This book provides a comprehensive, up-to-date review of the distribution, pharmacology and physiology of central 5-hydroxytryptamine (5-HT)4 receptors. The 5-HT receptor subtypes exhibit a unique pharmacology, distribution and function, of which the 5-HT4 receptor has been one of the most intensively studied in recent years, both from a basic research standpoint and as a target for novel therapeutics.

Twenty five years ago, Bill Stebbins presented the principles of animal psychophysics in an edited volume (Stebbins, 1970) describing an array of modem, creative methodologies for investigating the range of sensory systems in a variety of vertebrate species. These principles included precise stimulus control, a well defined behavioral response, and a rigorous behavioral procedure appropriate to the organism under study. As a generation of comparative sensory scientists applied these principles, our knowledge of sensory and perceptual function in a wide range of animal species has grown dramatically, especially in the field of hearing. Comparative psychoacoustics, i. e. , the study of the hearing capabilities in animals using behavioral methods, is an area of animal psychophysics that has seen remarkable advances in methodology over the past 25 years. Acoustic stimuli are now routinely generated using digital methods providing the researcher with unprecedented possibilities for stimulus control and experimental design. The strategies and paradigms for data collection and analysis are becoming more refined as well, again due in large part to the widespread use of computers. In this volume, the reader will find a modem array of strategies designed to measure detection and discrimination of both simple and complex acoustic stimuli as well experimental designs to assess how organisms perceive, identify and classify acoustic stimuli. Refinements in modem methodologies now make it possible to compare diverse species tested under similar, if not identical, experimental conditions.

Current Ornithology publishes authoritative, up-to-date, scholarly reviews of topics selected from the full range of current research in avian biology. Topics cover the spectrum from the molecular level of organization to population biology and community ecology. The series seeks especially to review (1) fields in which an abundant recent literature will benefit from synthesis and organization, or (2) newly emerging fields that are gaining recognition as the result of recent discoveries or shifts in perspective, or (3) fields in which students of vertebrates may benefit from comparisons of birds with other classes. All chapters are invited, and authors are chosen for their leadership in the subjects under review.

Muscle contraction has been the focus of scientific investigation for more than two centuries, and major discoveries have changed the field over the years. Early in the twentieth century, Fenn (1924, 1923) showed that the total energy liberated during a contraction (heat + work) was increased when the muscle was allowed to shorten and perform work. The result implied that chemical reactions during contractions were load-dependent. The observation underlying the "Fenn effect" was taken to a greater extent when Hill (1938) published a pivotal study showing in details the relation between heat production and the amount of muscle shortening, providing investigators with the force-velocity relation for skeletal muscles. Subsequently, two papers paved the way for the current paradigm in the field of muscle contraction. Huxley and Niedergerke (1954), and Huxley and Hanson (1954) showed that the width of the A-bands did not change during muscle stretch or activation. Contraction, previously believed to be caused by shortening of muscle filaments, was associated with sliding of the thick and thin filaments. These studies were followed by the classic paper by Huxley (1957), in which he conceptualized for the first time the cross-bridge theory; filament sliding was driven by the cyclical interactions of myosin heads (cross-bridges) with actin. The original cross-bridge theory has been revised over the years but the basic features have remained mostly intact. It now influences studies performed with molecular motors responsible for tasks as diverse as muscle contraction, cell division and vesicle transport.

by G. MILAZZO and M. BLANK This book contains the lectures of the fourth advanced course Bioelectrochemislry W Neroe-Muscle Function: Bioelectrochemistry, Mechanisms, Energetics and Contro~ which took place at the Majorana Center in Erice, Italy, October 20th to November 1, 1991. The scope of the course was international in terms of both sponsorship and partici pation. Sponsors included the Bioelectrochemical Society, NATO, International Union of Pure and Applied Biophysics (lUPAB), the World Federation of Scientists and the Italian National Research Council. One-third of the sixty participants were from Italy, but the majority came from eighteen other nations. Since the course was part of the International School of Biophysics, the biophysi cal point of view was emphasized in integrating the biology with the electrochemistry. Lecturers were asked to use a quantitative approach with accepted standards and proper units, since this is absolutely essential for developing an effective common language for communication across disciplines. Participants were also urged not to forget that biological systems could also be considered as physical systems. Ion channels are proteins and their properties as polyelectrolytes contribute to the specific biological properties. The existence of families of channels, with very similar structures but different selectivities, suggests that the specificities arise from slight variations of a general basic design. These perspectives on nerve-muscle function helped to make the school course a unique treatment of the subject.

Volumes I and 2 of this Plant Biotechnology series reviewed fundamental aspects of plant molecular biology and discussed production and analysis of the first generation of transgenic plants of potential use in agriculture and horticulture. These included plants resistant to insects, viruses and herbicides, which were produced by adding genes from other organisms. Realisation of the potential of plant breeding has led to a resurgence of interest in methods of altering the structure, composition and function of plant constituents, which represents an even greater challenge and offers scope for improving the quality of a wide range of agricultural products. This, in tum, has resulted in a re-evaluation of priorities and targets by industry. Volume 3 of this series considers the biochemical and gentic basis of the biosynthesis of plant products such as starch, lipids, carotenoids and cell walls, and evaluates the ways in which biosynthesis of these products can be modified for use in the food industries. Authors also cover the biosynthesis of rare secondary products and the function and application of proteins for plant protection and therapeutic use. The emphasis throughout is on the relationship between fundamen tal aspects of biosynthesis and structure-function relationships, and application of this knowledge to the redesigning and altering of plant products by molecular genetics."

From within complex structures of organisms and cells down to the molecular level, biological processes all involve movement. Muscular fibers slide on each other to activate the muscle, as polymerases do along nucleic acids for replicating and transcribing the genetic material. Cells move and organize themselves into organs by recognizing each other through macromolecular surface-specific interactions. These recognition processes involve the mu tual adaptation of structures that rely on their flexibility. All sorts of conformational changes occur in proteins involved in through-membrane signal transmission, showing another aspect of the flexibility of these macromolecules. The movement and flexibility are inscribed in the polymeric nature of essential biological macromolecules such as proteins and nucleic acids. For instance, the well-defined structures formed by the long protein chain are held together by weak noncovalent interac tions that design a complex potential well in which the protein floats, permanently fluctuating between several micro- or macroconformations in a wide range of frequencies and ampli tudes. The inherent mobility of biomolecular edifices may be crucial to the adaptation of their structures to particular functions. Progress in methods for investigating macromolecular structures and dynamics make this hypothesis not only attractive but more and more testable.

Research on thrombin structure and function has progressed significantly over the past three decades. We are continually discovering new functions f()r this enzyme in biology. Yet, until quite recently, a full, detailed, three dimensional picture of its structure was difficult to attain. We believe that this text represents a turning point and, more appropriately, a new start ing point for thrombin studies. Our goal for this text is to present a thorough and rounded-out coverage of thrombin chemistry and biochem istry in order to provide the biochemist and physiologist with an excellent desk reference on almost any thrombin-related problem. This volume is organized into three general thrombin topic areas: Structure, Biochemistry, and Physiology. In Part 1, Structure, we open with the complete three-dimensional x-ray structures of two inhibited human thrombin complexes, one of which is the thrombin-hirudin com plex. These complexes are also addressed in the chapter on structural studies in solution, which include NMR, ESR, and fluorescence. Part 2, Biochemistry, includes chapters on synthetic thrombin inhibitors, protein inhibitors (e.g., antithrombin III, hirudin), and thrombin interactions with factor XIII. Part 3, Physiology, covers such topics as chemotactic activities, interactions with cell surfaces, and the vascular endothelium.

Mesodenn is a key tissue in early development. It is involved in the differentiation of almost every organ in the body, not merely as a structural component, but as an active participant in the establishment of diverse cell types. All mesodenn is derived from ectoderm. Its appearance signals the start of a significant new phase in the development of the embryo. At this time all three genn layers are now present and myriad sequences of cell and tissue interactions begin to occur which will eventually give rise to the entire embryo. The control of the growth and differentiation of the mesoderm is critical for the production of a normal individual. Indeed, disturbance of the patterning of the mesoderm or of its interaction with other tissues plays a critical part in the fonnation of most congenital anomalies. The main focus of this book is therefore on the establishment, divergence and specialisation of mesodermal derivatives. The central role of the mesoderm in development has long been appreciated and a wide literature exists on its activity in certain specialised situations. Recently, however, an impetus to its study has been provided by new approaches opened up through biotechnological advances. Many of these advances are reflected in the reports in this volume. Scientists from various disciplines have become drawn to mesodermal tissues, and this volume may help them find a framework within which their work will fit.

In recent years rapid progress has been made in the areas of T cell and B cell biology, cell-cell and cell-matrix/stroma interactions. The use of isolated subunits of the T cell receptor invariant chains has been instrumental in defining their role in signal transduction and tyrosine phosphorylation. A role of src family phosphotyrosine kinases in T cell activation has been demonstrated and several phosphotyrosine kinase substrates have been identified and their functions characterized. Homologous recombinant techniques have led to the development of murine strains that lack CD4 or CD8 expression. These models are likely to be instrumental in studying the role of T cell subsets in autoimmune disorders, tissue transplant rejection and tumor rejection. A role of major histocompatibility complex I in the development of T cell subsets and NK cells has been defined. Recent data suggest a role of interaction between plasma membrane molecules of activated T helper cells and B cells, B cells primed with plasma membrane of activated T helper cells and cytokines, and interaction between bone marrow stromal cells and B cell progenitors and precursors, in the B cell development, proliferation, and differentiation. The structure and functions of adhesion molecules, especially with regard to signal transduction and homing events, are better defined.

Serpins (serine protease inhibitors) are a superfamily of proteins whose physiologi- cal action is primarily targeted to inhibiting serine proteases. There are instances where serpins are not inhibitors (and can carry steroid hormones for instance), yet key structural and functional elements found in all serpins are maintained in these 'non-inhibitor' ser- pins. Many serpins have well-described biological properties which influence pathophysi- ological events, including: antithrombin (historically called antithrombin III), ai-protease inhibitor (historically called ai-antitrypsin), and plasminogen activator inhibitor-I, just to mention a few. A deficiency or defect in antithrombin leads to venous thromboembolic disease, while a deficiency or defect in ai-protease inhibitor is associated with chronic obstructive pulmonary emphysema. In contrast, it has been suggested that increased levels of plasminogen activator inhibitor-l may be a predisposition to myocardial infarction. The list goes on for each of our own "favorite" serpin. The biological roles found for serpins are key participants in almost every physiological event. In other words, serine proteases are needed for many events in biology and the role of serpins to down regulate these pro- teases is essential. Thus, just using these three examples above for serpins and their patho- physiological roles reminds us that the medical costs to control such events is significant worldwide.

This monograph contains the proceedings from the Advanced Study Institute on "Vascular Endothelium: Physiological Basis of Clinical Problems" which took place in Corfu, Greece in June 1990. The meeting consisted of twenty-eight lectures, most of them adapted as full length papers in this volume, as well as numerous short oral and poster communications which are abstracted and also included in alphabetical order (pages 239-302). There were ninety-six participants from ten NATO and four other European countries. The meeting was the second in as many years dealing with a specific subject in Endothelial Cell biology. Following the 1988 discussion on "Receptors and Transduction Mechanisms", the present ASI recognized and tried to deal with the increasing overlap in interest between basic scientists studying endothelial cell functions and clinicians facing problems of known or suspected endothelial pathological involvement. As with any similar effort, we opted to be selective, rather than fail by trying to be inclusive, in the subjects covered. We chose to discuss diseases, such as atherosclerosis, sepsis, ARDS and stroke, based on their relevance to endothelial cell function and urgent need for new insights into their pathogenesis and treatment. Similarly, we examined endothelial cell functions by considering their relevance to disease and their potential for elucidating important pathologies. Obviously, some areas were covered superficially or not at all; this should not distract from their importance, but rather reflect on the constraints of time and -not at all negligibly -the bias of the organizing committee.

Proceedings of an international symposium, held in Ulm, Germany, September 21-24, 1994

This book deals with the cellular biology, biochemistry and physiology of photoreceptors and their interactions with the second-order neurons, bipolar and horizontal cells. The focus is upon the contributions made by these neurons to vision. Thus the basic neurobiology of the outer retina is related to the visual process, and visual defects that could arise from abnormalities in this part of the retina are highlighted in the first 16 chapters. Since all vertebrate retinas have the same basic structure and physiological plan, examples are given from a variety of species, with an emphasis upon mammals, extending to human vision. The last four chapters approach the problem from the other end. This part of the book covers a range of clinical conditions involving visual abnormalities that are due to cellular defects in the outer retina. Although the contents of this book do not represent the proceedings of a conference, the concept arose at an international symposium on 'Recent Advances in Retinal Research' which was held at the International Marine Centre in Oristano, Sardinia. We hope that the book will give a coherent, up to date review of the neurobiology and clinical aspects of the outer retina and encourage further integration of these areas. Retinal neurobiology has been an intense field of investigation for several decades. More recently, it has seen significant advances with the application of modern techniques of cell and molecular biology.

From the 19-29 May 1991 the NATO ASI Course PAsthma Treatment: A P Multidisciplinary Approach was held in Erice, on the rocky North West Coast of Sicily, facing the ancient Phoenician shore of the African Continent. Sixty NATO sponsored participants arriving from many different European Countries - Nato members and non - attended the course. Qualified researchers from Europe and the United States held extensive lectures, short meetings and small informal group discussions. Erice is a magical place which draws together people from different backgrounds and cultures under her Mediterrean charm, recreating the ancient Greek openair discussion atmosphere. And so, during the 10 days gathering, the extensive willingness of the senior investigators and the laudable enthusiasm of the younger participants was stimulated. All of the most recent findings in the biology and the pharmacology of Asthma were discussed, initially behind closed doors, to be unhurriedly continued along the alley ways of the "Cittadella della Scienza" , in Erice's small restaurants, and on her deserted beaches. The texts collected here are testimony to the high quality of the investigators contributions as well as their far reaching interests. I think that a Director of such a Course would be adequatly satisfied by merely considering the enthusiasm and high level involvement of every participant. He could not have been more satisfied after having considered the proceedings summerizing the scientific content of the meeting.

The origins of what have come to be known as the "Oxford" Conferences on modelling and the control of breathing can be traced back to a discussion between Dan Cunningham and Richard Hercynski at a conference dinner at the Polish Academy of Sciences in 1971. Each felt that they had benefited from the different perspectives from which the topic of ventilatory control was approached - predominantly physiological in the case of Dr Cunningham and predominantly mathematical in the case of Dr Hercynski. Their judgement at that time was that a conference on the control of breathing which allowed investigators with these different (but related) scientific perspectives to present and discuss their work, might prove fruitful. We would judge that this has amply been borne out, based upon the success of the series of conferences which resulted from that seminal dinner conversation. The first conference, entitled "Modelling of a Biological Control System: The Regulation of Breathing" was held in Oxford, UK, in 1978. Subsequent conferences were: "Modelling and the Control of Breathing" at Lake Arrowhead, California, in 1982; "Con cepts and Formulations in the Control of Breathing" in Solignac, France, in 1985; "Respi ratory Control: A Modeling Perspective" at Grand Lakes, Colorado, in 1988; and "Control of Breathing and Its Modelling Persepctive" at the Fuji Institute in Japan in 1991. The conferences, subsequent to the one in Oxford, have all resulted in well-received published proceedings.

The cardiac system represents one of the most exciting challenges to human ingenuity. Critical to our survival, it consists of a tantalizing array of interacting phenomena, from ionic transport, membrane channels and receptors through cellular metabolism, energy production to fiber mechanics, microcirculation, electrical activation to the global, clinically observed, function, which is measured by pressure, volume, coronary flow, heart rate, shape changes and responds to imposed loads and pharmaceutical challenges. It is a complex interdisciplinary system requiring the joint efforts of the life sciences, the exact sciences, engineering and technology to understand and control the pathologies involved. The Henry Goldberg Workshops were set up to address these multivariable, multidisciplinary challenges. Briefly, our goals are: To encourage international cooperation and foster interdisciplinary interaction between scientists from the different areas of cardiology; to relate microscale cellular phenomena to the global, clinically manifested cardiac function; to relate conceptual modeling and quantitative analysis to experimental and clinical data; to gain an integrated view of the various interacting parameters, identify missing links, catalyze new questions, and lead to better understanding of the cardiac system. The outstanding success of past workshops has encouraged their continuation. The first Henry Goldberg Workshop, held in Haifa in 1984, introduced the concept of interaction between mechanics, electrical activation, perfusion and metabolism, emphasizing imaging in the clinical environment. The second Workshop, in 1985, discussed the same parameters with a slant towards the control aspects.

This is the third meeting we have organized which has explored the meaning of fetal neural developmental disruption in the etiology of schiwphrenia. The first was sponsored by the Schiwphrenia Research Branch with the scientific cooperation of Dr. David Shore. We met in Washington; the output of the meeting was published in a book entitled, Fetal Neural Development and Adult Schizophrenia. Cambridge University Press. 1991. The next meeting was an Advanced Research Workshop sponsored by NATO and was held at n Ciocco. Castelvecchio Pascoli. This meeting was reported in a NATO volume. Developmental Neuropathology of Schizophrenia and was edited by Mednick. Cannon. Barr and La Fosse. The current meeting has noted several advances in the field. There are additional psychiatric illnesses which have been found to be related to maternal viral infection in the second trimester. There have been studies reported which have definitely observed a viral infection in the mothers of fetuses who later evidenced schirophrenia. More evidence has been published which has replicated the "second-trimester effect." In the future studies will be wise to provide serological evidence of a viral infection and information on the precise viruses involved. Another important step will be to determine whether second-trimester maternal viral infection is related to a behavioral deficit in the infant. If neural development has been compromised. it might be possible to detect deficits in the infant with the proper measures. We look forward to future meetings at which these new areas might be explored.

From recent developments in the rapidly growing area of neuroscience it has become increasingly clear that a simplistic description of brain function as a broad collection of simple input-output relations is quite inadequate. Introspection already tells us that our motor behavior is guided by a complex interplay between many inputs from the outside world and from our internal "milieu," internal models of ourselves and the outside world, memory content, directed attention, volition, and so forth. Also, our motor activity normally involves more than a circumscribed group of muscles, even if we intend to move only one effector organ. For example, a reaching movement or a reorientation of a sensory organ almost invariably requires a pattern of preparatory or assisting activities in other parts of the body, like the ones that maintain the body's equilibrium. The present volume is a summary of the papers presented at the symposium "Sensory Interaction in Posture and Movement Control" that was held at Smolenice Castle near Bratislava, Slovakia, as a Satellite Symposium to the ENA Meeting 1994 in Vienna. The focus of this meeting was not only restricted to the "classical" sensory interactions such as between vestibular and visual signals, or between otolith and semicircular canal inputs. Rather, the symposium tried to consider also the interplay between perception and action, between reflexive and volitional motor acts as well as between sensory driven or self-initi ated motor acts and reafferent inputs."

Among the fishes, a remarkably wide range of biological adaptations to diverse habitats has evolved. As well as living in the conventional habitats of lakes, ponds, rivers, rock pools and the open sea, fish have solved the problems of life in deserts, in the deep sea, in the cold antarctic, and in warm waters of high alkalinity or of low oxygen. Along with these adaptations, we find the most impressive specializations of morphology, physiology and behaviour. For example we can marvel at the high-speed swimming of the marlins, sailfish and warm-blooded tunas, air-breathing in catfish and lung fish, parental care in the mouth-brooding cichlids and viviparity in many sharks and toothcarps. Moreover, fish are of considerable importance to the survival of the human species in the form of nutritious, delicious and diverse food. Rational exploitation and management of our global stocks of fishes must rely upon a detailed and precise insight of their biology. The Chapman & Hall Fish and Fisheries Series aims to present timely volumes reviewing important aspects of fish biology. Most volumes will be of interest to research workers in biology, zoology, ecology and physiology but an additional aim is for the books to be accessible to a wide spectrum of non-specialist readers ranging from undergraduates and postgraduates to those with an intrerest in industrial and commercial aspects of fish and fisheries."

The Handbook of Behavioral Neurobiology series deals with the aspects of neurosciences that have the most direct and immediate bearing on behavior. It presents the most current research available in the specific areas of sensory modalities. This volume explores circadian rhythms.

Aquaculture is now recognized as a viable and profitable enterprise worldwide. As aquaculture technology has evolved, the push toward higher yields and faster growth has involved the enhancement or replacement of natural foods with prepared diets. In many aquaculture operations today, feed accounts for more than one-half the variable operating cost. Therefore, knowledge of nutrition and practical feeding of fish is essential to successful aquaculture. This book is not written exclusively for scientists but also for students, practicing nutritionists, and aquaculturists. It covers the known nutrient requirements and deficiency effects for different fishes, and digestion and metabolism of nutrients and energy. It discusses nutrient sources and preparation of practical and research feeds. It gives directions for conducting fish nutrition and feeding experiments. Feeding practices for salmonids, channel catfish, tilapias, shrimps and hybrid striped bass are presented. Since the first edition of this book was printed, the National Research Council of the National Academy of Sciences has revised the nutrient requirements for fish. These revisions are in the present edition. Other additions to this revised edition are chapters on nutrition and fish health, and bioavailability of nutrients. Each original chapter has been meticulously revised and updated with new information. Aquaculture is a dynamic area and new technologies are being introduced continuously; therefore, some of the material discussed in this revised edition may become obsolete quickly. Nonetheless, the material presented has been thoughtfully selected and updated to make it of maximum use to persons whose interests range from general aquaculture to animal nutrition to feed manufacture.

A presentation of the most elementary form of pulsatile flow as an important prerequisite for the study of other flow applications in biological systems. The book provides in a single source a complete treatment of the fluid dynamics of flow with the required mathematics and emphasis on the basis mechanics. The style and level of this book make it accessible to students and researchers in biophysics, biology, medicine, bioengineering and applied mathematics working in theoretical and clinical work on the cardiovascular system, as well as in the design of new instrumentation, medical imaging systems, and artificial organs. With problems and exercises.

Two techniques were used to estimate the L/M cone ratio, best-fit linear sum of the L- and M-cone spectral sensitivities to heterochromatic flicker photometric spectral sensitivity and psychometric function shape for point source detection of lights of varying wavelength. Data from five color-normal observers run on both paradigms all are consistent with a preponderance of L-cones relative to M-cones though there are individual differences in the estimates of L/M cone ratio. The observers showed congruence in their individual results across technique. In a separate study, the perceptual consequences of individual variation in L/M cone populations were evaluated by looking for a relation between flicker photometric spectral sensitivity and the spectral locus of equilibrium yellow. No significant relation was found, suggesting that receptor populations do not play a major role in the normalization of the perceptual red/green opponent channel. ACKNOWLEDGEMENT Supported in part by USPH NEI grant EY00901. REFERENCES Adam, A. (1969) Foveal red-green ra. C10S c:,f normals, colorblinds and heterozygotes. Proceedings Tel-Hasrcomer Hospital (Tel-Aviv). 8: 2-6. Ahnelt, P. , H. Kolb and R. Pflug. (1987). Identification of a subtype of cone photoreceptor, likely to be blue sensitive, in the human retina. Journal of Compa:cative Neurology. 255: 18-34. Alpern, M. and E. Pugh. (1977). variation in the action spectrum of erythrolabe among deuteranopes. Journal of Physiology (London). 266: 613-646. Boynton, R. (1979). Human Color Vision. New York, Holt, Rinehart and Winston. Brindley, G. (1954) The summation areas of human colour-receptive mechanisms at increment threshold.

The International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis was held in Academia Sinica, Taipei, Taiwan, Republic of China, on August 30 - September 1, 1989. This Symposium has provided a forum for the free exchange of information in this important and rapidly advancing research field. This proceedings volume provides a published record of 46 papers presented at the Symposium. The sponsors have exerted no influence on the scientific opinions or positions of the participants in the Symposium. It is hoped that this Symposium will stimulate further worldwide cooperation and collaboration in these vital fields for the benefit of all human kind. This volume is composed of four parts. The first part consists of 8 papers on Fibrinogen and Fibrin: Biochemistry, Molecular Biology, and Physiology. The second part contains 16 papers on Coagulation and Fibrinolysis: Biochemistry, Molecular Biology, and Physiology. The third part has 10 papers on Cardiovascular Cell Biology: Biochemistry, Molecular Biology, and Physiology. The fourth part comprises 12 papers on Clinical Studies of the Cardiovascular System: Thrombotic and Bleeding Disorders and Thrombolytic Therapy. The Author Index with addresses of all contributors and the Subject Index of all 46 papers are arranged at the end of this volume.