This book presents the latest in mammary gland transgenesis, the exploitation of transgenic technology for the production of therapeutic proteins by routine or conventional methods. Following a section with an overview of all relevant methodologies, readers will find relevant information on the regulation of milk gene expression and bioreactor species such as cattle, rabbits and pigs.

This book deals with information processing in the primate temporal visual cortex, one of the higher visual association areas, which is believed to be important for the representation of complex stimuli and may also play a role in visual memory. Here, the need for rapid information processing shapes the functional architecture of all sensory systems, acting to reduce, where possible, wiring length and the number of synapses, to allow faster processing.

In the last two decades, our knowledge on regulatory peptides and their cognate receptors, most of which are members of the seven transmembrane receptor families, has increased enormously. Regulatory peptides are small proteins which, besides their hormonal functions in regulating cellular metabolism in various tissues, may also act as neurotransmitters, and thus they often carry the prefix "neuro." Many of the cognate receptors involved in transducing the peptidergic signal across the cell membrane via a family of G proteins exist in multiple forms, the number of which frequently exceeds that of the corresponding peptide ligands. In this book, various peptide-receptor systems are discussed, e.g. CRF, somatostatin, TRH, opioid peptides, vasopressin, and oxytocin. It also discusses new strategies such as "reverse physiology" to uncover new peptides and orphan receptors.

The scientific contribution of Mike Bradbury to the study of the blood-brain barrier is considerable and wide-ranging, starting with his M.D. thesis in 1962 and still continuing today. The varied spectrum of topics relating to the blood-brain barrier presented in this volume and the many geographical locations from which both speakers and participants gathered to attend the symposium are a fitting testament both to Mike's wide-spread influence in the field and to the esteem in which he is held. When we first had the idea of afestschrift to mark Mike's retirement as Professor of Physiology at King's College London and the beginning of a new vie libre as scientist and yachtsman the plan was initially for a gathering of all of the many colleagues, collaborators and students who had worked with him over the years. However what we had not taken into account was the closeness of the international community of workers in the field, the widespread influence that Mike had wielded and the speed with which word would spread. We should have anticipated all three. The final outcome was an excellent symposium with the majority of the world's key workers either contributing or attending. We hope that this volume presents an adequate record of the meeting.

Volume II features a variety of animal and human prion diseases, including the newly-identified atypical forms of bovine spongiform encephalopathy and scrapie in animals, and variably protease-sensitive prionopathy in humans, prions in the environment, Tau pathology in human prion disease, transmission of the disease by blood transfusion, mammalian and non-mammalian models, conventional and advanced diagnoses, prion-specific antibodies, as well as decontamination of prions and development of therapeutics of prion diseases, such as the application of immunomodulation. This volume provides up-to-date knowledge about the etiology, pathogenesis, classification, histopathological, and clinical aspects of the highly publicized animal and human prion diseases.

The book begins by describing in detail the mechanisms of energy exchange - radiative, convective, conductive and evaporative - together with techniques for their determination. The discussion extends to the importance of CO2, ozone and methane, together with that of aerosol pollutants and the evolution of atmospheric CO2. Subsequent chapters apply the results of the biophysical methods to mammals, birds and aquatic animals. Discussion includes problems of shelter and shade for animals in tropical environments and techniques for the thermal evaluation for shelters and for several tree types. The details of heat exchange between animals and the environment are presented, in separate chapters covering Mammals and Birds and Aquatic Mammals. A chapter on Shade and Shelter describes the importance of shade for animals, factors of shade efficiency, the protections offered by shelter and methods of calculating the protection afforded by both shade and shelter. A Special Methods chapter offers a variety of techniques for evaluating cutaneous and respiratory evaporation, and practical methods for sampling of hairs and the evaluation of hair coat characteristics.

Adult and immature nervous system are capable of considerable "plasticity" and unravelling the underlying mechanisms is one of the principal and most fascinating goals of Neurobiology. A major contribution to our understanding of neural plasticity has come from recent studies in excitato- ry amino acids - which are thought to mediate a large part of the excitatory synaptic transmission on the brain. Important steps in this explosive field are: 1) the synthesis of relatively specific antagonists of the N-methyl-D aspartate (NMDA) and non-NMDA receptors subtypes, 2) the characterization of the unique features of the NMDA receptor channel complex notably its voltage dependent Mg++ blockade, its permeability to calcium and its allosteric modulation by glycine, 3) the demonstration that by virtue of their Ca++ permeability NMDA receptors are involved in many -but not all -synapses in the initiation but not the maintennce of long term potentiation (L TP) an experimented model of learning and memory processes. More recent studies also indicate tha excitatory amino acids also play an important role in developmental plasticity in vivo; in cell cultures low levels of excitatory amino acids have trophic roles and can inhibit or promote neurite growth. Excitatory amino acids also play an important role also in other forms of neural plasticity such as the use dependent permanent changes in neural circuit produced by brief seizures (epileptogenesis) as well as the reactive sprouting and neosynapse formation which take place in epilepsy models and after deafferentiation or lesions.

This book represents the proceedings of a NATO Advanced Research Workshop of the same name, held at St. Andrews University, Scotland in July of 1989. It was the first meeting of its kind and was convened as a forum to review and discuss the phylogeny of some of the cell biological functions that underlie nervous system function, such matters as intercellular communication in diverse, lower organisms, and the electrical excitability of protozoans and cnidarians, to mention but two. The rationale behind such work has not necessarily been to understand how the first nervous systems evolved; many of the animals in question provide excellent opportunities for examining general questions that are unapproachable in the more complex nervous systems of higher animals. Nevertheless, a curiosity about nervous system evolution has invariably pervaded much of the work. The return on this effort has been mixed, depending to a large extent on the usefulness of the preparation under examination. For example, work on cnidarians, to many the keystone phylum in nervous system evolution simply because they possess the "first" nervous systems, lagged behind that carried out on protozoans, because the latter are large, single cells and, thus, far more amenable to microelectrode-based recording techniques. Furthermore, protozoans can be cultured easily and are more amenable to genetic and molecular analyses.

This fully-revised new edition of the best-selling Equine Clinical Medicine, Surgery and Reproduction is supported by over 1800 illustrations of the highest quality: colour photographs, diagnostic images including MRI and CT, and diagrams. System-based, the chapters introduce each individual system with precise information on the relevant basic anatomy and physiology, standard clinical examination techniques and useful differential diagnostic aids. This is followed by diseases and disorders that are pertinent to that system, grouped together either anatomically or based on presenting clinical signs. Each condition is described using consistent headings: definition/overview, etiology and pathophysiology, clinical presentation, diagnosis, differential diagnoses, management/treatment, and prognosis. Additional chapters deal with the foal and wounds. New to the second edition: - All chapters are updated throughout - Additional chapters on the axial musculoskeletal system (neck, back and pelvis) and muscle diseases and problems - A whole new section on soft tissue injuries of the foot - More information on diagnostic tests including over-ground endoscopy, chest and liver ultrasonography, head CT, and foot MRI - Material on equine dentistry, neurology, endocrine system, the foal, and the liver has been considerably expanded - All illustrations and photographs have been reviewed and many replaced with higher quality images. The focus throughout remains on providing clinically relevant information required for practical case management, plus sufficient background on causes and disease processes to enable readers to understand the conditions and the rationale for diagnostic and treatment options. An international group of respected clinicians have come together under the editorship of Dr Graham Munroe to create a textbook that will be of lasting value as a teaching and training resource for equine clinical teachers and their students in veterinary medicine and related equine courses, as well as a ready reference for non-specialist mixed or equine clinical practitioners

Our purposes in this preface are, first, to reiterate our view of Current Ornithology's role; second, to describe briefly the contents of this vol ume; and third, to acknowledge the generous help of our Editorial Board and of the reviewers we have consulted about the contents of Volumes 13 and 14. As far as we know, Current Ornithology is the only English-lan guage publication currently devoted exclusively to extensive reviews and syntheses of topics pertaining to all aspects of the biology of birds. Its chapters deal with subjects falling under such diverse rubrics as ecology, evolution, behavior, phylogeny, behavioral ecology, anatomy and physiology, and conservation biology, but all focus primarily on birds. Its authors, whether members of the National Academy or young investigators just beginning their careers, are leading authorities on their subjects, and its referees are selected for their knowledge and expertise in the topics covered by the chapters they are asked to review.

The body of any animal can be viewed as a society or ecosystem whose individual members are cells, reproducing by cell division and organized into collaborative assemblies or tissues. In this ecosystem, the cells are born, live and die under various forms of selection pressure such as territorial limitation, population size, source of nutrients provided, infectious agents, etc. The body is a highly organized society of cells whose main task is the maintenance of homeostasis of the whole organism. The failure of control mechanisms which make the cell the unit of society, marking the beginning of its asocial behaviour, is most frequently a malignant alteration. This process is not abrupt, nor is it based on a single event. It is, rather, a long-term process characterized mainly by mutation, competition and natural selection operating within the population of cells. The basic mechanisms controlling the cell sociability represent the first defence line against the altered cells, while the second line of defence is supposed to be made up of the immune system cells.Speaking in Darwinian terms, within the ecosystem of an organism, cells of the immune system operate as predators of the altered and mutated cells or cells infected by the intracellular parasites. The biological phenomena whose mechanisms are, at present, explored and largely understood, certainly had their own evolution. Searching for the origin and details of the evolution of advanced solutions as well as selection pressures that might justify their emergence and existence, we often fail to see that many such phenomena are, in fact, co-evolutionary by-products of evolutionary innovations. In other words, the evolutionary emergence of advanced solutions is sometimes, if not always, accompanied by certain by-products and by the co-evolution of compensatory mechanisms acting as a counterbalance to these. An example of the evolution of advanced solutions is the evolution of adoptive immunity, and co-evolution of auto-immunity and alloimmunity. Alongside the diversification of the mechanisms of adoptive immunity, auto-immunity and alloimmunity gain attributes of the evolutionary by-products and become sources of selection pressure.To that effect, alloimmunity could be a source of very strong selection pressure in mammals, simply because it is directly connected with the reproductive efficacy. At the same time, new forms of selection pressure that are connected with adoptive immunity gave rise to new mechanisms controlling killer machinery of the immune system. Finally, the last in a line of by-products in the processes of evolutionary modelling and re-modelling of vertebrate immune systems can be regarded as the failure of anti-tumor immunity. There is now much evidence that tumors can be immunogenic. Tumor cells very often express antigens in a form recognizable by the host immune system, but most frequently without consequences on tumor progression. This has been shown in many experimental models and different experimental conditions. Immediate mechanisms for the escape of tumors from the immune response are very similar to mechanisms for the escape of the fetoplacental unit (as allograft) from the maternal immune response. The similarity between these two mechanisms is so significant that any randomness must be banished.Mechanisms of anti-tumor immunity in mammals are probably substantially different from mechanisms of anti-tumor immunity in other classes of vertebrates. Moreover, the type of most frequent tumors in non-mammalian vertebrates is also significantly different. Finally, the incidence of malignant tumors in non-mammalian vertebrates is significantly lower than the incidence of malignant tumors in mammals. These facts indicate that the mammalian immune system during the anti-tumor immune response is tricked by the similarity between tumor cells and trophoblast or other placental cells. From this aspect, anti-tumor immunity failure in mammals can be defined as an immunoreproductive phenomenon, which is developed under the evolutionary pressure of auto-immunity and alloimmunity/reproductive effectiveness. It may be a specific evolutionary approach in the rendering of anti-tumor immunity failure in mammals, and a new possibility for anti-tumor immunotherapy.

For out of olde hokes, in good feyth, Cometh all this newe science that men lere. Geoffrey Chaucer The Parliament of Fowls During the past two decades knowledge of the human menstrual cycle and of normal and abnormal reproduc- tive function has increased at a dramatic rate. As rec- ognized in this volume, this explosion of knowledge is due in large measure to the development of radio- immunoassays for the measurement of the minute quantities of reproductive hormones found in the cir- culation. Yet the foundations for the many recent developments were laid well in advance. The concepts and hypotheses tested were often suggested even be- fore the hormones involved were identified and iso- lated. A consideration of the historic aspects of re- search in this field places recent research in the appropriate perspective. Moreover, as presented by Drs. vii viii FOREWORD Gruhn and Kazer, the history of progress in this field makes fascinating reading. A review of the history of reproductive endocri- nology should be required reading for all students of the subject and reproductive endocrinologists in train- ing. Dr. Griff T. Ross, a noted reproductive endocri- nologist, often instructed his students that every hy- pothesis he tested could be found in some form in the publications of previous scientists. The answers to present and future questions are often hidden in the lessons of the past.

Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology."

'Further establishes the reputation of the series...an invaluable resource.' -Trends in Pharmacological Sciences, from a review of Volume 3 Volume 4 explores such emergent topics as: three-dimensional conceptions of ion channel proteins based on the available structural and functional data; the structure, pharmacology, and regulation of the GABAA receptors; and the Ca2+-dependent K+ channels in adrenal chromatic cell membranes.

Scientific advances over the past two decades have afforded unprecedented oppor tunities to understand the structure and function of receptors, receptor-ligand interactions, and receptor signaling. The extent ofprogress in this area is underscored by the recent Nobel Prize for Medicine and Physiology to Alfred Gilman and Martin Rodbell, both of whose work in understanding receptorlG-protein interactions has redefined the way in which we think of how hormones and neurochemicals exert their activity on cellular function. This book is replete with examples of current research approaches to help us better understand the cellular roles in which the renin-angiotensin system and the angiotensin receptors participate. Clearly, defining the structure of angiotensin receptor subtypes is an important first step in cJarifying the mechanisms by which these receptors take part in cellular function. However, the chapters within this book range far beyond structural studies and encompass research on tissue specific expression of the angiotensin receptor subtypes, the genetic regulation ofthese receptors, and the unique function ofvarious angiotensin subtypes in different organ systems, such as the brain, the reproductive system, adipose tissue, the heart, and the kidneys."

The following are the proceedings of the Third International Workshop on Perception held in Pavia, Italy, on September 27-30, 1993, under the auspices of four institutions: the Group of Cybernetic and Biophysics (GNCB)s of the National Research Council (CNR), the Italian Association for Artificial Intelligence (AI * IA), the Italian Association of Psychology (AlP), and the Italian Chapter of the International Association for Pattern Recognition (IAPR). The theme of this third workshop was: "Human and Machine Vision: Analogies and Divergencies." A wide spectrum of topics was covered, ranging from neurophysiology, to computer architecture, to psychology, to image understanding, etc. For this reason the structure of this workshop was quite different from those of the first two held in Parma (1991), and Trieste (1992). This time the workshop was composed of just eight modules, each one consisting of two invited lectures (dealing with vision in nature and machines, respectively) and a common panel discussion (including the two lecturers and three invited panellists).

Themonographisdevotedtothetheoreticalstudiesofradiationeffectsonmammals. It summarizes the results obtained by the author over the past 30 years, most of them being of high priority. In the course of these studies, a single approach to the modeling of radiation effects on mammals has been elaborated. Speci?cally, in the framework of the developed deterministic mathematical models, the effects of both acute and chronic irradiation in a wide range of doses and dose rates on vital body systems (hematopoiesis, small intestine, and humoral immunity), as well as on the development of autoimmune diseases, are investigated. The radiation effects on the mortality dynamics in homogeneous and nonhomogeneous(in radiosensitivity) mammalian populations are also studied by making use of the developed stochastic models. The most appealing feature of these mortality models consists of the fact that they account for the intrinsic properties of the exposed organism. Namely, within these models the stochastic biometrical functions are calculated proceeding from statistical characteristics and dynamics of the respective critical body system (hematopoiesis or small intestine). The performed theoretical investigations contribute to the development of the system and quantitative approaches in radiation biology and ecology. These studies elucidate the major regulatory mechanisms of the damage and recovery processes running in the vital body systems of exposed mammals and reveal the key par- eters characterizing the processes.

Signaling through antigen receptor initiates a complex series of events resulting in the activation of genes that regulate the development, proliferation and differentiation of lymphocytes. During the past few years, rapid progress has been made in understanding the molecular basis of signaling pathways mediated by antigen and cytokine receptors. These pathways involve protein tyrosine kinases which are coupled to downstream regulatory molecules, including small guanine nucleotide binding proteins (e. g. p21'OS), serine threonine kinases (e. g. , members of the ERK family), and a large group of transcription factors. More recently, there have been breakthroughs in elucidating the genetic defects underlying three X-linked primary immunodeficiency diseases in humans. This volume surveys aspects of these rapidly developing areas of research. The book is divided into 5 different sections. Section I deals with signaling pathways in B lymphocytes. It includes a contemporary assessment of B cell antigen receptor structures, and discussion of the role of Ig-a/lg-B polypeptides in linking the antigen receptor to intracellular signal transduction pathways. The role of accessory molecules in the regulation of signaling by the B cell antigen receptor is also considered. Section II adopts a similar approach to the analysis of the antigen receptor on T lymphocytes. The importance of specialized signaling motifs in the CD3 polypeptides, mechanisms whereby these motifs may interact with the lymphocyte-specific protein tyrosine kinases, and the downstream consequences of these interactions are reviewed. In addition, the role of antigen-induced apoptosis in the generation of immunological tolerance is discussed.

Proteins are still gaining importance in the pharmaceutical world, where they are used to improve our arsenal of therapeutic drugs and vaccines and as diagnostic tools. Proteins are different from "traditional" low-molecular-weight drugs. As a group, they exhibit a number of biopharmaceutical and formulation problems. These problems have drawn considerable interest from both industrial and aca demic environments, forcing pharmaceutical scientists to explore a domain previ ously examined only by peptide and protein chemists. Biopharmaceutical aspects of proteins, e.g., low oral bioavailability, have been extensively investigated. Although all possible conventional routes of ad ministration have been examined for proteins, no real, generally applicable alter native to parenteral administration in order to achieve systemic effects has yet been discovered. Several of these biopharmaceutical options have been discussed in Volume 4 of this series, Biological Barriers to Protein Delivery. Proteins are composed of many amino acids, several of which are notorious for their chemical instability. Rational design of formulations that optimize the native structure and/or bioactivity of a protein is therefore of great importance when long shelf life is required, as it is for pharmaceutical products. This issue has also been examined in two prior volumes of this series: Volume 2: Stability of Protein Pharmaceuticals (Part A) and Volume 5: Stability and Characterization of Protein and Peptide Drugs.

Mechanical stress is vital to the functioning of the body, especially for tissues such as bone, muscle, heart, and vessels. It is well known that astronauts and bedridden patients suffer muscle and bone loss from lack of use. Even the heart, in pumping blood, causes mechanical stress to itself and to vascular tissue. With the loss of mechanical stress, homeostasis becomes impaired and leads to pathological conditions such as osteopenia, muscle atrophy, and vascular tissue dysfunction. In elderly populations, such mechanical pathophysiology, as well as the mechanical activities of locomotor and cardiovascular systems, is important because skeletal and heart functions decline and cause diseases in other organs. In this monograph, mechanical stress is discussed by experts in the field with respect to molecular, cellular, and tissue aspects in relation to medicine. Covering topics such as gravity and tissues and disuse osteoporosis, the book provides the most up-to-date information on cutting-edge advancements in the field of mechanobiology and is a timely contribution to research into locomotor and circulatory diseases that are major problems in contemporary society.

As we approach the twenty-first century the problems of industrialization are evident: we find there is a greenhouse effect, the ozone layer is being depleted, the rain is acidified, and there is a terrible problem of increasing C0 concentrations in the atmo 2 sphere. The carbonic anhydrases are a unique family of enzymes that solve these problems in the human body: they are responsible for converting C0 (a gas) to 2 HC0-, which is the biggest intracellular buffer, with a concomitant decrease in a 3 hydroxyl ion. Globally, the functions of the carbonic anhydrases in photosynthesis in rain forests and in the algae and plankton that cover our oceans indicate that they are also of utmost importance in the maintenance of the acid-base balance on our planet. Although the whole field of C0 metabolism is enormous and still rapidly 2 expanding, because of the research interests of the editors this book is mainly concerned with mammalian carbonic anhydrases. However, if the interested reader intends to purify carbonic anhydrases from nonmammalian sources, Dr. Cheg widden has provided the necessary information in Chapter 7. The carbonic anhydrases were first discovered in 1933; until1976 there were thought to be only two isozymes. Since then CA ill, IY, V, VI, and Vll have been discovered and well characterized. There is, of course, no reason to believe that we have found them all."

The predecessor to this book was A Guide to the Laboratory Use of the Squid Loligo pealei published by the Marine Biological Laboratory, Woods Hole, Massachusetts in 1974. The revision of this long out of date guide, with the approval of the Marine Biological Laboratory, is an attempt to introduce students and researchers to the cephalopods and particularly the squid as an object of biological research. Therefore, we have decided to expand on its original theme, which was to present important practical aspects for using the squid as experimental animals. There are twenty two chapters instead of the original eight. The material in the original eight chapters has been completely revised. Since more than one method can be used for accomplishing a given task, some duplication of methods was considered desirable in the various chapters. Thus, the methodology can be chosen which is best suited for each reader's requirements. Each subject also contains a mini-review which can serve as an introduction to the various topics. Thus, the volume is not just a laboratory manual, but can also be used as an introduction to squid biology. The book is intended for laboratory technicians, advanced undergraduate students, graduate students, researchers, and all others who want to learn the purpose, methods, and techniques of using squid as experimental animals. This is the reason why the name has been changed to its present title. Preceding the chapters is a list of many of the abbreviations, prefixes, and suffixes used in this volume.

Here is the first effort in a single volume to cover all of the integrative functions of calcium signalling - how changes in intracellular calcium coordinate a variety of coherent cellular responses. Written by a team of internationally established researchers, Integrative Aspects of Calcium Signalling provides the latest experimental data and concepts, bringing together a detailed analysis of the events, processes, and functions regulated by calcium signalling. A unique resource for professionals and students of physiology, biophysics, neurobiology, biochemistry, and all related fields.

How does the brain code and process incoming information, how does it recog nize a certain object, how does a certain Gestalt come into our awareness? One of the key issues to conscious realization of an object, of a Gestalt is the attention de voted to the corresponding sensory input which evokes the neural pattern underly ing the Gestalt. This requires that the attention be devoted to one set of objects at a time. However, the attention may be switched quickly between different objects or ongoing input processes. It is to be expected that such mechanisms are reflected in the neural dynamics: Neurons or neuronal assemblies which pertain to one object may fire, possibly in rapid bursts at a time. Such firing bursts may enhance the synaptic strength in the corresponding cell assembly and thereby form the substrate of short-term memory. However, we may well become aware of two different objects at a time. How can we avoid that the firing patterns which may relate to say a certain type of move ment (columns in V5) or to a color (V 4) of one object do not become mixed with those of another object? Such a blend may only happen if the presentation times be come very short (below 20-30 ms). One possibility is that neurons pertaining to one cell assembly fire syn chronously. Then different cell assemblies firing at different rates may code different information."