This volume describes the current state of our knowledge on the neurobiology of muscle fatigue, with consideration also given to selected integrative cardiorespiratory mechanisms. Our charge to the authors of the various chapters was twofold: to provide a systematic review of the topic that could serve as a balanced reference text for practicing health-care professionals, teaching faculty, and pre-and postdoctoral trainees in the biomedi cal sciences; and to stimulate further experimental and theoretical work on neurobiology. Key issues are addressed in nine interrelated areas: fatigue of single muscle fibers, fatigue at the neuromuscular junction, fatigue of single motor units, metabolic fatigue studied with nuclear magnetic resonance, fatigue of the segmental motor system, fatigue involving suprasegmental mechanisms, the task dependency of fatigue mechanisms, integrative (largely cardiorespiratory) systems issues, and fatigue of adapted systems (due to aging, under-and overuse, and pathophysiology). The product is a volume that provides compre of processes that operate from the forebrain to the contractile proteins.

The symposium on "Zinc in Soils and Plants" is the third in a series which began with "Copper in Soils and Plants" in Perth in 1981 and continued with "Manganese in Soils and Plants" in Adelaide in 1988. The symP9sium brings together a series of valuable accounts of many aspects of the reactions of zinc in soils, the uptake, transport and utilization of zinc in plants, the diagnosis and correction of zinc deficiency in plants and the role of zinc in animal and human nutrition. I am grateful for the financial support provided by Grains Research and Development Corporation, Rural Industries Research and Development Corporation, Wool Research and Development Corporation, Ansett Australia, and Qantas Australian. I am most appreciative of the willingness of many scientists to act as referees: G S P Ritchie, R J Gilkes, N C Uren, K Tiller, BLeach, H Greenway, N E Longnecker, J F Loneragan, Z Rengel, C A Atkins, J W Gartrell, P J Randall, D G Edwards, R J Hannam, R J Moir, J E Dreosti, N Suttle, C L White, H Marschner, N Wilhelm, M McBride. All provided valuable comments on the manuscripts. Finally, I thank Mrs M Davison who provided excellent secretarial assistance. A.D. Robson September 1993 Chapter 1.

This book describes in general how the chemosensory systems of fish function at various levels. In many ways, fish are typical vertebrates differing only slightly from other vertebrates including humans. In other ways, their aquatic environment imposes strict requirements or offers unique opportunities which have resulted in some unusual functions having no counterpart in higher vertebrates. This new volume is necessitated by advances in many vital areas as the field of chemical senses continues to grow at a rapid pace. Most significant is the application of the contemporary electrophysiological technique of patch-clamping, recognition of a second messenger system in chemosensory transduction processes and the identification of hormonal pheromones in fish reproductive behaviour. The last major synthesis of our knowledge about fish chemoreception, Chemoreception in Fishes, was published ten years ago (Elsevier, Amsterdam, 1982). In that volume four aspects of fish chemoreception, Le. morphology of the peripheral chemoreceptors. primary sensory processes, roles in behaviour, and its interactions with environment, were discussed. This book is intended to be helpful to students, scientists and aquacul turists not only as a source book but also as a textbook on chemical senses."

Methods in Bone Biology is unique in being devoted to describing the methodology used by bone researchers. This book describes in detail the techniques of cell and organ culture used in the study of bone and bone cell function and the techniques used to monitor the skeleton and skeletal remodelling both in clinical and experimental settings.

Charles E. Hess Department of Environmental Horticulture University of California Davis, CA 95616 Research in the biology of adventitious root formation has a special place in science. It provides an excellent forum in which to pursue fundamental research on the regulation of plant growth and development. At the same time the results of the research have been quickly applied by commercial plant propagators, agronomists, foresters and horticulturists (see the chapter by Kovar and Kuchenbuch, by Ritchie, and by Davies and coworkers in this volume). In an era when there is great interest in speeding technology transfer, the experiences gained in research in adventitious root formation may provide useful examples for other areas of science. Interaction between the fundamental and the applied have been and continue to be facilitated by the establishment, in 1951, of the Plant Propagators' Society, which has evolved into the International Plant Propagators' Society, with active programs in six regions around the world. It is a unique organization which brings together researchers in universities, botanical gardens and arboreta, and commercial plant propagators. In this synergistic environment new knowledge is rapidly transferred and new ideas for fundamental research evolve from the presentations and discussions by experienced plant propagators. In the past 50 years, based on research related to the biology of adventitious root formation, advances in plant propagation have been made on two major fronts.

Electric currents and electromagnetic fields have been applied to biological systems, particularly humans, with both therapeutic and pathological results. This text discusses biological responses to electric currents and electromagnetic fields, including medical applications and shock hazards. It covers fundamental physical and engineering principles of responses to short-term electrical exposure and emphasises human reactions, although animal responses are considered as well, and the treatment covers reactions from the just-detectable to the clearly detrimental. An important new chapter discusses standards for human exposure to electromagnetic fields and electric current and demonstrates how these standards have been developed using the principles treated in earlier chapters.

Photobiology - the science of light and life - begins with basic principles and the physics of light and continues with general photobiological research methods, such as generation of light, measurement of light, and action spectroscopy. In an interdisciplinary way, it then treats how organisms tune their pigments and structures to the wavelength components of light, and how light is registered by organisms. Then follow various examples of photobiological phenomena: the design of the compound eye in relation to the properties of light, phototoxicity, photobiology of the human skin and of vitamin D, photomorphogenesis, photoperiodism, the setting of the biological clock by light, and bioluminescence. A final chapter is devoted to teaching experiments and demonstrations in photobiology.
This book encompasses topics from a diverse array of traditional disciplines: physics, biochemistry, medicine, zoology, botany, microbiology, etc., and makes different aspects of photobiology accessible to experts in all these areas as well as to the novice. It is intended primarily for graduate students and for researchers who wish to look outside their speciality, but can also act as a source of information for undergraduate students.

This book will give an overview of insect ovaries, showing the diversities and the common traits in egg growth processes. The idea to write this book developed while looking at the flood of information which appeared in the early 1980s on early pattern formation in Drosophila embryos. At this time a significant breakthrough was made in studies of this little fly, combining molecular biological methods with classical and molecular genetics. The answers to questions about early pattern formation raised new questions about the architecture of ovaries and the growth of eggs within these ovaries. However, by concentrating only on Drosophila it is not possible to form an adequate picture of what is going on in insect ovaries, since the enormous diversity found among insects is not considered sufficiently. Almost forgotten, but the first to study the architecture of ovaries, was Alexander Brandt writing in 1878 in aber das Ei und seine Bildungsstaette (On the egg and its organ of development). More than 100 years later, a series of ten books or more would be required to survey all the serious informa tion we have today on insect oogenesis. Thus, this book is a personal selection and personal view on the theme, and the authors must be excused by all those scientists whose papers could not be included. The book briefly describes the ectodemes, i. e."

This book is dedicated to the memory of two colleagues and friends, Amico Big- nami and Hendrick Vander Los. They were both pioneers in their fields: Bignami on on- togenesis and function of neuroglia, and Van der Los on brain plasticity and neuronal circuitry. Their ideas are further pursued by the authors in this book. Some of the chapters are products of a conference dedicated to these two scientists entitled "Recent Advances in Neurobiology: Plasticity and Regeneration." The conference was organized by the Insti- tute of Developmental Neuroscience and Aging and sponsored by the Region della Valle d' Aosta. Also, several chapters are written by colleagues who knew well either Amico or Hendrick and were invited to contribute to this dedication. The book is divided in four sections. The first part covers neurons, neuroglia includ- ing microglia, their plasticity and phenotypic expression, and specific functions and inter- actions. It is now established that neuroglia are an intimate component of the neuronal environment and thought to regulate several neuronal functions. More recently microglia have become prominent as the immune cells in the CNS. This part contributes new infor- mation for these cellular interactions. The second part deals with neuronal and glial cell plasticity as it relates to regeneration and neurodegeneration, more or less an extension of Part I. In recent years the role of transplantation in regeneration has become promising.

Reproduction is the origination of new organisms from pre-existing ones. Among more than 35 separated forms of reproduction including several types of gamogony, parthenogenesis, agamogenesis, fission and division, and plas motomy, the bisexual mode of reproduction via fertilization provides genetic variability that allows species to adapt quickly to competitive and constantly changing environments. Several excellent reviews and books have been written in the past to analyse the mechanisms of fertilization in different eukaryotic species. During the last few years, however, renewed attention has been paid to examining the process of oocyte fertilization at the cellular/molecular level not only within a single species/group but also through different phylogenetic lineages. As a result of this effort, knowledge of the molecular pathways used by oocytes and spermatozoa at fertilization has increased, but still many ques tions remain to be answered. Being aware of the necessity of providing an inte grated view of the process of fertilization, this book has been entirely devoted to reviewing the process of oocyte fertilization at the cellular/molecular level in two different and separated groups of eukaryotic organisms: protozoa and metazoan animals. The book is organized into six sections dealing with oocyte fertilization in protozoa, invertebrates, teleost fishes, amphibians, birds and mammals. These sections are followed by a summary/concluding chapter that provides a com parative overview of the process of fertilization in these groups of eukaryotes."

Providing a survey on current research in eukaryotic signal transduction, some of the topics covered are, the biochemistry and biophysics of cell surface receptors, G-protein mediated signalling pathways, regulation of cyclic AMP, Ca2+, inositol phosphate pathways, the structure and regulation of receptors which are tyrosine protein kinases, and cellular responses to integrated signals.

Though it is a pleasure to write a short foreword to this collection of excellent scientific papers covering a range of biological topics, the rather depressing feature is the small number of papers. All-electronic publishing is developing and your Editors do have great faith in it. One problem for potential authors has been the reluctance of the abstracting journals to pay any attention to electronic journals - perhaps Springer should make a rapid move in this area and start the first all-electronic journal abstracting this type of literature. However, even the paper citation journals are starting to pay attention to the medium. The particular advantages of all-electronic publishing are beginning to emerge more clearly and it is clear that publishing video material is a unique advantage of our format. Several papers took advantage of this - for example those by Riehle and others on cell behaviour in tunnels, by Bereiter-Hahn and Voss on zonation in the plasmalemma and by Pavlikova, Zicha, Chaloupkova and Vesely on cell motility of tumour cells. These papers made essential and extensive use of video material, publishing some material of great originality. The work on cell pola rity and calcium ions in Fucus embryos by Brownlee, Manison and Anning used animation to present their results in an especially clear way. The facility of use of animation is another special advantage of our type of publication that should be more widely used."

G.P. Stamou describes the adaptive strategies that allow arthropods to cope with the severity of Mediterranean environments. After an introduction to the structure and function of Mediterranean-type ecosystems, ecophysiological adaptations to water stress and varying temperature are considered. Further, activity patterns and life cycle tactics are discussed in relation to the peculiarity of Mediterranean environments. Phenological patterns and population dynamics as well as community structures are also presented. The volume ends with a synthesis of life history tactics.

The fifth Oxford Conference was held on September 17th-19th, 1991, at the Fuji Institute of Training in Japan -the first time that the meeting has taken place in the Asian area. The facts that only a relatively few Japanese had attended previous Oxford Conferences and that Japan is far from other regions with possible participants made the organizers anticipate a small attendance at the meeting. However, contrary to our expectations, 198 active members (72 foreign and 126 domestic participants) submitted 146 papers from 15 countries. This was far beyond our preliminary estimate and could have caused problems in providing accommodation for the participants and in programming their scientific presentations. These difficulties, however, were successfully overcome by using nearby hotels, by telecasting presentations into a second lecture room and by displaying a substantial number of poster presentations during the whole period of the meeting. The meeting had two types of sessions: regular and current topics. The first paper in each session represented a shon overview or introduction so as to make it easier for the audience to comprehend the problems at issue. Because of the large number of papers submitted, carefully selected speakers (mostly well-known scholars) made excellent presentations that were followed by lively discussions. In this way, the conference laid a foundation on which to base its continued scientific success.

This book presents a review of the existing literature on natural mycotoxins to create a comprehensive reference for mycotoxin levels. Each entry includes contamination, concentration rate, mostly mean mycotoxin concentration of organs (human and animal) and country of origin of the sample. Due to the serious spoilage and health issues the presence of mycotoxins can cause, it is imperative that corresponding scientists, health institutions and the food and feed industries have a more qualified understanding of mycotoxins in living things. To this end, Natural Mycotoxin Contamination in Humans and Animals provides an excellent resource. The present book complements the series of the author's previous books, Mycotoxins in Feedstuffs and Mycotoxins in Foodstuffs, in that it is a review of the literature to create a comprehensive reference for mycotoxin levels. As with Mycotoxins and their Metabolites in Humans and Animals, the focus remains the same, but the scope now covers natural mycotoxins only. Comprehensive reference of natural mycotoxin levels in humans and animals Easy-to-use database of mycotoxins Each entry is comprehensive

The Henry Goldberg Workshops were set up to address the following goals: (1) To foster interdisciplinary interaction between scientists and cardiologists, identify missing links, and catalyze new ideas. (2) To relate basic microscale phenomena to the global, clinically manifested cardiac function. (3) To relate conceptual modeling and quantitative analysis to experimental and clinical data. (4) To encourage international cooperation so as to disperse medical and technological knowhow and lead to better understanding of the cardiac system. The first Henry Goldberg Workshop, held in Haifa in 1984, introduced the concept of interaction between cardiac 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. The third Goldberg Workshop, held in the USA at Rutgers University in 1986, highlighted the transformation of the microscale activation phenomena to macroscale activity and performance, relating electrophysiology, energy metabolism, and cardiac mechanics. The fourth Goldberg Workshop, in 1987, continued the effort to elucidate the interactions among the various parameters affecting cardiac performance, with emphasis on the ischemic heart. The fifth Workshop, held in Cambridge, UK, in 1988, dwelt on the effects of inhomogeneity of the cardiac muscle on its performance in health and disease. The sixth Workshop highlighted the role of new modem imaging techniques, that allow us to gain more insight into local and global cardiac performance in cardiac research and clinical practice.

The International Societyon Oxygen Transport to Tissue (ISOTT) was founded in 1973 "to facilitate the exchange of scientific information among those interested in any aspect of the transport and/or utilization of oxygen in tissues." Its members span virtually all disciplines, extending from various branches of clinical medicine such as anesthesiology, ophthalmology and surgery through the basic medical sciences of physiology and biochemistry to most branches ofthe physical sciences and engineering. The eighteenth annual meeting of ISOTT was held in 1990 for four days, from July 19 to 22, in the Sheraton Hotel in Townsville, Queensland, Australia. The usual ISOTT format, which was originated in 1985 by Dr. Ian Longmuir, was continued. Almost all presentations were posters with an accompanying, scheduled, brief, slide presentation and discussion. All posters remained in place for the entire four days of the meeting. There were no simultaneous sessions. Essentially all aspects of physiological transport were covered at this meeting with possibly somewhat more emphasis on methods and instrumentation. The editors gratefully acknowledge the photographic skills of Dr. Jens Hoper who took the group picture during the outing to Magnetic Island on July 21. We are also most grateful to Dr. Rod D. Braun of Evanston for his invaluable editorial assistance. This volume is the thirteenth in the Plenum series Oxygen Transport to Tissue.

During the past decade interest in the formation of complex disorderly patterns far from equilibrium has grown rapidly. This interest has been stim ulated by the development of new approaches (based primarily on fractal geometry) to the quantitative description of complex structures, increased understanding of non-linear phenomena and the introduction of a variety of models (such as the diffusion-limited aggregation model) that provide paradigms for non-equilibrium growth phenomena. Advances in computer technology have played a crucial role in both the experimental and theoret ical aspects of this enterprise. Substantial progress has been made towards the development of comprehensive understanding of non-equilibrium growth phenomena but most of our current understanding is based on simple com puter models. Pattern formation processes are important in almost all areas of science and technology, and, clearly, pattern growth pervades biology. Very often remarkably similar patterns are found in quite diverse systems. In some case (dielectric breakdown, electrodeposition, fluid-fluid displacement in porous media, dissolution patterns and random dendritic growth for example) the underlying causes of this similarity is quite well understood. In other cases (vascular trees, nerve cells and river networks for example) we do not yet know if a fundamental relationship exists between the mechanisms leading the formation of these structures.

Ecology is characterized by a rapidly growing complexity and diversity of facts, aspects, examples, and observations. What is badly needed is the development of common patterns, of rules that, as in other sciences such as physics, can more generally explain the increasing complexity and variability we observe. Tom White, being one of the "seniors" in ecology, makes such an attempt in his book. the pattern he shows and explains with numerous examples from the entire animal kingdom is a universal hunger for nitrogen, a misery that drives the ecology of all organisms. He advocates that the awareness of this fundamental role that the limitation of nitrogen plays in the ecology of all organisms should be as a much part of each ecologis's intellectual equipment as is the awareness of the fact of evolution by means of natural selection. His claim is that not "enery" but "nitrogen" is the most limited "currency" in the animal world for the production and growth of their young.

Similarities in structure and function between pigs and human beings include size, feeding patterns, digestive physiology, dietary habits, kidney structure and function, pulmo nary vascular bed structure, coronary artery distribution, propensity to obesity, respiratory rates, tidal volumes and social behaviors. Since the pig is an omnivore, it provides an adaptable model to evaluate chronic and acute exposures to xenobiotics such as alcohoL caffeine, tobacco, food additives and environmental pollutants. Swine have been used successfully as models to evaluate alcoholism, diabetes, absorption, digestion, total paren teral nutrition, organ transplantation, atherosclerosis, exercise, hypertension. hemorrhagic hypotension, melanoma, gingivitis, obstructive and reflux nephropathy. osteochondrosis. dermal healing and septic shock. A severe and worsening shortage of organs and tissues for transplantation in patients with severe organ failure has encouraged the consideration of inter species or xenotransplan tation. In developing programs toward this end, the pig generally is viewed as the preferred donor because of its size, physiology and availability. The pig harbors relatively few diseases which could be transmitted inadvertently to human patients. The ability to genetically modify swine to ameliorate the consequences of the human immune response offers a further significant advantage. Another important consideration for an animal model is that basic biologic back ground information be available for investigators to design future prospective studies."

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

Introduction to Mammalian Reproduction is a welcome contribution to the fields of gametogenesis, gamete transport, fertilization, and reproduction technologies. Key topics covered include:
*formation and maturation of male gametes;
*morphology and physiology of female gametes;
*how the sperm meets the egg;
*sperm-egg fusion, egg activation, and implantation of fertilized egg;
*assisted reproduction and environmental chemicals that have an effect on formation and function of male and female gametes. This book is for both researchers and students involved in reproductive biology.

Discovery of the mechanism for V(D)J hypermutation remains a basic goal of immunology despite the best efforts of many labo ratories. The existence of catalyzed, site-specific mutation and its exploitation for the somatic evolution of lymphocytes are re markable adaptations, yet since the discovery of hypermutation in 1970 (see cover), much hard work has generated little. Indeed, our knowledge of what is probably absolutely required for the mutator's action can be succinctly expressed: /g gene enhancers. Table 1 of Winter et a .'s chapter puts into a historical perspec tive how our notions of the mutator have changed over the years. Despite these modest gains, most of us feel that this is the best of times. Our work has not only shown us what the mutator is not, it has also, like an artist's preliminary sketch, defined the questions and experiments we must face without diminishing the potential for new biology. In short, it is great fun to toil against a significant and enigmatic problem."

The field of olfactory research and chemical communication is in the early stages of revolutionary change, and many aspects of this revolution are reflected in the chapters in this book. Thus, it should serve admirably as an up-to-date reference. First, a wide range of vertebrate groups and species are represented. Second, there are excellent reviews of specific topics and theoretical approaches to communication by odors, including chapters on signal specialization and evolution in mammals, the evolution of hormonal pheromones in fish, alarm pheromones in fish, chemical repellents, the chemical signals involved in endocrine responses in mice, and the controversy over human pheromones. Third, there are exciting new findings presented in numerous specific topic areas, such as the chemis try of pheromones in a wide range of species (salamanders to elephants), the chemistry of proteins that control the release of pheromones, the molecular biology and physiology of detection, coding and response to odor signals, the effects of experience on sensitivity to odors, the role of genes of the immune system in odor production and in human mate choice, the function and perception of scent over-marks, the recognition of individuals and kin by odors, the influence of odors on predator-prey interactions, and the use of odors to help control pests. This book is an offshoot of the Eighth International Symposium on Chemical Sig nals in Vertebrates, held at Cornell University in Ithaca, New York, July 20-25, 1997, hosted and organized by Bob Johnston.

It has been great fun to write this book, even though it has taken longer than planned, and occasionally been exasperating. The most difficult problem was deciding what to exclude among so many interesting things, because the available material usually exceeded the space. Because a book like this covers so many aspects, each component must be limited. This book is intended for graduate and undergraduate students as well as professional scientists who want to work with animal flight or to gain some insight into flight mechanics, aerodynamics, energetics, physiology, morpho logy, ecology and evolution. My aim has not been to give the whole mathe matical explanation of flight, but to provide an outline and summary of the main theories for the understanding of how aerofoils respond to an airflow. I also hope to give the reader some insight into how flight morphology and the various wing shapes have evolved and are adapted to different ecological niches and habitats."