? What's the difference between biotech and pharma?

Career Opportunities in Biotechnology and Drug Development provides a comprehensive and systematic overview of careers in the life science industry, with all their ups and downs. The author, Toby Freedman, Ph.D., has conducted interviews with hundreds of key players in the industry, who provide first–hand explanations of their day–to–day roles and responsibilities, and offer key insights into how they landed those jobs in the first place. Careers in everything from discovery research to venture capital are covered in detail.

Each chapter includes valuable sections on preparing yourself for a prospective career: educational requirements and personality characteristics needed; recommendations of books, magazines, and Web site resources; and issues to consider regarding salary and compensation. The book also includes interviewing and job searching tips, as well as suggestions on writing a resume specifically for industry.

Most people who do a PhD and postdoctoral work in the biomedical sciences do not end up as principal investigators in a research lab. Despite this, graduate courses and postdoctoral fellowships tend to focus almost exclusively on training for bench science rather than other career paths. This book plugs the gap by providing information about a wide variety of different careers that individuals with a PhD in the life sciences can pursue.

Covering everything from science writing and grant administration to patent law and management consultancy, the book includes firsthand accounts of what the jobs are like, the skills required, and advice on how to get a foot in the door. It will be a valuable resource for all life scientists considering their career options and laboratory heads who want to give career advice to their students and postdocs.

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Regulated cell death, which is involved in nearly every aspect of animal development and physiology, can be challenging to study in the laboratory. There are multiple types of cell death, several interconnected signaling pathways can be activated, and the postmortem consequences may vary. Therefore, a combination of specialized techniques is often required to characterize and confirm cell death in the system of interest.

This laboratory manual provides a comprehensive suite of step-by-step protocols for inducing, detecting, visualizing, characterizing, and quantifying cell death in a variety of systems. The contributors describe strategies for identifying and evaluating the biochemical and morphological changes that occur during apoptosis, autophagy, necrosis, and other forms of cell death, as well as for pinpointing the genes and proteins that may be involved. The protocols employ flow cytometry, imaging and microscopy, RNAi, western blotting, enzymatic activity measurements, and other tools to assess phenomena such as DNA fragmentation, lysosomal membrane permeabilization, autophagic flux, apoptosome or ripoptosome formation, caspase activation, and cytochrome c release. Techniques are described for both in vitro systems and in vivo models, including mice, C. elegans, and Drosophila.

The authors also provide guidance on interpreting and presenting the results of cell death experiments, as well as advice on complementary procedures that may be required to confirm the results of a given experiment. This indispensable laboratory resource will enable all cell and developmental biologists, from the graduate level upward, to confidently carry out and comprehend a wide array of cell viability assays.

Regulated cell death, which is involved in nearly every aspect of animal development and physiology, can be challenging to study in the laboratory. There are multiple types of cell death, several interconnected signaling pathways can be activated, and the postmortem consequences may vary. Therefore, a combination of specialized techniques is often required to characterize and confirm cell death in the system of interest.

This laboratory manual provides a comprehensive suite of step-by-step protocols for inducing, detecting, visualizing, characterizing, and quantifying cell death in a variety of systems. The contributors describe strategies for identifying and evaluating the biochemical and morphological changes that occur during apoptosis, autophagy, necrosis, and other forms of cell death, as well as for pinpointing the genes and proteins that may be involved. The protocols employ flow cytometry, imaging and microscopy, RNAi, western blotting, enzymatic activity measurements, and other tools to assess phenomena such as DNA fragmentation, lysosomal membrane permeabilization, autophagic flux, apoptosome or ripoptosome formation, caspase activation, and cytochrome c release. Techniques are described for both in vitro systems and in vivo models, including mice, C. elegans, and Drosophila.

The authors also provide guidance on interpreting and presenting the results of cell death experiments, as well as advice on complementary procedures that may be required to confirm the results of a given experiment. This indispensable laboratory resource will enable all cell and developmental biologists, from the graduate level upward, to confidently carry out and comprehend a wide array of cell viability assays.

A million cells in our bodies die every second—they commit suicide by activating a process called apoptosis or other forms of programmed cell death. These mechanisms are essential for survival of the body as a whole and play critical roles in various developmental processes, the immune system, and cancer.

In this second edition of Douglas Green’s essential book on cell death, Green retains the bottom-up approach of the first edition, starting with the enzymes that carry out the execution (caspases) and their cellular targets before examining the machinery that connects them to signals that cause cell death. He also describes the roles of cell death in development, neuronal selection, and the development of self-tolerance in the immune system, as well as how the body uses cell death to defend against cancer.

The new edition is fully updated to cover the many recent advances in our understanding of the death machinery and signals that control cell death. These include the mechanisms regulating necroptosis, mitophagy, and newly identified processes, such as ferroptosis. The book will thus be of great interest to researchers actively working in the field, as well as biologists and undergraduates encountering the topic for the first time.

Most animal cells are polarized, with structurally and functionally distinct regions. This polarization facilitates processes such as differentiation and morphogenesis, directional cell migration, nerve impulse transmission, and transport of molecules across tissues. The dysregulation of these processes can lead to developmental disorders and is a feature of many cancers.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology reviews our understanding of the molecular mechanisms involved in establishing and maintaining cell polarity, as well as their relevance for human disorders. Contributors discuss how cells coordinate signaling pathways, membrane trafficking, and cytoskeletal remodeling to ensure proper spatial arrangement of cellular components. Processes such as transcytosis, exocyst-mediated vesicle trafficking, and endosomal sorting are covered in detail. Throughout, the focus is on epithelial cells and how polarity mechanisms facilitate the development of their apical and basolateral surfaces, tube formation (e.g., in blood vessel development), exchange of waste and nutrients, and the generation and maintenance of specialized structures at the cell surface (e.g., cilia).

The authors also describe the polarity mechanisms involved in collective cell migration, a phenomenon seen during morphogenesis and cancer metastasis. This volume will thus be essential reading for all cell and developmental biologists, as well as those interested in how cell polarity processes impact human health and disease.

In multicellular organisms, cell death is required for normal development, homeostasis, and the elimination of infected or injured cells. The mechanisms by which cell death occurs are genetically encoded and carefully controlled. Perturbations that enhance or suppress cell death may lead to cancer, neurodegeneration, and inflammatory diseases.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive update on the cell signaling that underlies the main cell death programs (apoptosis, pyroptosis, and necroptosis) and how this knowledge is driving the development of therapeutic drugs to treat some human diseases. Contributors describe in detail the molecular mechanisms of cell death signaling and the myriad players involved, including death receptor–ligand systems, BCL-2 family proteins, caspases, inflammasomes, gasdermin, MLKL, RIPK1, A20, and XIAP. They also examine the involvement of cell death programs in various pathologies and the therapeutic potential of inhibiting key pathway components.

Chapters are additionally devoted to cell death signaling mechanisms in plants and lower organisms, as well as the evolution of those mechanisms and the influence of pathogens that seek to evade them. This volume is therefore an essential reference for cell and developmental biologists, cancer biologists, and all who wish to explore recent progress in our understanding of cell death programs.

Neighboring cells are linked to each other by multimolecular complexes such as adherens junctions, desmosomes, and gap junctions. These complexes help maintain tissue integrity, act as barriers to permeability, reinforce cell polarity, and allow cells to communicate with each other.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology reviews our understanding of the organization, regulation, and dynamics of cell–cell junctions and the roles they play in morphogenesis, tissue homeostasis, and disease. The contributors examine the assembly and structure of different cell–cell adhesion systems, the plasticity of cell–cell junctions (e.g., during cell migration), and how the junctions act as hubs to sense and transduce various mechanical and chemical signals.

The authors also discuss the roles of cell–cell junctions in specific developmental and physiological processes, such as hearing, skeletal myogenesis, and neural circuit assembly, as well as in diseases such as cancer. This volume is therefore an indispensable reference for cell and developmental biologists, as well as anyone interested in understanding the roles of these complexes in human health and disease.

The human genome is packaged into chromatin, which is composed of numerous proteins that help control gene expression, DNA replication and repair, and genome stability. In recent years, it has become clear that the deregulation of chromatin structure plays an important role in numerous cancers.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the chromatin components that are commonly mutated, what is understood about the mechanisms that lead to hematological malignancies and solid tumors, and prospects for the therapeutic modulation of chromatin. The contributors describe how histone proteins, histone-modifying enzymes, chromatin remodelers, transcriptional regulatory complexes, enhancer-associated factors, and signaling proteins are dysregulated in cancer pathogenesis. In addition, the roles of DNA methylation and noncoding RNAs are covered.

The authors also discuss small molecules and other drugs that are currently under development or already used to treat cancer (e.g., HDAC inhibitors and DNA hypomethylating agents). This book is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists interested in understanding cancer therapies.

The 82nd Cold Spring Harbor Symposium focused on Chromosome Segregation & Structure and addressed the enormous progress in our understanding of the nature and behavior of chromosomes during the life cycle of the cell. It is rare to find such a wide-ranging perspective on this topic in one volume and this collection of papers will be valuable to investigators interested in many aspects of cell biology, genetics, and cancer. The topics covered at the meeting included Meiosis; Mitosis; Chromosome Segregation; Centrosomes and Centrioles; Ploidy, Chromosome Segregation Errors, and Disease; Asymmetric Cell Division; Nuclear Architecture; Chromosome Structure and Condensation; Sister Chromatid Cohesion; Genome Stability; and Germ Cells. Numerous speakers participated in interviews during the course of the Symposium week and transcripts of those discussions and the Dorcas Cummings lecture by David Page are included.

The 82nd Cold Spring Harbor Symposium focused on Chromosome Segregation & Structure and addressed the enormous progress in our understanding of the nature and behavior of chromosomes during the life cycle of the cell. It is rare to find such a wide-ranging perspective on this topic in one volume and this collection of papers will be valuable to investigators interested in many aspects of cell biology, genetics, and cancer. The topics covered at the meeting included Meiosis; Mitosis; Chromosome Segregation; Centrosomes and Centrioles; Ploidy, Chromosome Segregation Errors, and Disease; Asymmetric Cell Division; Nuclear Architecture; Chromosome Structure and Condensation; Sister Chromatid Cohesion; Genome Stability; and Germ Cells. Numerous speakers participated in interviews during the course of the Symposium week and transcripts of those discussions and the Dorcas Cummings lecture by David Page are included.

Nearly every cell in the human body has one or more protrusive structures called cilia or flagella. These power cell movement and fluid flow, sense the extracellular environment, coordinate cell signaling, and establish left-right asymmetry during development. Mutations in genes that encode cilia can lead to disorders known as ciliopathies.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology examines key aspects of ciliary biology—from the molecular to the organismal level—in normal physiology and disease. The contributors dissect the complex structures of motile and nonmotile (primary) cilia, discuss how the intraflagellar transport machinery moves cargo across the central axoneme, and review how the ciliary gate controls the composition of cilia and flagella. The roles of cilia in coordinating cellular responses to environmental stimuli via cell signaling pathways (e.g., Hedgehog) are also covered, as are physiological functions in processes such as fertilization, mucociliary clearance, and vision.

The authors also survey the wide spectrum of ciliopathies, describing their genetic bases, pathogenic mechanisms, and clinical manifestations. This volume is therefore an indispensable reference for all cell and developmental biologists, as well as medical geneticists and clinical scientists wishing to understand and treat disorders involving ciliary dysfunction.

Our daily routines and physiological functions&#151and those of virtually all living organisms&#151are synchronized with the Earth's rotation about its axis. These include sleep patterns, hormone secretion, blood pressure, body temperature, and feeding behavior. Oscillations in these processes, or circadian rhythms, are controlled by molecular feedback loops that integrate with environmental and metabolic stimuli.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology examines the molecular and cellular details of the oscillatory machinery and how they control aspects of our physiology. Contributors discuss the cell-autonomous generation of circadian time and how those mechanisms interact with circuit-level mechanisms in the suprachiasmatic nucleus. Links between circadian and redox systems, as well as the relationship between circadian oscillations and pathogenic infections, are also covered.

In addition, the authors examine circadian rhythms in other species (e.g., plants and Drosophila) and how they enable the organisms to adapt to their environments. This volume will therefore serve as a valuable reference for not only neurobiologists and cell and molecular biologists, but all who wish to understand the clocks and rhythms of life.

The Proceedings of the 79th Symposium capture many of the tremendous discoveries currently being made by neuroscientists and psychologists working on cognitive processes at scales varying from the molecular to circuit to whole-brain and theoretical studies. Major advances in understanding cognitive function, including learning, memory, language, and decision-making, are being made through the application of powerful new techniques and approaches. The scientific results discussed in this volume shed light on many areas of normal brain function but also offer novel insights into the treatment of psychiatric, neurological, and neurodegenerative diseases. This volume includes state-of-the-art neurobiological research at genetic, molecular, cellular, circuit, and whole brain resolution. Additional chapters address computational neuroscience, behavioral and psychophysical studies, and evolutionary/comparative neuroscience. The Conversations included in this volume are based on interviews conducted during the Symposium and offer a broader anecdotal perspective on this fascinating subject by many of the world's leading cognitive neuroscientists. The Symposium Proceedings provides an integrative overview of the current state of the field as well as a glimpse into the emerging connections between molecular/cellular/circuit mechanisms and higher brain function by leading authorities in the field.

The Proceedings of the 79th Symposium capture many of the tremendous discoveries currently being made by neuroscientists and psychologists working on cognitive processes at scales varying from the molecular to circuit to whole-brain and theoretical studies. Major advances in understanding cognitive function, including learning, memory, language, and decision-making, are being made through the application of powerful new techniques and approaches. The scientific results discussed in this volume shed light on many areas of normal brain function but also offer novel insights into the treatment of psychiatric, neurological, and neurodegenerative diseases. This volume includes state-of-the-art neurobiological research at genetic, molecular, cellular, circuit, and whole brain resolution. Additional chapters address computational neuroscience, behavioral and psychophysical studies, and evolutionary/comparative neuroscience. The Conversations included in this volume are based on interviews conducted during the Symposium and offer a broader anecdotal perspective on this fascinating subject by many of the world's leading cognitive neuroscientists. The Symposium Proceedings provides an integrative overview of the current state of the field as well as a glimpse into the emerging connections between molecular/cellular/circuit mechanisms and higher brain function by leading authorities in the field.

In human genetics, causal inference methods leverage large omics data sets and phenotypic information to decipher various cause-and-effect relationships in human health and disease (e.g., alcohol intake and hyptertension). The focus of such work is typically on modifiable variables (e.g., behavior or environmental exposure) that impact disease onset, progression, and outcome. A better understanding of these variables can lead to interventions and therapeutics that have a desirable impact on public health.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines advances in causal inference approaches in human genetics and how they are being used to enhance our understanding of human development and disease. The contributors discuss family-based study designs for causal inference, including twin designs, adoption designs, and in vitro fertilization designs, that separate inherited factors from perinatal environmental exposures. They also review various forms of Mendelian randomization—a population-based approach that is growing in utility and popularity—as well as their integration with family-based designs.

The use of these approaches to investigate causal mechanisms in specific scenarios (e.g., maternal smoking during pregnancy and ADHD in offspring) is also covered. This volume is therefore an essential read for geneticists, epidemiologists, and all biomedical scientists and public health professionals dedicated to using genetic information to improve human health.

An English translation of Boveri's famous monograph which was first
published in Germany in 1914.

Written almost a hundred years ago,
Theodor Boveri's Zur Frage der Entstehung maligner Tumoren has had a
momentous impact on cancer research. In it he argues that malignancy
arises as a consequence of chromosomal abnormalities and that
multiplication is an inherent property of cells. With astonishing
prescience, Boveri predicts in this monograph the existence of tumor
suppressor mechanisms and is perhaps the first to suggest that
hereditary factors (genes) are linearly arranged along chromosomes. This
new translation by Sir Henry Harris, Regius Professor of Medicine
Emeritus at Oxford University and former Editor-in-Chief of Journal of
Cell Science, includes extensive annotations in which he discusses the
relevance of Boveri's views today. It is essential reading for all
cancer researchers, as well as those interested in the history of
cytogenetics and cell biology.

An essential guide for academic scientists and physicians who are considering consulting work in biomedicine

Before signing a consulting agreement, this must-have reference will help you understand the key issues to consider—from intellectual property, confidentiality, and compensation, to often overlooked issues such as indemnity, different classes of stock, and the relevance of insider trading and securities laws. 

Read Connecting with Companies and you will:

• Gain invaluable, first-hand advice from the authors: a leading attorney and a Nobel Laureate in Physiology or Medicine, both with extensive experience reviewing and negotiating consulting agreements


• Receive guidance for academics, lawyers, accountants, auditors, venture capitalists, and technology transfer departments of universities, hospitals, and research organizations


• Understand crucial start-up issues such as 83b tax election and participating preferred stock





For more information visit Bioagreements.org




Connecting with Companies is an invaluable resource for students, staff, and faculty. To assist you with ordering multiple copies for your institution, we’ve set up the following discount options:

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Henri Termeer was one of the first of a pioneering group of business executives who built a disparate group of fledgling companies into a biotech industry that has driven decades of therapeutic innovation. During a 28-year career at Genzyme, including 26 years as CEO, he created a process of drug development that for the first time was patient-centered. He also helped forge biotech's public policy agenda and inspired a generation of entrepreneurs to take on large and important challenges. An extraordinary number of today's biotech leaders were directly mentored by Termeer. His own leadership was iconoclastic: He broke rules and took risks, setting ambitious goals and finding novel ways to reach them. In doing so he transformed an industry and brought hope to patients with a range of diseases previously deemed too rare to justify the investment needed to support the development of specific therapies.
In Conscience and Courage, John Hawkins, an insightful analyst of healthcare leaders, reveals the philosophy, principles, methods, and habits of a prominent and successful CEO who defied convention to create an investor-owned global enterprise that put people before profits and improved the lives of thousands of forgotten patients.

Advanced praise:

“Without Henri Termeer, patients with rare diseases would have no hope for new medicines. This authoritative book brings home the highs and the lows
of Henri's crusade for rare disease patients and families everywhere. For anyone who really wants to know what ‘patient-centric' means, this one's a must-read.”

—John Maraganore, CEO, Alnylam Pharmaceuticals

“Henri Termeer, through his relentless commitment to patients, created a winning global company and unleashed the era of transformative medicines for rare disease. His astonishing business acumen is only surpassed by his humanity-care for individual patients, his colleagues, his family, and his friends. John Hawkins masterfully captures the incredible business story as well as the amazing essence of the man.”

—Deborah Dunsire, MD, President & CEO, H. Lundbeck A/S

“Henri Termeer led a remarkable life. By pioneering the treatment of rare diseases, he transformed the lives of many forgotten patients and families. John Hawkins' account captures this passion and purpose beautifully.”

—Robbie Huffines, Global Chairman, Investment Banking, JP Morgan & Co.

“Henri Termeer was a pioneer of the biotechnology industry, combining an astute business mind with a deep passion and empathy for patients and their families. He shaped, almost out of whole cloth, a company that would shine a light on the path to better medicines to an historically underrepresented group of patients and, in so doing, built Genzyme into a formidable enterprise. John Hawkins tells this story with insight, wit, and warmth, painting an indelible portrait of a remarkable man.”

—Vicki L. Sato, PhD, Chairman, Denali Therapeutics

“Henri Termeer was among the most talented entrepreneurs I have encountered in my career. His drive, determination, and especially his strategic vision profoundly impacted not only Genzyme, but also the evolution of the biotechnology industry and the development of innovative, new drugs for rare disease patients worldwide. Henri was also a true business statesman in both Boston and the Region who contributed to the prosperity Massachusetts has achieved. John Hawkins’ book captures the richness, depth and complexity of Henri’s life story and his many contributions. His deep research and colorful writing make this a great read.”

—Professor Michael Porter, University Professor, Harvard Business School

“If any leader ever took risks and founded a humanitarian movement, it was Henri Termeer. A thoughtful man driven by what many viewed as an impossible-to-achieve vision, he recruited and encouraged other leaders, many of whom formed new companies, to push on a frontier that he knew was much bigger than he alone could conquer. This is a wonderful, inspirational book which brilliantly describes the high character of an underappreciated, modern-day hero, a man who has improved, and in some cases saved, the lives of millions who will never know his name.”

—Professor Carl J. Schramm, Former President of The Ewing Marion Kauffman Foundation and Seven-times Author, including Burn the Business Plan

“The prospects for children born with genetic diseases today are vastly different than they were before Henri Termeer defied convention to build Genzyme. John Hawkins has brought Henri vividly to life on the pages of this book. This is sure to be an inspirational read for anyone interested in understanding how Termeer took such a courageous path to transform the outlook for rare disease patients, giving hope to millions.”

—James Geraghty, Former Genzyme Executive and Chairman, Orchard Therapeutics

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In this brief, readable, and revealing book, one of the pioneers
of the now rapidly evolving field of DNA repair traces the history of
the discovery of the more important mechanisms by which cells respond
to DNA damage. Errol Friedberg has written an enjoyable and informative
introduction to the study of DNA mutagenesis and re-pair that will
interest students at an advanced undergraduate or graduate student
level as well as investigators in fields as diverse as oncogenesis,
cell cycle regulation, transcription and DNA replication.

The development of CRISPR-Cas technology is revolutionizing biology. Based on machinery bacteria use to target foreign nucleic acids, these powerful techniques allow investigators to edit nucleic acids and modulate gene expression more rapidly and accurately than ever before.

Featuring contributions from leading figures in the CRISPR-Cas field, this laboratory manual presents a state-of-the-art guide to the technology. It includes step-by-step protocols for applying CRISPR-Cas-based techniques in various systems, including yeast, zebrafish, Drosophila, mice, and cultured cells (e.g., human pluripotent stem cells). The contributors cover web-based tools and approaches for designing guide RNAs that precisely target genes of interest, methods for preparing and delivering CRISPR-Cas reagents into cells, and ways to screen for cells that harbor the desired genetic changes. Strategies for optimizing CRISPR-Cas in each system—especially for minimizing off-target effects—are also provided.

Authors also describe other applications of the CRISPR-Cas system, including its use for regulating genome activation and repression, and discuss the development of next-generation CRISPR-Cas tools. The book is thus an essential laboratory resource for all cell, molecular, and developmental biologists, as well as biochemists, geneticists, and all who seek to expand their biotechnology toolkits.

The double helix, the genetic code, jumping genes, the PCR technique, the human genome project, RNA interference ...
These and hundreds of other important advances in biology were announced, debated, and distilled at the Cold Spring Harbor
Symposia. These meetings, held each year on tranquil grounds of one of the world's leading research institutes,
have been notable events in biomedical research since 1933.

Now this essential archive, dating from 1933 to 2003, is going online. Learn more about the CSH Symposia Online Archive by visiting the Symposia website.

Cystic fibrosis is caused by mutations in the CFTR gene, which encodes an ion channel protein that regulates anion movement across the epithelial membranes of the lungs, pancreas, and other organs. In cystic fibrosis patients, anion transport is impeded, causing sticky, viscous mucus to build up and clog these vital organs.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine provides an in-depth examination of cystic fibrosis biology and treatment strategies. Contributors examine the structure and dynamics of CFTR, its normal physiological roles in the airway and digestive epithelia, and how those operations are impaired in patients with cystic fibrosis. The numerous CFTR mutations and how they alter the expression, synthesis, processing, and function of CFTR in cystic fibrosis and other CFTR-related disorders are considered, as are disease-modifying genes that influence disease severity.

This volume includes discussions of therapy and treatment strategies for cystic fibrosis, ranging from airway clearance techniques and pancreatic enzyme replacements to the modulation of CFTR and related ion transport pathways. It will be an essential reference for molecular and cellular biologists, physiologists, and clinicians interested in understanding the biological basis of the disease and the search for effective therapies.

Cytokines (e.g., interleukins and interferons) are small signaling proteins that are essential for communication between cells. They are important regulators of the immune system, helping to control lymphocyte development and function, orchestrate inflammation, and defeat microbial and viral invaders. But they also play important roles in the nervous system, embryonic development, and diseases such as cancer.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers the spectrum of cytokines that are produced and their roles in normal physiology and disease. The contributors examine the numerous cytokines and their cognate receptors, the downstream signaling mechanisms (e.g., JAK-STAT pathways) that mediate the effects of cytokines on cells, and the regulators that keep them in check (e.g., long noncoding RNAs and the SOCS and IRF protein families). These molecular interactions are discussed in the context of their physiological effects; the roles of cytokines in the development and activities of the immune system are emphasized.

The authors also explore how the actions of cytokines may be modulated for treating patients with autoimmune disorders, immunodeficiency, infections, allergies, and cancer. Thus, this volume is an indispensable reference not only for cell biologists and immunologists but for all who are interested in targeting cytokine signaling for therapeutic purposes.

The cytoskeleton is the intracellular filament system that controls the morphology of a cell, allows it to move, and provides trafficking routes for intracellular transport. It comprises three major filament systems-actin, microtubules, and intermediate filaments-along with a host of adaptors, regulators, molecular motors, and additional structural proteins.

This textbook presents a comprehensive and up-to-date view of the cytoskeleton, cataloguing its many different components and explaining how they are functionally integrated in different cellular processes. It starts by laying out the basic molecular hardware, before describing in detail how these components are assembled in cells and linked to neighboring cells and the extracellular matrix to maintain tissue architecture. It then surveys the roles of the cytoskeleton in processes such as intracellular transport, cell motility, signal transduction, and cell division. The book is thus essential reading for students learning about intracellular structure. It also represents a vital reference for all cell and developmental biologists working in this field.

In this book, the distinguished geneticist David Botstein offers help and advice to scientists and physicians daunted by the arcane technical terms that flourish in his discipline. The science of gene function has a vocabulary of specialized, sometimes confusing terms to explain how traits and diseases are inherited, how genes are organized and regulated in the genome, and how the genetic code is read and translated by cells. These terms are often a barrier to full understanding of the underlying concepts. Yet, as more and more individuals learn about their genomes, the information these sequences contain cannot be understood or explained without reference to the basic ideas of genetics. Botstein draws on his long experience as a teacher and pioneering scientist to explain and illuminate what many genetic terms mean and how they entered common usage.

Cell and molecular biology are becoming increasingly data driven. Technological advances and increased computing power mean that researchers now increasingly quantify experimental results, rather than simply report qualitative, representative observations. The Digital Cell provides a comprehensive guide for scientists seeking to make this transition. It describes how data should be generated and processed, discussing research workflows, pipelines, and storage solutions. A key focus of the book is imaging—image types and formats are explained, as is software for image processing and analysis, along with techniques such as segmentation analysis and automated particle tracking.

The book examines the wide variety of statistical approaches that can be used for data analysis, emphasizing concepts such as significance and reproducibility. It also includes an introduction to coding, including examples of how to write and use R scripts to analyze results. In addition, there is useful advice on how to plot and present data to convey results most effectively. The Digital Cell is thus an essential resource for all cell and molecular biologists—from students embarking on research for the first time to experienced scientists who need to acquire, process, and present their data accurately and efficiently.

The structure of DNA proposed by James Watson and Francis Crick in 1953 was one of the most important scientific discoveries of the twentieth century, transforming biology, giving medicine new impetus, and providing a foundation for the new industry of biotechnology. Jim Watson's best-selling memoir of the events leading to this discovery, The Double Helix, has enthralled millions of readers since its publication in 1968. In this videotaped lecture, recorded live at Cold Spring Harbor Laboratory in November 1999, Dr. Watson retraces those events in a very personal reminiscence of the period and the people involved. This is an account of one of the great dramas of science, told from the intimate perspective of a participant who, aged 25 at the time of the discovery, has become one of the intellectual leaders of our time.

James D. Watson was Director of Cold Spring Harbor Laboratory, New York, from 1968 to 1993 and is now its President. He was the first Director of the National Center for Human Genome Research of the National Institutes of Health from 1989 to 1992.

Dr. Watson is a member of the National Academy of Sciences and Royal Society and has received many awards and honors, including the Presidential Medal of Freedom and the National Medal of Science. In addition to The Double Helix, his books include Molecular Biology of the Gene, Molecular Biology of the Cell, Recombinant DNA, and A Passion for DNA.

“DNA has come a long way.” James D. Watson, Nobel Laureate

DNA Interactive (DNAi) is a multimedia resource for high school and introductory college biology that shows how we came to understand the language of DNA, how we bend it to our own service, and what it can tell us about who we are. The DNAi products—an award winning website (http://www.dnai.org) and the DVD—are the result of a two–year collaboration between scientists, educators, and film–makers on three continents. It includes more than 200 video clips and animations; video interviews with 11 Nobel Laureates and more than 50 other scientists, clinicians, and patients; and spectacular 3–D animations that illustrate intracellular processes and explore aspects of DNA science.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Homologous recombination involves the precise exchange of similar or identical nucleic acid sequences between two DNA molecules. This process directs the repair of many DNA lesions in somatic cells and generates genetic variation in sperm and egg cells during meiosis. It is a nearly universal biological process that is conserved from phage to humans.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of recombinational DNA repair, meiotic recombination, and the regulation of these processes. The contributors examine the dozens of proteins that are involved in recombinational repair and the various pathways in which they are employed (e.g., gene conversion or break-induced replication). They also discuss how these proteins and pathways are strictly regulated to avoid genomic instability, which can lead to diseases such as cancer, and how they are coordinated with other nuclear processes (e.g., transcription and DNA replication).

Meiotic recombination, the characteristics that distinguish it from recombinational repair, and effects of its dysregulation (e.g., aneuploidy) are also covered in depth. This volume is an indispensable reference for biochemists, molecular biologists, and cell biologists who want to understand how DNA recombination maintains genomic integrity in individual organisms and across generations.

DNA replication is essential for the propagation of life on Earth. Cells in living organisms must be able to synthesize a complete copy of their DNA with extraordinary precision, so that they can pass this genetic material on to their descendants. DNA replication involves the coordinated interplay and regulation of many complex protein assemblies during the various stages of cell division. When these processes go awry, cancer and other diseases can ensue.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of DNA replication and its control across all domains of life. The contributors examine the molecular machinery involved in the assembly of replication origin complexes, the establishment of replication forks, unzipping of the double helix, priming of DNA synthesis, and elongation of daughter strands. Chromatin organization and dynamics, lagging-strand maturation, telomere replication, and mechanisms to handle errors and damage in DNA are also discussed.

Including examination of the complex interactions between the core replication machinery and the regulatory circuits that drive cell cycle progression, this volume is an indispensable reference for not only biochemists and molecular biologists, but also cell biologists and all who want to understand this fundamental process of life.

This is the second edition of a highly successful textbook (over 50,000 copies sold) in which a highly illustrated, narrative text is combined with easy–to–use thoroughly reliable laboratory protocols. It contains a fully up–to–date collection of 12 rigorously tested and reliable lab experiments in molecular biology, developed at the internationally renowned Dolan DNA Learning Center of Cold Spring Harbor Laboratory, which culminate in the construction and cloning of a recombinant DNA molecule.

Proven through more than 10 years of teaching at research and nonresearch colleges and universities, junior colleges, community colleges, and advanced biology programs in high school, this book has been successfully integrated into introductory biology, general biology, genetics, microbiology, cell biology, molecular genetics, and molecular biology courses.

The first eight chapters have been completely revised, extensively rewritten, and updated. The new coverage extends to the completion of the draft sequence of the human genome and the enormous impact these and other sequence data are having on medicine, research, and our view of human evolution. All sections on the concepts and techniques of molecular biology have been updated to reflect the current state of laboratory research.

The laboratory experiments cover basic techniques of gene isolation and analysis, honed by over 10 years of classroom use to be thoroughly reliable, even in the hands of teachers and students with no prior experience. Extensive prelab notes at the beginning of each experiment explain how to schedule and prepare, while flow charts and icons make the protocols easy to follow.

As in the first edition of this book, the laboratory course is completely supported by quality–assured products from the Carolina Biological Supply Company, from bulk reagents, to useable reagent systems, to single–use kits, thus satisfying a broad range of teaching applications.

"...the point of this story, I'll tell you right now.

Did you ever sit down and think about how

It is that each time a baby's born

It's a baby -- not a rabbit or an ear of corn?"

The answer is in DNA -- the stuff that genes are made of. Twin brothers
Joel and Ira Herskowitz, physician and scientist, respectively, have
come up with a new way to explain to children (ages 8+) how it is that
when a person's genetic message is "copied," the result is another
human being -- not a rabbit or an ear of corn.

Based on a song written by Joel Herskowitz while he was in medical
school, the "Double Talking Helix Blues" is a book and audio presentation on the structure and function of DNA. The book includes
the text for Joel's song, which is illustrated with spectacular
paintings by Judy Cuddihy to provide an important visual component to
the overall "lesson" on DNA.

This is followed by a guide written by Ira Herskowitz to explain the
scientific terms and concepts in the song; this section describes in
clear terms what, for example, a chromosome, nucleus, and molecule
are. Accompanying the book is an audio performances
of the song by Joel and Ira. Click here to listen, or right-click to download the MP3 file now!

All in all, the "Double Talking Helix Blues" provides young readers
with a wonderful introduction to concepts of cells and molecules,
reproduction at the molecular level, and DNA and its structure.
The target age group for this presentation is ages 8 and up, as well
as teachers, scientists, and all those interested in molecular
biology at its most basic level.

This exceptional laboratory manual describes thirty-seven procedures
most likely to be used in the next decade for molecular, biochemical,
and cellular studies on Drosophila. They were selected after
extensive consultation with the research community and rigorously
edited for clarity, uniformity, and conciseness.

The outstanding features of this protocol collection are:

• Scope: The methods included permit investigation
  of chromosomes, cell biology, molecular biology, genomes,
  biochemistry, and development.


• Depth: Each protocol includes the basic
  information needed by novices, with sufficient detail to be valuable
  to experienced investigators.


• Format: Each method is carefully introduced and
  illustrated with figures, tables, illustrations, and examples of the
  data obtainable.


• Added value: The book's appendices include key
  aspects of Drosophila biology, essential solutions, buffers, and
  recipes.

An evolution of Michael Ashburner's 1989 classic Drosophila:
A Laboratory Manual, this book is an essential addition to the
personal library of Drosophila investigators and an incomparable
resource for other research groups with goals likely to require
fly-based technical approaches.

Barbara McClintock was born in 1902, within a few years of the
rediscovery of Mendel's laws. Her life, discoveries, and insights
span the history of genetics in this century.

In the 1920s, she became a dominant figure in the group that
flourished at Cornell University under R.A. Emerson and made
remarkable technical and conceptual advances in maize cytogenetics.
These studies continued at the California Institute of Technology,
in Freiburg, Germany, and at the University of Missouri. In 1942,
she joined the staff of the Carnegie Institution of Washington at
Cold Spring Harbor, New York, where she became a Distinguished
Service Member.

McClintock's unique ability to discern relationships between the
behavior of chromosomes and the properties of the whole organism
earned her early recognition. She was elected to the National Academy
of Sciences in 1944 and to the presidency of the Genetics Society of
America in 1945. Had she done no more, McClintock would have become
a major figure in the history of genetics.

But at Cold Spring Harbor, she began the studies of the consequence
of dicentric chromosome formation and breakage that led her to the
discovery of genetic elements capable of moving within the genome
and controlling expression of other genes. Although McClintock was
universally respected and admired, the first reaction to these
findings was often uncomprehending or indifferent, even dismissive.
In due course, however, the generality of mobile genetic elements
and the concept of a dynamic genome were understood and widely
accepted, culminating in the award to McClintock of an unshared
Nobel Prize in 1983.

As Barbara's 90th birthday approached, some of her many friends and
colleagues were invited to write essays for the occasion. This book
contains a kaleidoscope of contributions, many by those who discovered
transposition in other organisms. Their essays give a remarkable
account of the scientific legacy of one of the century's greatest
geneticists.

Yeast genetics began with Winge's 1935 studies of S. cerevisiae in Copenhagen, and afterwards was pursued by Lindegren in the U.S. and Ephrussi in France. Genetic studies in S. pombe were pioneered by Leupold in the 1940s in Switzerland. Within four decades, not without controversies, both yeast species were recognized as essential models in eukaryotic molecular cell biology. In this remarkable volume, Hall and Linder have assembled the reminiscences of many early investigators whose pioneering studies in the years before 1975 brought yeast biology to its current maturity. These illustrated essays about the science, the events and the personalities involved capture a fascinating era, in the informal style made famous by Phage and the Origins of Molecular Biology. This is a book that all scientists interested in the development of modern genetics and molecular biology should have on their shelves.

Amphibian embryos are supremely valuable in studies of early vertebrate development because they are large, handle easily, and can be obtained at many interesting stages. And of all the amphibians available for study, the most valuable is Xenopus laevis, which is easy to keep and ovulates at any time of year in response to simple hormone injections.

Xenopus embryos have been studied for years but this is a particularly exciting time for the field. Techniques have become available very recently that permit a previously impossible degree of manipulation of gene expression in intact embryos, as well as the ability to visualize the results of such manipulation. As a result, a sophisticated new understanding of Xenopus development has emerged, which ensures the species’ continued prominent position among the organisms favored for biological investigation.

This manual contains a comprehensive collection of protocols for the study of early development in Xenopus embryos. It is written by several of the field’s most prominent investigators in the light of the experience they gained as instructors in an intensive laboratory course taught at Cold Spring Harbor Laboratory since 1991. As a result it contains pointers, hints, and other technical knowledge not readily available elsewhere.

This volume is essential reading for all investigators interested in the developmental and cell biology of Xenopus and vertebrates generally. Many of the techniques described here are illustrated in an accompanying set of videotapes which are cross-referenced to the appropriate section of the manual.

In this classic book, the distinguished science writer Horace Freeland Judson tells the story of the birth and early development of molecular biology in the US, the UK, and France. The fascinating story of the golden period from the revelation of the double helix of DNA to the cracking of the genetic code and first glimpses of gene regulation is told largely in the words of the main players, all of whom Judson interviewed extensively. The result is a book widely regarded as the best history of recent biological science yet published.

This commemorative edition, honoring the memory of the author who died in 2011, contains essays by his daughter Olivia Judson, Matthew Meselson, and Mark Ptashne and an obituary by Jason Pontin. It contains all the content added to previous editions, including essays on some of the principal historical figures involved, such as Rosalind Franklin, and a sketch of the further development of molecular biology in the era of recombinant DNA.

During endocytosis, extracellular molecules and plasma membrane components are selectively internalized by cells. This fundamental process of “cellular ingestion” is required for diverse activities such as nutrient uptake, cell adhesion and migration, signal transduction, cytokinesis, neurotransmission, and antigen presentation. Pathogens (e.g., HIV) exploit endocytic pathways to gain entry into cells, and defects in the endocytic machinery can lead to diseases such as cancer.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all of the major pathways of endocytosis and postendocytic trafficking and how they regulate cellular and organismal physiology. Contributors describe how cargo enters the cell via clathrin-mediated and clathrin-independent pathways, including caveolar endocytosis, micropinocytosis, cholesterol-sensitive endocytosis, phagocytosis, and the CLIC/GEEC pathway. They review the numerous machineries (e.g., Rab GTPases, tethering factors, and retromer) that transport cargo through endosomes and deliver it to lysosomes or recycle it back to the cell surface, and the signals and mechanisms governing these sorting decisions. Topics such as lysosomal dynamics, the biophysical challenges of bending membranes, and the evolution of endocytic systems are also covered.

This volume also includes substantial discussion of the roles of endocytic trafficking in organismal development, physiology, and disease. It is thus an indispensable reference for cell biologists, but also for neuroscientists, immunologists, developmental biologists, microbiologists, and others concerned with the physiological and therapeutic implications of this key cellular process.

The endoplasmic reticulum (ER) is an extensive network of membranes that folds, modifies, and transports proteins in eukaryotic cells. It also manufactures lipids and interacts extensively with other organelles, playing essential roles in cell growth and homeostasis.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of ER morphology and function, as well as its interactions with the nucleus, Golgi, and mitochondria. Contributors examine how proteins translocate across the ER membrane, the processes that occur inside the ER lumen (e.g., folding, glycosylation, and disulfide bond formation), and how the proteins are packaged into vesicles and transported to the Golgi. They also review quality-control mechanisms that are employed by the ER to detect and eliminate misfolded or unassembled proteins. Lipid synthesis and transport are also discussed.

This volume covers not only the biochemistry and cell biology of the ER, but also ER stress, metabolism, and the role of the ER in viral replication. Thus, it is an essential reference for cell biologists, physiologists, and pathologists interested in understanding the numerous functions of the ER.

The endoplasmic reticulum (ER) is a network of membranes that folds, modifies, and transports proteins in eukaryotic cells. It also manufactures lipids and interacts extensively with other organelles, playing essential roles in cell growth and homeostasis.

Written and edited by experts in the field, this new collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive update on advances in our understanding of the structure and multiple functions of the ER. The contributors examine how proteins enter the ER, the biogenesis of membrane proteins, and the role of the ER in protein sorting and quality control. In addition, they discuss how lipids are synthesized and transported to and from the ER.

The volume reviews the architecture of the ER and the ways in which it interacts with other organelles. The consequences for metabolic health and neurodegeneration are also considered. It is thus an essential reference for cell biologists, as well as physiologists and pathologists interested in understanding the role of the ER in disease.

Agriculture plays a vital role supporting human life on Earth but faces significant challenges to feed the growing population.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology examines the molecular bases of plant traits and addresses how this knowledge can be used to develop crops that are resilient to a changing environment. The contributors review recent advances in our understanding of plant plasticity, circadian rhythms, stomatal development, inflorescence architecture, symbiotic phosphate acquisition, and specialized plant metabolism and discuss how this knowledge might be used to boost yields, improve tolerance to pathogens and environmental stress, and enhance nutritional content. The book also discusses the development and socioeconomic impact of deployment of genetically improved submergence-tolerant rice. The generation of blight-resistant American chestnut trees—the first bioengineered plant developed with the goal of ecological restoration—is also described. This volume is therefore an essential read for all plant biologists, geneticists, and engineers interested in addressing agricultural and environmental challenges.

Beneath your skin there is an amazing hidden world of living cells. Millions and millions
of cells work together, to make everything that is you. But did you know that you started
life as just one tiny cell? And did you know that everything that lives on Planet Earth is
also made of these amazing cells?

Color and learn! Beneath your skin there is an amazing hidden world of living cells. Millions and millions of cells work together, to make everything that is you. But did you know that you started life as just one tiny cell? And did you know that everything that lives on Planet Earth is also made of these amazing cells?

From the acclaimed creative partnership of scientist/author Fran Balkwill and illustrator Mic Rolph, the Enjoy Your Cells Color and Learn Series is an entertaining, one-of-a-kind learning experience that you help to create. Each coloring book incorporates all of the original text and artwork from the best-selling Enjoy Your Cells series, now in a delightfully enlarged format suitable for coloring book fans of all ages. The pages are brimming with dozens of drawings of cells, proteins, and DNA, accompanied by easy-to-understand but scientifically accurate commentary. Proceeds from the books help to support research and education at the world-renowned Cold Spring Harbor Laboratory.

With exuberant graphics ranging from simple to intricate, these books are sure to bring hours of educational enjoyment to budding and experienced scientists alike!

Color and learn! Enjoy Your Cells is a series of children's books from the acclaimed creative partnership of scientist/author Fran Balkwill and illustrator Mic Rolph. Once again, they use their unique brand of simple but scientifically accurate commentary and exuberant graphics to take young readers on an entertaining exploration of the amazing, hidden world of cells, proteins, and DNA.

This four-volume set includes all of the coloring books in the series, bundled together with a box of premium quality, pre-sharpened colored pencils, and a colorful sheet of water-resistant stickers inspired by the series (pencils and stickers available while supplies last). It's the perfect gift for the scientist of any age!

Discover all the books in the ENJOY YOUR CELLS series, each available in coloring book and full-color formats!
Recommended for ages 7 and up.

Enjoy Your Cells is a new series of children's books from the acclaimed creative partnership of scientist/author Fran Balkwill and illustrator Mic Rolph. Once again, they use their unique brand of simple but scientifically accurate commentary and exuberantly colorful graphics to take young readers on an entertaining exploration of the amazing, hidden world of cells, proteins, and DNA.

It's over ten years since Fran and Mic invented a new way of getting science across to children. Think what extraordinary advances have been made in biology in that time—and how often those discoveries made headlines. Stem cells, cloning, embryo transfer, emerging infections, vaccine development…here in these books are the basic facts behind the public debates. With these books, children will learn to enjoy their cells and current affairs at the same time. And they're getting information that has been written and reviewed by working scientists, so it's completely correct and up-to-date. Readers aged 7 and up will appreciate the stories' lively language and with help, even younger children will enjoy and learn from the jokes and illustrations—no expert required!

This series is a must for all elementary school students and those who care about educating them to be well-informed in a world of increasingly complex health-related and environmental issues.

Fran Balkwill is Professor of Cancer Biology at St. Bartholomew's Hospital and the London Queen Mary School of Medicine. Mic Rolph is a graphic designer with much television and publishing experience. Together, they have created many books for children, and have won several awards, including the prestigious COPUS Junior Science Book Prize.

Volumes:

Enjoy Your Cells

Germ Zappers

Have a Nice DNA!

Gene Machines

Viruses that are transmitted via the fecal–oral route and may cause liver damage are known as enteric hepatitis viruses. These viruses, which include the hepatitis A and E viruses (HAV and HEV, respectively), infect millions of individuals worldwide and pose significant threats to public health.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines recent progress in our understanding of the biology and pathogenic mechanisms of HAV and HEV, as well as prospects for improving their control. Contributors explore the molecular characteristics and life cycles of HAV and HEV, their interactions with the liver and immune system, the clinical manifestations of the infections they cause, and their transmission via contaminated food and water. Additional topics include the geographic distributions of the various HAV and HEV genotypes, factors that influence their changing epidemiology, and the development of effective vaccines and vaccination strategies.

The authors also discuss advances in cell-culture systems and animal models, as well as how studies of HAV and HEV may provide insight into other viruses and infectious diseases of the liver. This volume is therefore an essential reference for all virologists, immunologists, pathologists, clinicians, and public health professionals.

In many biological processes the regulation of gene expression involves epigenetic mechanisms. In this new edition of Epigenetics, 36 chapters written by experts in the field introduce and explain epigenetic effects from many perspectives. These include the varied molecular mechanisms underpinning epigenetic regulation, discussion of cellular processes that rely on this kind of regulation, and surveys of model organisms in which epigenetic effects have been most studied.

The original chapters have all been rewritten and brand new chapters cover topics such as the structure, function, and dynamics of histone-modifying enzymes and histone-interacting proteins. Other chapters address chromatin remodeling, DNA methylation, siRNAs, and gene silencing; X-chromosome inactivation, dosage compensation, and imprinting; and epigenetics in microbes, plants, insects, and mammals.

How epigenetic mechanisms act in cell division and cell type specification, and how errors in these pathways contribute to cancer and other human diseases are also considered, along with the importance of epigenetics for induced pluripotency and reprogramming. In addition, new chapters describe the involvement of epigenetic processes in epigenetic inheritance, neuronal development, metabolism and signaling, responses to the environment, and long-range chromatin interactions. A series of short essays highlight important recent discoveries.

All the chapters provide conceptual illustrations that help readers understand epigenetic control. The book is thus a benchmark text for advanced undergraduate and graduate courses on gene regulation, as well as an essential resource for scientists interested in this rapidly moving field.

Epilepsy is due to abnormal signaling of neurons in the brain that can cause seizures. It is a common condition, affecting at least 3% of individuals at some point during their life. The seizures are difficult to predict and, in a significant fraction of patients, refractory to current medical interventions.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine includes contributions covering all aspects of epilepsy, its causes, pathophysiology, clinical characteristics, comorbidities, and treatment. Contributors discuss the genetic, developmental, and environmental triggers of recurrent seizures; molecular changes (e.g., epigenetic modifications) that are associated with epileptogenesis; and the aberrant ion channels and neuronal networks involved. Clinical aspects of the disease (diagnosis, classification, and treatments) are reviewed, as are common comorbidities (e.g., depression and cognitive disorders). Recent advances in drug development and surgical techniques aimed at reducing the morbidity and mortality of patients with epilepsy are also described.

The authors highlight current challenges in the field of epilepsy, with the goal of assisting others in formulating relevant research questions. This volume is therefore a vital reference not only for scientists and clinicians currently working in the field, but for all neuroscientists seeking to explore new research directions.

Epilepsy is due to abnormal signaling of neurons in the brain that can cause seizures. It is a common condition, affecting at least 3% of individuals at some point during their life. The seizures are difficult to predict and, in a significant fraction of patients, refractory to current medical interventions.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine includes contributions covering all aspects of epilepsy, its causes, pathophysiology, clinical characteristics, comorbidities, and treatment. Contributors discuss the genetic, developmental, and environmental triggers of recurrent seizures; molecular changes (e.g., epigenetic modifications) that are associated with epileptogenesis; and the aberrant ion channels and neuronal networks involved. Clinical aspects of the disease (diagnosis, classification, and treatments) are reviewed, as are common comorbidities (e.g., depression and cognitive disorders). Recent advances in drug development and surgical techniques aimed at reducing the morbidity and mortality of patients with epilepsy are also described.

The authors highlight current challenges in the field of epilepsy, with the goal of assisting others in formulating relevant research questions. This volume is therefore a vital reference not only for scientists and clinicians currently working in the field, but for all neuroscientists seeking to explore new research directions.

Saccharides are widely distributed in all living life-forms, and glycobiology is the study of their structure, biosynthesis, biology, and evolution. It is a rapidly growing field, relevant to many areas of basic research, biomedicine, and biotechnology. The field includes the chemistry of carbohydrates, the enzymology of glycan formation and degradation, the recognition of glycans by specific proteins, the roles of glycans in complex biological systems, and their analysis and manipulation. Essentials of Glycobiology is the field's most authoritative textbook, offering an overview suitable for advanced undergraduates and graduate students in molecular and cellular biology and biomedicine. In an entirely revised and updated fourth edition, the book retains a broad focus and applicability to fields ranging from biology and medicine to chemistry and materials science, with excellent artwork and chapters written by an international selection of leading investigators.