It is the great glory as it is also the great threat of science that everything which is in principle possible can be done if the intention to do it is sufficiently resolute. Peter Medawar, "The Threat and the Glory" An international symposium on "Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease" was held at EI Escorial (Spain) from July 5-9, 1993 as a summer course of the Complutense University in Madrid. The lectures were delivered by renowned scientists from Europe, America, and Asia and attended by a large number of young scientists and graduate students from many countries. During evolution multicellular organisms have developed the most sophisticated and heterogeneous signals to maintain in harmony their multiple functions. The latest and most controversial aspects and developments in signal transduction were the main focus of this course. The communication among participants was extremely fluid, alive, and warm. This allowed the understanding of the key steps in cellular communication, from their original and historical sources to the main present hypothesis in the borderline of the latest scientific discoveries in this field. Without any doubt, the special atmosphere of the place, the monuments and the old granite stones, the "patio" with the fountain and the rose garden were responsible for the cordial meeting. This book comprises the manuscripts of the participants and we hope it will contribute to our knowledge of cellular signal transduction and be of value to a wider scientific community.

The field of DNA repair is vast and advancing rapidly. Recent investigations have begun to focus on the involvement of chromatin in the repair of broken DNA. Although I have no doubt that many breakthroughs in our understanding of chromatin, chromatin regulation, and DNA repair lie in our future, presently this is a new line in inquiry. As such there are many, many unanswered questions. Indeed, most of the correct questions have probably not even been asked yet. Here I have attempted to present a review of some of the current body of knowledge that may prove relevant to understanding the role of chromatin in DNA repair. Because the volume of research, and the relevant findings, come from a staggering array of labs, systems, and ideas I have focused primarily on findings developed from the study of the budding yeast Saccharomyces cerevisiae. Unfortunately, this means that I have left out a great deal of information. It is my hope, however, that the information I do detail, particularly in Chapter 1, will give a flavor for the scope of the problem and perhaps highlight some of the interesting directions this field is taking, or may one day take. I would also point out that the primary research that is presented herein is not in any way meant to represent the comprehensive scope of research being performed. To understand DNA repair will require investigation from innumerable labs, performed by innumerable researchers, moving in unexpected directions.

4 Water Sources ........................................ 149 Criteria ............................................. 149 Major types .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 . . . . . . . . . . . . Summary ............................................ 152 5 Water Treatment ...................................... 155 Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 . . . . . . . . . . . . Materials ............................................ 155 Treatment options . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 . . . . . . . . . . . System design ........................................ 169 System monitoring and control . . . . . . . . . . . . . . . . . . . . . 172 . . . . . . . . Environmental considerations .............................. 174 Summary ............................................ 174 6 Culture Units ......................................... 175 Considerations in choosing culture units ...................... 175 Characteristics of culture units . . . . . . . . . . . . . . . . . . . . . 175 . . . . . . . . Applications of culture units .............................. 191 Hatchery design " . . . . . . . . . . . . . . . . . . . . . . . . . . 208 . . . . . . . . . . . Summary ............................................ 210 7 Obtaining Fish for Stocking . ............................. 211 Stock from the wild .................................... 211 Stock from the hatchery ................................. 211 Spermatogenesis (sperm formation) ....................... 232 Oogenesis (egg formation) ............................. 232 Oocyte maturation ................................... 233 Endocrine control of oocyte maturation and ovulation .......... 237 fuduced ovulation . . . . . . . . . . . . . . . . . . . . . . . . . . 238 . . . . . . . . . . Timing and egg quality . . . . . . . . . . . . . . . . . . . . . . . 257 . . . . . . . . . Artificial fertilization ................................. 265 Care of eggs ....................................... 267 Storage of gametes ................. ' .................. 269 Natural ovulation . . . . . . . . . . . . . . . . . . . . . . . . . . 270 . . . . . . . . . . Care of broodfish . . . . . . . . . . . . . . . . . . . . . . . . . . 289 . . . . . . . . . . Egg collection .. . . . . . . . . . . . . . . . . . . . . . . . . . . 290 . . . . . . . . . . fuduced vs natural ovulation ............................ 290 Broodfish adaptability . . . . . . . . . . . . . . . . . . . . . . . . . 291 . . . . . . . . . . Examples ............................................ 291 Genetic considerations . . . . . . . . . . . . . . . . . . . . . . . . . 295 . . . . . . . . . . Hybridization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 . . . . . . . . . . . . Sex control .......................................... 296 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 . . . . . . . . . . . . . vi 8 Nutrition of Larval Fish . . . . . . . . . . . . . . . . . . . . . . . 299 . . . . . . . . . . Feeding criteria ....................................... 299 Choice and culture of foods . . . . . . . . . . . . . . . . . . . . . . 307 . . . . . . . . . General feeding practices . . . . . . . . . . . . . . . . . . . . . . . 336 . . . . . . . . . . Specific feeding practices ................................ 352 General methods used in our hatchery . . . . . . . . . . . . . . . . . 372 . . . . . . . Industrial-scale larval food processing in Italian hatcheries ......... 373 Summary ............................................ 374 9 Nutrition of Juvenile and Adult Fish ...................... 375 ............................. 375 Requirements and components Broodstock nutrition .................................... 407 Nutritional disorders .................................... 408 Environmental considerations . . . . . . . . . . . . . . . . . . . . . 411 . . . . . . . . . Feed studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411 . . . . . . . . . . . . Suggested feed formulas ................................. 460 Making and storing feeds ................................ 461 Feeding methods ...................................... 464 Summary ............................................ 467 10 Energetics ............................................ 469 Energy budget components and influencing factors . . . . . . . . . . . 469 . . . .

Almost a quarter of a century has elapsed since Cellular Biology of the Uterus, the predecessor of the present volume, was planned. During that period, especially in the decade since the publication of the last edition of Biology of the Uterus, new information in the field has been so voluminous as to require major revisions of most of the chapters, the addition of several new chapters, and the collaboration of a second editor to facilitate the selection of appropriate experts as authors. As in prior editions, a balance has been struck between classical biology and modem biochemistry and biophysics. The inclusion of basic histological and embryo logical information provides a necessary, though often lacking, background for the protein chemist and molecular biologist and a bridge between the cell biologist and clinician. Thus, major practical problems in human reproduction, such as the genesis of endometrial carcinoma and the cause of the initiation of labor, may be approached on a firm scientific footing. The current edition deals primarily with the biology of the uterus itself (comparative and human) rather than placentation or pregnancy and thus is a synthesis of data derived from many techniques, both conventional and modem. As it is clearly beyond the competence of anyone scientist to prepare such a text on the basis of personal knowledge and experience, the aid of 22 distinguished scientists was enlisted."

From the discovery of Pdx1, the first "master gene" of pancreatic development, to the most recent findings on the role of microRNAs in beta cell homeostasis, the last fifteen years have seen an unprecedented advance in our understanding of the precise development and organization of the many different cell types that make up the pancreas. It is now widely acknowledged that the therapeutic differentiation of stem cells into pancreatic cells is an ambitious endeavor that will not succeed without a thorough understanding of the molecular processes underlying the native development of the organ. This book, aimed at experts and students alike, offers a comprehensive review of the state of the art in both pancreatic development and regeneration. The many strategies to differentiate adult and embryonic stem cells into pancreatic beta cells are also discussed in the context of potential therapeutic interventions for type I diabetes.

Comparative endocrinology is one of the most rapidly developing subdis ciplines within the field of endocrinology, and it is having a significant impact on research at the molecular, cellular, organisma1 and environmental levels. Much of the current ferment in endocrinology is in reproductive endocrinology. The purpose of this volume on hormones and reproduction in fishes, amphibians and reptiles is to summarize our present understandings and to identify important research problems to be addressed in the area of comparative reproductive endocrinology. It was inspired by the gathering at Copper Mountain, Colorado, of eminent endocrine scientists from around the world on the occasion of the Tenth International Symposium on Comparative Endocrinology in July, 1985. While preparing for that meeting, we decided that a special volume on reproductive endocrinology was needed to summarize what is known and to stimulate research in particular directions. Why do we emphasize fishes, amphibians and reptiles? First, knowledge about the reproductive endocrinology of these ectothermic vertebrates can provide a clearer picture of the evolution of reproductive hormones and their effects on target organs. This comparative approach can lead to new theories about the evolution of reproductive control mechanisms. Second, studies concerning the reproductive endocrinology of "lower" vertebrates can result in development of "model systems" for application to studies of birds and mammals. Indeed, information about the patterns of reproductive control in ectothermic vertebrates can tell us which are evolutionarily stable and which are labile."

Cell signalling lies at the heart of many biological processes and currently is the focus of intense research interest. In multicellular organisms, it is central to how different types of cell communicate with each other and how they detect and respond to extracellular signals. Intercellular communication is vital to single-celled organisms as well, allowing them to respond to environmental cues and signals.

To date, much of the understanding of signalling mechanisms has come from research on specific cell types (eg mouse lymphocyte and cardiomyocyte) or on organisms in which communication systems such as nervous and endocrine systems are well established. This volume therefore aims to 'fill the gap' by concentrating on 'simple organisms' where the elements of those signalling systems first evolved. Many of the groups covered contain important pathogens or parasites, and the potential for manipulating signalling pathways for therapeutic intervention will be highlighted.

The present review covers a very neglected field in regeneration studies, namely, tissue and organ regeneration in reptiles, especially represented by the lizard model of regeneration. The term "regeneration" is intended here as "the ability of an adult organism to recover damaged or completely lost body parts or organs." The process of recovery is further termed "restitutive regeneration" when the lost part is reformed and capable of performing the complete or partial physiological activity performed by the original, lost body part. Lizards represent the only amniotes that at the same time show successful organ regeneration, in the tail, and organ failure, in the limb (Marcucci 1930a, b; Simpson 1961, 1970, 1983). This condition offers a unique opportunity to study at the same time mechanisms that in different regions of the same animal control the success or failure of regeneration. The lizard model is usually neglected in the literature despite the fact that the lizard is an amniote with a basic histological structure similar to that of mammals, and it is therefore a better model than the salamander (an a- mniote) model to investigate regeneration issues.

This book is a comprehensive synthesis of current knowledge about the influence of genetic or genomic material on developing body cells. Written by a leading developmental biologist, this book brings together a century of research on a wide range of questions. In particular, it focuses on the question of whether genetic changes are irreversible after somatic cell specialization has taken place during cell development. Providing a full historical survey of the development of nuclear transplantation in unicellular and multicellular organisms, the book has great value in the search for a genetic cure for cancer and other biomedical cellular disorders, some of which may be alleviated by inducing activation of dormant genes to restore health. Unique in scope, depth and clarity of presentation, "Genomic Potential of Differentiated Cells" stands as a major contribution to current knowledge in cell, developmental and molecular biology, and in eukaryotic genetics and biochemistry. It should serve students, researchers and clinicians alike.

Branching morphogenesis, the creation of branched structures in the body, is a key feature of animal and plant development. This book brings together, for the first time, expert researchers working on a variety of branching systems to present a state-of-the-art view of the mechanisms that control branching morphogenesis. Systems considered range from single cells, to blood vessel and drainage duct systems to entire body plans, and approaches range from observation through experiment to detailed biophysical modelling. The result is an integrated overview of branching.

The objectives of this volume are to present an up-to-date (literature survey up to 2001) account of the biology of Artemia focusing particularly upon the major advances in knowledge and understanding achieved in the last fifteen or so years and emphasising the operational and functional linkage between the biological phenomena described and the ability of this unusual animal to thrive in extreme environments. Artemia is a genus of anostracan crustaceans, popularly known as brine shrimps. These animals are inhabitants of saline environments which are too extreme for the many species which readily predate them if opportunity offers. They are, thus, effectively inhabitants of extreme (hypersaline) habitats, but at the same time are able to tolerate physiologically large changes in salinity, ionic composition, temperature and oxygen tension. Brine shrimp are gener ally thought of as tropical and subtropical, but are also found in regions where temperatures are very low for substantial periods such as Tibet, Siberia and the Atacama desert. They have, thus, great powers of adaptation and are of interest for this capacity alone. The earliest scientific reference to brine shrimp is in 1756, when Schlosser reported their existence in the saltpans of Lymington, England. These saltpans no longer exist and brine shrimp are not found in Britain today. Later, Linnaeus named the brine shrimp Cancer salinus and later still, Leach used the name Artemia salina. The strong effect which the salinity of the medium exerts on the morphological development of Artemia is now widely recognised."

This book is indispensable to researchers in fields as diverse as Molecular Biology and Biophysics. It covers the important role that mitochondria play in a variety of biochemical spheres. It analyses how mitochondria affect metabolic pathways, how they are active in the regulation of cytosolic constituents, and their role in initiating signal pathways. Also covered are the way mitochondria help to regulate apoptosis, and how they modulate cellular hypertrophy and proliferation. It gives an overview of the emergence of mitochondria as an important regulator of cell signaling, with a particular focus on their pathophysiology.

In September 2005 an International Meeting on "Targeted Therapies in Cancer: Myth or Reality" was held in Milan. This successful Meeting was intended to represent a forum for scientists and clinicians working in cancer drug discovery and therapy to share their reflections and experiences on how the paradigm shift from empiricism to molecular targeted therapies is contributing to the translation of basic knowledge into new therapies for cancer patients. This book collects the contributions given by scientists and clinicians, from Academia and Industry, who participated to this Meeting.

We hope that this book contributes to improve our approach to cancer drug discovery and, ultimately, to find new, more efficacious and better tolerated drugs for cancer patients. It provides an overview of diverse approaches ranging from drug discovery to cellular therapy. Although this change in paradigm has been useful, its entry into the clinical arena was associates with unforeseen problems including the emergence of resistance, unexpected side effects and failures. Time is therefore ripe for a critical cultural reflection on the state of the art, prospects and limitations. Ultimately, is targeted therapy in cancer a myth or a reality?

Lemurs: Ecology and Adaptation brings together information from recent research, and provides new insight into the study of lemur origins, and the ecology and adaptation of both extant and recently extinct lemurs. In addition, it addresses issues of primate behavioral ecology and how environment can play a major role in explaining species variation. Moreover, in a larger context, the information contained in this volume expands our knowledge of primate ecology and allows us further insight into mammalian adaptations to unusual and often harsh environmental conditions that arise from both natural and anthropogenic factors.

The book is divided into two sections. The first section is a background to lemurs and their ecology and it includes chapters on origins of lemurs, history of ecological studies on lemurs in Madagascar, theories relating to the evolution of lemur traits, and ecology of the recently extinct (sub-fossil) lemurs. Section two is comprised of chapters focusing on the ecology and adaptations of many species of extant lemurs to the diverse habitats found on Madagascar, and in some cases, adaptations to extreme climatic variability and natural disasters.

This volume covers aspects of ecology, behavior, genetics, taxonomy, 'cultural' patterns, hunting by non-human primates, physiology, dietary chemistry, and ecotourism, in several major clades of primates from galagos and pottos, through cercopithecoids, to hominoids.

This volume details the different ways that nocturnal primates avoid predators. It is a first of its kind within primatology, and is therefore the only work giving a broad overview of predation nocturnal primate predation theory in particular in the field

Additionally, the book incorporates several chapters on the theoretical advances that researchers studying nocturnal primates need to make.

The rapid advances in elucidating the biosynthesis and mode of action of the plant hormone ethylene, as well as its involvement in the regulation of the whole plant physiology, made imperative the organization of a series of dedicated conferences. This volume contains the main lectures and poster contributions presented at the 7th International Symposium on the Plant Hormone Ethylene held in Pisa in 2006.

Advanced biotechnologies enable breeders to produce a whole generation of new crops for specialist needs ("designer crops"), including raw materials for the energy, chemical and pharmaceutical industries. This book provides concerns useful to promote an increase of the productivity of crops by using functional genomics (to understand the regulation of plant metabolism at molecular, cellular and whole plants), and the improvement of photosynthetic efficiency (to design new plants with enhanced raw materials percent and recovery). Fundamental thematics have been addressed: metabolic engineering, plant breeding tools, renewable biomass for energy generation, fibres and composites, biopharmaceuticals. The gained know how is relevant to identify bottlenecks in the major production chains and to propose actions for moving these issues forward: in particular to; i) produce new compounds by expressing foreign heterologous genes; ii) modify pathways to influence quality and/or yield of existing indigenous molecules; iii) bioprocess plant or organic waste stream into value-added products. The chapters of this book have been written by experts from all around the world. Consequently, this book is expected to be of great interest to scientists, researchers, farmers, processors and retailers, but also to students, technocrats and planners interested in the progress made with the development of new industrial crops.

A presentation of all aspects of neural crest cell origins (embryological and evolutionary) development and evolution; neural crest cell behavior (migration) and anomalies (neurocristopathies and birth defects) that arise from defective neural crest development. The treatment of development will include discussions of cellular, molecular and genetic aspects of the differentiation and morphogenesis of neural crest cells and structures derived from neural crest cells. The origins of the neural crest in embryology will be discussed using the recent information on the molecular basis of the specification of the neural crest. Also presented are the advances in our understanding of the evolution of jaws from studies on lampreys and of the neural crest from studies on ascidians and amphioxus.

This timely work is a collection of papers presented at the XIth international congress of the International Association of Plant Tissue Culture & Biotechnology. It continues the tradition of the IAPTC&B in publishing the proceedings of its congresses. The work is an up-to-date report on the most significant advances in plant tissue culture and biotechnology as presented by leading international scientists. It will be crucial reading for agricultural scientists, among others.

Much of our knowledge of stem cells has been inferred from studies of remarkable few species. The ability to manipulate stem cells in "model" organisms such as the mouse and a few other vertebrate species has driven our understanding of basic biology of stem cells. The power and efficiency of studying model organisms, however, comes at a cost since a few species, obviously, do not reflect natures true diversity. Unfortunately, although all multicellular organisms seem to rely on stem cells, and although this seems to be a question of key importance for understanding the evolution of animal life, little is known about stem cells in early-branching taxa.

The book "Stem Cells: From Hydra to Man" illustrates that here is more than human and mouse stem cells to learn from. Reflecting an enormous growth in the knowledge of stem cells in various organisms, the book presents the conceptual language and the nature of questions, as well as a summary of the advances in our understanding of stem cells from a comparative point of view that has resulted from the development of new technology and the development of novel model organisms over the past few decades. As such this book is largely a horizon analysis of a frontier rather than a retrospective. It presents an integrative approach to animal stem cells and covers the major contributions, tools and trends in a newly emerging field: comparative stem cell biology.

Despite the tremendous diversity of the cells of the hematopoietic system, they are all derived from common precursor cells that are generated in the fetus and persist into adult life. In this regard, Band T lymphocytes, which comprise the two arms of the antigen-specific and inducible immune system, though functionally very different, are descendants of the same stem cell precursor. In the past several years, we have witnessed an explosion of information regarding the process by which differentiation of B-and T-cells from stem cells occurs. This information, like the answers to most important biological questions, has come from multiple and diverse directions. Because all hematopoietic cells arise from common precursors, complex regulatory processes must be involved in determining commitment to various lineages. Understanding commitment to the B- or T-cell lineage remains incomplete; however, identification of transcription factors necessary for progression along specific B-and T-cell pathways suggests that we are on the verge of understanding the molecules involved in the initial fate-determining steps. Studies of this type previously could be accomplished only in nonmammalian systems that are more amenable to genetic approaches. However, new technologies allow increasingly elegant and informative studies in mammalian systems, particularly for cells of the hematopoietic system.

In most respects, Abigail and Brittany Hensel are normal American twins. Born and raised in a small town, they enjoy a close relationship, though each has her own tastes and personality. But the Hensels also share a body. Their two heads sit side-by-side on a single torso, with two arms and two legs. They have not only survived, but have developed into athletic, graceful young women. And that, writes Mark S. Blumberg, opens an extraordinary window onto human development and evolution.
In Freaks of Nature, Blumberg turns a scientist's eye on the oddities of nature, showing how a subject once relegated to the sideshow can help explain some of the deepest complexities of biology. Why, for example, does a two-headed human so resemble a two-headed minnow? What we need to understand, Blumberg argues, is that anomalies are the natural products of development, and it is through developmental mechanisms that evolution works. Freaks of Nature induces a kind of intellectual vertigo as it upends our intuitive understanding of biology. What really is an anomaly? Why is a limbless human a "freak," but a limbless reptile-a snake-a successful variation?
What we see as deformities, Blumberg writes, are merely alternative paths for development, which challenge both the creature itself and our ability to fit it into our familiar categories. Rather than mere dead-ends, many anomalies prove surprisingly survivable-as in the case of the goat without forelimbs that learned to walk upright. Blumberg explains how such variations occur, and points to the success of the Hensel sisters and the goat as examples of the extraordinary flexibility inherent in individual development.
In taking seriously a subject that has often been shunned as discomfiting and embarrassing, Mark Blumberg sheds new light on how individuals-and entire species-develop, survive, and evolve.

How does death help us understand the living? Death is more than the last event of life; it is interwoven into our growth, development, protection against disease, and more. It influences the direction of entire species via the cycle of a lifespan, and it involves asking many fascinating questions. How do we differentiate between life and death, though? How do we know when a person, animal, or cell is really dead? How much grey area is there in the science? Why do we age? Can we do anything about it? Scientifically, there's much we can learn about a living thing from its cells. In all living things, cells seem to carry "death" gene programs. Some living organisms have created systems to use these to their own advantage. Humans, for example, use the death of specific cells to hone our immune system and to give us fingernails and hair. Perhaps the most dramatic use occurs during the metamorphosis of insects and frogs. Even single-celled organisms use "quorum sensing" to eliminate some cells to ensure the overall survival of their colony in harsh environments. Thus, there is more to death than just dying. This latest book from science writer Gary C. Howard ties together the many ways that death helps us understand life. He synthesizes the involvement and relation of cells, tissues, organisms, and populations, explaining what happens at the end of life. Between discussions about popular topics such as the ethics of extending life and cell regeneration, Howard also answers fascinating questions about life and death. The resulting book examines how the end of life is determined and what we can learn from this process.

The ability of striated muscle tissue to adapt to changes in activity or in working conditions is extremely high. In some ways it is comparable to the ability of the brain to learn. The interest in muscle adaptation is increasing in relation to the idea that physical fitness helps in the prevention of disease, may counteract the loss of physical performance and generally improves wellbeing. Plasticity is the word used since the late 1970a (TM)s to indicate collectively all the processes and mechanisms which form the background of muscle adaptation. This book aims to provide a systematic updating of the available knowledge on molecular and cellular mechanisms, as well as on changes at whole muscle level. The book means to be a guide and a help for people who enter the field as PhD or medical students, but is also a tool for refreshing and updating knowledge for people already active in the field in basic sciences as well as in applied disciplines such as neurology, sports science and rehabilitation.