Over the last twenty years there has been an explosive growth in our understanding of the molecular, cellular, and anatomical changes that occur in the days and weeks following brain injury. It is now clear that training and exposure to certain environments can modify and shape neuronal plasticity in lower animals and humans. In humans, in particular, there are new ways of charting neuronal plasticity at the ensemble or regional level using functional neuroimaging techniques such as positron emission tomography and functional magnetic resonance imaging. Thus, the time seems right for transporting the laboratory results to the clinic so that experimental findings can be tested in the "field." This volume provides some impetus to moving the field of cognitive neuroscience a little further in its efforts to improve the lives of patients who have suffered a debilitating brain injury.

Biomechanics has a distinguished history extending at least to the 16th Century. However the later half oftbis century has seen an explosion ofthe field with it being viewed as affering exciting challenges for physical scientists and engineers interested in the life sciences, and wonderful opportunities for life scientists eager to collaborate with physical scientists and engineers and to render their scientific work more fundamental. That the field is now weil established and expanding is demonstrated by the formation of a World Committee for Biomechanics and the success and large participation in the 1st and 2nd World Congresses of Biomechanics, held respectively in San Diego in 1990 and in Amsterdam in 1994. With more than 1350 scientific papers delivered at the 2nd World Congress, either within symposia or oral or poster sessions, it would have been out of the question to try to produce comprehensive edited proceedings. Moreover, we are confident that most of the papers have been or will be published in one ofthe excellentjoumals covering the field. But of effort contributed by the plenary lecturers and the tutorial we thought that the large amount and keynote speakers of various symposia deserved tobe recognised in the form of a specific publication, thus also allowing those unable to attend the presentatiops . . tC\ sh?r~ in the findings. Furthermore, we feel that there is now a need to review aspects 'oftlie freld.

Once Nietzsche said that human beings may be divided into two categories: Apollonians and Dionysians*. By this the philosopher meant that there are human beings a) who know what they are going to do in the long-term future (what we now call the grant application for the next 5 years), i. e. , Apollonians, and b) who barely know what they are going to do tomorrow morning before breakfast, i. e. , Dionysians. ** To organize a symposium, this symposium in particular, a committee had to be formed either of individuals sharing both Nietzschean characteristics or of individuals possessing either characteristic. Considering the rarity of the former type of subject, this organizing committee was spontaneously formed by a typical sample of both types of individuals. We first met in Perugia in 1988. Those of us who were Apollonians had thus a chance to organize a programme. The Dionysians knew what was going to happen to them, but, of course, did not know yet how to cope with it. They duly did so every day of the meeting, after breakfast. The organizers decided that it would be a useful exercise to assemble experts having different perspectives but all pursuing a very rapidly developing aspect of cell biology. They also hoped that these selected Apollonians and Dionysians would not merely recount their results but try to project the future through active interchanges of ideas and opinions with other attendees.

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.

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 extensively revised and expanded new edition offers concepts, principles and applied information that relates to the wellbeing of reptiles. As a manual on health and welfare in a similar vein to volumes addressing the sciences of anatomy, behaviour or psychology, this book thoroughly examines the biology of reptile welfare and is about meeting biological needs. The editors, acknowledged experts in their own right, have once again drawn together an extremely impressive international group of contributors. Positive and negative implications of general husbandry and research programs are discussed. In addition to greatly revised original content are nine new chapters offering readers novel insight into: * sensory systems * social behaviour * brain and cognition * controlled deprivation and enrichment * effects of captivity-imposed noise and light disturbance on welfare * spatial and thermal factors* evidential thresholds for species suitability in captivity * record keeping as an aid to captive care * arbitrary husbandry practices and misconceptions The authors have adopted a user-friendly writing style to accommodate a broad readership. Although primarily aimed at academic professionals, this comprehensive volume is fundamentally a biology book that will also inform all involved in captive reptile husbandry. Among others, zoo personnel, herpetologists, veterinarians, lab animal scientists, and expert readers in animal welfare and behavioural studies will benefit from this updated work.

Environmental conditions change considerably in the course of 24 h with respect to abiotic factors and intra- and interspecific interactions. These changes result in limited time windows of opportunity for animal activities and, hence, the question of when to do what is subject to fitness maximisation. This volume gives a current overview of theoretical considerations and empirical findings of activity patterns in small mammals, a group in which the energetic and ecological constraints are particularly severe and the diversity of activity patterns is particularly high. Following a comparative ecological approach, for the first time activity timing is consequently treated in terms of behavioural and evolutionary ecology, providing the conceptual framework for chronoecology as a new subdiscipline within behavioural ecology. An extensive Appendix gives an introduction to methods of activity modelling and to tools for statistical pattern analysis.

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.

(Chapters 11 to 14) summarise important features of the biological clock at the level of whole animal covering all vertebrate classes (fish to mammal). Chapters 15 and 16 are on long term (seasonal) rhythms in plants and higher vertebrates. Short term rhythms (ultradian rhythms), the significance of having a clock system in animals living in extreme (arctic) environments, and the diversity of circadian responses to melatonin, the key endocrine element involved in regulation of biological rhythms, have been discussed in Chapters 17 to 19. Finally, a chapter on sensitivity to light of the photoperiodic clock is added which, using vertebrate examples, illustrates the importance of wavelength and intensity of light on circadian and non-circadian functions. A well-known expert writes each chapter. When presenting information, the text provides consistent thematic coverage and feeling for the methods of investigation. Reference citation within the body of the text adequately reflects the literature as subject is developed. A chapter begins with an abstract that enables a reader to know at the first glance the important points covered in that chapter. The chapter concludes with a full citation of references included in the text, which could be useful for further reading. The book ends with a comprehensive subject index that may be useful for quick searches.

The annual Congress of the Italian Biochemical and Molecular Biology Society (SIB) was held in September 1999 in Alghero, Sardegna, Italy. The programme envisaged a symposium on molecular adaptations of haemoglobin function in ver- tebrates. Haemoglobin specialists from several countries were invited to speak at the symposium and paved the way for wide-ranging and stimulating discussions. The symposium contributions have been collected together in this volume. The structure/function relationship in haemoglobins from vertebrates (fishes populat- ing temperate and polar environments, diving birds, marine and terrestrial mam- mals) has been tackled from many angles, focusing on the adaptation of the oxy- gen-transport system to the constraints dictated by the environment. Eleven arti- cles review some of the most recent developments of the studies on this ancient oxygen-transport protein, characterized by high conservation during evolution. The volume offers the reader an updated, state-of-the-art summary of a field that is enjoying a true renaissance. Covering the topic from several viewpoints, the volume includes protein chemistry (amino acid sequence, secondary, tertiary and quaternary structures, thermodynamics of oxygen-binding features), molecular biology (globin gene structure, sequence, organization, expression and regulation) and evolution. In this representation of effective multidisciplinary and multina- tional collaborative efforts, reference is available to a wide range of disciplines and biological systems. The tools of the investigators comprise advanced and powerful methodologies developed in recent years, e. g.

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.

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 book is a compilation of the lectures and oral and poster communications presented at the Advanced Study. Institute on "Vascular Endothelium: Physiological Basis of Clinical Problems II," which took place between June 20 and 30, 1992 in Rhodes, Greece. This third in a series of ASIs on vascular endothelium continued on the theme of the first (1988) ASI on "Receptors and Transduction Mechanisms" and particularly expanded that of the 1990 conference on ''Physiological Basis of Clinical Problems. " We continued the successful practice of bringing together clinicians and scientists: this was reflected equally well in the composition of the organizing committee as in the background of the particiJ?ants. Endothelial cell functions and dysfunctions present as many challenges to the mvestigator as they do to the curious clinical practitioner. As these problems are necessarily different, this unique ten-day co-habitation of these individuals continued to offer fresh outlooks to each, stimulated potential collaborative efforts and, most importantly, advanced --ever so slightly--our knowledge of vascular biology. This year's conference was further enriched by the presence of several of our colleagues from Eastern Europe whom we are delighted to welcome as officially sponsored participants to this and future NATO-supported meetings. It is never superfluous to remind readers and participants that those signing at the bottom of this page, while responsible for many of the ASI's and the book's deficiencies, are but three of the many contributors to the successes.

Throughout history, hearing and sound perception have been typically framed in the context of how sound conveys information and how that information influences the listener. "Hear Where We Are" inverts this premise and examines how humans and other hearing animals use sound to establish acoustical relationships with their surroundings. This simple inversion reveals a panoply of possibilities by which we can re-evaluate how hearing animals use, produce, and perceive sound. Nuance in vocalizations become signals of enticement or boundary setting; silence becomes a field ripe in auditory possibilities; predator/prey relationships are infused with acoustic deception, and sounds that have been considered territorial cues become the fabric of cooperative acoustical communities. This inversion also expands the context of sound perception into a larger perspective that centers on biological adaptation within acoustic habitats. Here, the rapid synchronized flight patterns of flocking birds and the tight maneuvering of schooling fish becomes an acoustic engagement. Likewise, when stridulating crickets synchronize their summer evening chirrups, it has more to do with the 'cricket community' monitoring their collective boundaries rather than individual crickets establishing 'personal' territory or breeding fitness. In "Hear Where We Are" the author continuously challenges many of the bio-acoustic orthodoxies, reframing the entire inquiry into sound perception and communication. By moving beyond our common assumptions, many of the mysteries of acoustical behavior become revealed, exposing a fresh and fertile panorama of acoustical experience and adaptation.

The study of primate locomotion is a unique discipline that by its nature is interdis ciplinary, drawing on and integrating research from ethology, ecology, comparative anat omy, physiology, biomechanics, paleontology, etc. When combined and focused on particular problems this diversity of approaches permits unparalleled insight into critical aspects of our evolutionary past and into a major component of the behavioral repertoire of all animals. Unfortunately, because of the structure of academia, integration of these different approaches is a rare phenomenon. For instance, papers on primate behavior tend to be published in separate specialist journals and read by subgroups of anthropologists and zoologists, thus precluding critical syntheses. In the spring of 1995 we overcame this compartmentalization by organizing a con ference that brought together experts with many different perspectives on primate locomo tion to address the current state of the field and to consider where we go from here. The conference, Primate Locomotion-1995, took place thirty years after the pioneering confer ence on the same topic that was convened by the late Warren G. Kinzey at Davis in 1965."

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 Office of Health and Environmental Research (OHER) has supported and continues to support development of computational approaches in biology and medicine. OHER's Radiological and Chemical Physics Program initiated development of computational approaches to determine the effects produced by radiation of different quality (such as high energy electrons, protons, helium and other heavy ions, etc. ) in a variety of materials of biological interest-such as water, polymers and DNA; these include molecular excitations and sub-excitations and the production of ionization and their spatial and temporal distribution. In the past several years, significant advances have been made in computational methods for this purpose. In particular, codes based on Monte Carlo techniques have .been developed that provide a realistic description of track-structure produced by charged particles. In addition, the codes have become sufficiently sophisticated so that it is now possible to calculate the spatial and temporal distribution of energy deposition patterns in small volumes of subnanometer and nanometer dimensions. These dimensions or resolution levels are relevant for our understanding of mechanisms at the molecular level by which radiations affect biological systems. Since the Monte Carlo track structure codes for use in radiation chemistry and radiation biology are still in the developmental stage, a number of investigators have been exploring different strategies for improving these codes."

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.

A number of factors have come together in the last couple of decades to define the emerging interdisciplinary field of structural molecular biology. First, there has been the considerable growth in our ability to obtain atomic-resolution structural data for biological molecules in general, and proteins in particular. This is a result of advances in technique, both in x-ray crystallography, driven by the development of electronic detectors and of synchrotron radiation x-ray sources, and by the development ofNMR techniques which allow for inference of a three-dimensional structure of a protein in solution. Second, there has been the enormous development of techniques in DNA engineering which makes it possible to isolate and clone specific molecules of interest in sufficient quantities to enable structural measurements. In addition, the ability to mutate a given amino acid sequence at will has led to a new branch of biochemistry in which quantitative measurements can be made assessing the influence of a given amino acid on the function of a biological molecule. A third factor, resulting from the exponential increase in computing power available to researchers, has been the emergence of a growing body of people who can take the structural data and use it to build atomic-scale models of biomolecules in order to try and simulate their motions in an aqueous environment, thus helping to provide answers to one of the most basic questions of molecular biology: the relation of structure to function.

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."

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.