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This book provides a comprehensive overview of the development of the human central nervous system (CNS) in the context of its many developmental disorders due to genetic, environmental and hypoxic/ischaemic causes. The book contains three general, introductory chapters in which an overview of the development of the human brain and spinal cord, a summary of mechanisms of development as obtained in experimental studies in various invertebrates and vertebrates, and an overview of the causes of congenital malformations are presented. The developmental disorders of the human brain and spinal cord are presented in a regional, more or less segmental way, starting with neurulation and neural tube defects, and ending with developmental disorders of the cerebral cortex. These chapters are abundantly illustrated in colour with carefully chosen clinical case studies with imaging data, and when available, postmortem verification of the developmental disorders involved.In thethird edition, more emphasis has been given to the developmental ontology based on the prosomeric approach, and fetal development. Prenatal diagnosis by ultrasound, MRI and DTI, and classifications of developmental disorders have been updated. A number of new Clinical Cases have been included. Several new co-authors participate in various chapters. The book is intended for advanced medical students, and all those clinicians working with children and adults with developmental disorders of the CNS. Unique to the book is the integration of data from human embryology, experimental and molecular findings in mice in particular, imaging and developmental neuropathology.

This textbook describes in detail the process of cancer metastasis from a single cell in the primary site through its arduous journey to the sentinel lymph node as the main gateway and beyond to distant sites. The most up-to-date knowledge on key topics in the molecular biology, diagnosis, and treatment of metastatic cancer is highlighted by a large panel of experts. The book begins with a comprehensive overview of the genetic and molecular mechanisms that promote or inhibit cancer metastasis through lymphatic pathways to lymph nodes or through vascular pathways to distant sites, providing the reader with an essential basic knowledge. This is followed by further details on the role of the immune system within the primary tumor and the lymph node and the importance of the microenvironment at the metastatic site. The role of the sentinel lymph node in cancer metastasis is emphasized. Special attention is also given to state-of-the-art imaging techniques for the detection of early-stage cancer and cancer metastases, as well as the use of liquid biopsies in sarcoma, prostate, gastrointestinal, and lung cancer. Clinical patterns of malignant tumors arising in different organ systems are compared, described, and discussed with the goal of determining what similarities and/or differences exist. The book concludes with a detailed discussion of surgical intervention, radiation, and systemic therapy of primary and metastatic cancer, and briefly previews several emerging topics, such as the latest findings on personalized cancer therapy, cancer stem cells, unique molecular mechanisms of virus-induced cancer, the impact of the microbiome on cancer metastasis and the application of artificial intelligence in cancer metastasis research. By providing fundamental knowledge of the biological and clinical aspects of cancer metastasis, this book will be an important reference for cancer researchers, clinical oncologists, teachers, and students. Written by experts in the field, each chapter includes a summary of the chapter's key points and open-ended questions that address pressing issues in the field and encourage the reader to consider future directions.

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

These four volumes with close to one thousand contributions are the proceedings from the VIIIth International Congress on Photosynthesis, which was held in Stockholm, Sweden, on August 6- 11, 1989. The site for the Congress was the campus of the University of Stockholm. This in itself was an experiment, since the campus never before had been used for a conference of that size. On the whole, it was a very sucessful experiment. The outcome of a congress depends on many contributing factors, one major such factor being the scientific vigour of the participants, and I think it is safe to say that the pariticipants were vigourous indeed. Many exciting new fmdings were presented and thoroughly dicussed, indoors in the discussion sessions as well as outdoors on the lawns. For the local organizing committee it was very rewarding to participate in these activities, and to watch some of our younger colleagues for the first time being subjected to the impact of a large international congress. The stimulating effect of this event on the local research atmosphere has been substantial. As was the case with the proceedings from both the 1983 and 1986 Congresses these proceedings have been compiled from camera ready manuscripts, and the editing has mainly consisted of finding the proper place for each contribution and distributing the manuscripts into four volumes with some int~rnal logic in each. In this I have had the invaluable help from Dr.

Scientific reviews are now of two complementary types: short, very up-to-date articles, as are found in the Trends series, and the more traditional longer re­ views, which are more comprehensive but take longer to publish. The Subcellu­ lar Biochemistry series belongs to the latter category where a number of reviews on a broad topic are collected together in the one volume. It has been the aim of this volume to summarize the present state of knowledge of membrane assembly. It is appreciated that some relevant topics have not been included, and an editor's selection is restricted by the many calls on potential authors who are unable to meet all requests made to them. The absence of a discussion of the roles of lipids is,'however, a reflection of the fact that a recent volume in this series, edited by Dr. H. 1. Hilderson, has been devoted to this subject (Vol. 16, Intracellular Transfer of Lipid Molecules), and readers are recommended to this source.

Abraham Rosenberg assembles the groundbreaking work of preeminent international scientists to provide the most current, state-of-the-art presentation of research in siabiology. This concise volume examines the historical development of the field and reviews current knowledge on the genetic, immunologic, oncologic, neurodevelopmental, pathogenic, and cell regulatory properties of sialic acid. Outstanding features of this work include exhaustive reference material and detailed information tables.

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.

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.

Comparative endocrinology helps to find the roots of homeostatic regulation in organisms. In this context, many years ago a series of experiments were done, which demonstrated the hormonal regula­ tion also on the invertebrate level. The mechanisms are partly similar, partly different, from those found in vertebrates. The new receptor era of mammalian endocrinology stimulated research on invertebrate hormone receptors, and sophisticated methods are applied also to determine hormones. The experiments demonstrated the existence and even similar function of these structures and signaling molecules. However, data on hormones and receptors at the lowest level of metazoan life and the highest level of protozoan life were not at our disposal. About two decades ago, first observations on the presence of hormone receptors reacting to vertebrate hormones in protozoa were made. Since the early 1980s we know that hormone-like molecules similar to those of higher vertebrates are present also in unicellular organisms. The presence of some second messengers in Tetrahymena was recognized. Since then, the research has been extended and many structures - previously believed to be solely vertebrate characteristics, such as opiate receptors, similar to mammalian ones - were found in unicellular organisms. These observations justified the assumption of a complete endocrine system at protozoan level, where - considering the unicellularit- this seemed to be not required. However, it became clear that the roots of endocrine communication date back at least 2 billion years.

“Photosynthesis: Plastid Biology, Energy Conversion and Carbon Assimilation” was conceived as a comprehensive treatment touching on most of the processes important for photosynthesis. Most of the chapters provide a broad coverage that, it is hoped, will be accessible to advanced undergraduates, graduate students, and researchers looking to broaden their knowledge of photosynthesis. For biologists, biochemists, and biophysicists, this volume will provide quick background understanding for the breadth of issues in photosynthesis that are important in research and instructional settings. This volume will be of interest to advanced undergraduates in plant biology, and plant biochemistry and to graduate students and instructors wanting a single reference volume on the latest understanding of the critical components of photosynthesis.

In the past few years there has been the increased recognition that the effects of oxidative stress are not limited to the damage of cellular constituents. There is now evidence that reactive oxygen species (ROS) can alter cell function by acting upon the intermediates, or second messengers, in signal transductions. Such effects on signaling mechanisms probably account for the role of oxidative stress in inflammation, aging, and cancer. This volume brings together internationally recognized researchers in both the major areas covered by the book, oxidative stress and signal transduction. The work is organized in three sections. The first deals with the immediate cellular responses to oxidative stress and the production of second messengers. The second details the connection between second messengers and the gene. The third part looks more closely at the level of the gene.

In this book, the authors review the effects of uPAR on the actin, intermediate filaments and microtubules that constitute the cell cytoskeleton, and the mechanisms used by uPAR to modulate intracellular signalling and temporally fine tune cytoskeletal dynamics. The effects of cytoskeletal components of uPAR expression and cellular distribution are examined as well. In addition, Duchenne Muscular Dystrophy (DMD) is an inherited disorder characterized by progressive muscular degeneration and cognitive impairment due to mutations in the DMD gene. Elucidation of the molecular basis for this illness has determined that cytoskeleton and the product of the DMD gene called dystrophin work in a coordinated way to maintain fibre muscle integrity. The authors describe the scientific path that allows elucidation of the molecular basis of DMD. Furthermore, cell motility is central to many aspects of cell, tissue, and organ function in both health and disease. Some of the more popular published experimental approaches to study cell motility are discussed. Also examined are the IQGAP family of proteins, which are now known to act at the interface between cellular signalling pathways and the actin cytoskeleton.

This reference is a volume in the Handbook of Physiology, co-published with The American Physiological Society. Growth in knowledge about the microcirculation has been explosive with the field becoming fragmented into numerous subdisciplines and subspecialties. This volume pulls all of the critical information into one volume. - Meticulously edited and reviewed. Benefit: Provides investigators a unique tool to explore the significance of their findings in the context of other aspects of the microcirculation. In this way, the updated edition has a direct role in helping to develop new pathways of research and scholarship - Highlights the explosive growth in knowledge about the microcirculation including the biology of nitric oxide synthase (NOS), endothelial cell signaling, angiogenesis, cell adhesion molecules, lymphocyte trafficking, ion channels and receptors, and propagated vasomotor responses. Benefit: Microcirculatory biology has become fragmented into numerous sub-disciplines and subspecialties, and these reference reintegrates the information in one volume

The lipids of cellular membranes not only serve roles in controlling the structure and fluidity of the membrane, but are increasingly recognized for their roles as signalling molecules and modifiers of membrane protein function. Recent studies described in this volume reveal striking changes in membrane lipids during aging and in age-related diseases such as cancer, cardiovascular disease and neurodegenerative disorders. Lipids including inositol phospholipids, cholesterol, sphingolipids and ceramides play important roles in signalling cellular responses to stress and specific stimuli such as growth factors, cytokines and neurotransmitters. One or more of these lipid mediators has been linked to the pathogenesis of age-related diseases. This book provides a comprehensive review of specific membrane lipid mediators and their roles in aging and age-related disease.

Proceedings of the 16th ESACT Meeting, April 25-29, 1999, Lugano, Switzerland

The daily production of hundreds of billions of blood cells through the process of hematopoiesis is a remarkable feat of human physiology. Transport of oxygen to tissues, blood clotting, antibody- and cellular-mediated immunity, bone remodeling, and a host of other functions in the body are dependent on a properly functioning hematopoietic system. As a consequence, many pathological conditions are attributable to blood cell abnormalities, and a fair number of these are now clinically treatable as a direct result of hematopoietic research. Proliferation of hematopoietic stem cells, and their differentiation into the many different lineages of functional mature cells, is highly regulated and responsive to many environmental and physiological challenges. Our relatively advanced understanding of this stem cell system provides potentially important insights into the regulation of development in other tissues, many of which are now being acknowledged as stem ce- based, perhaps even into adulthood. The recent public and scientific fanfare following announcement of human embryonic stem cell studies suggests that stem cell research will continue to be a relevant and exciting topic.

The progress in photosynthesis research has been transduction and expression of photosynthetic genes quite dramatic during the last two decades. The which occur both in the nuclear/cytosol compartment Nobel prizes awarded to Peter Mitchel (1978), to and in the chloroplast. Several chapters are devoted Johannes Deisenhofer, Hartmut Michel and Robert to the transcription machinery and the two plastid Huber (1988), to Rudolf Marcus (1992) and to Paul RNA-polymerase complexes, to the regulation of Boyer and John Walker (1997) have recognized— photosynthesis genes by redox signaling both in directly or indirectly—the structural or mechanistic chloroplasts and in the prokaryotic systems, as well discoveries related to the photosynthetic energy as to the sugar sensing mechanisms. Chapters also conversion. Actually, photosynthesis may be the first cover important regulatory aspects imposed by po- biological process described, not only in molecular transcriptional modifications and degradation of terms, but even in atomic terms. mRNA molecules, and the translational regulation Much of the excitement around photosynthesis is mechanisms operating in chloroplasts. based upon the connection between light and life. Part III—Biogenesis, turnover and senescence— is closely connected to the question of regulation. Light is an elusive ‘substrate'that cannot be handled The chapters included emphasize how the c- in the same way as conventional chemical substrates plicated membrane structures, composed of both in biological metabolic reactions.

Structure and function of the components of the photosynthetic apparatus and the molecular biology of these components have become the dominant themes in advances in our understanding of the light reactions of oxygenic photosynthesis. Oxygenic Photosynthesis: The Light Reactions presents our current understanding of these reactions in thylakoid membranes. Topics covered include the photosystems, the cytochrome b6-f complex, plastocyanin, ferredoxin, FNR, light-harvesting complexes, and the coupling factor. Chapters are also devoted to the structure of thylakoid membranes, their lipid composition, and their biogenesis. Updates on the crystal structures of cytochrome f, ATP synthase and photosystem I are presented and a section on molecular biology and evolution of the photosynthetic apparatus is also included. The chapters in this book provide a comprehensive overview of photosynthetic reactions in eukaryotic thylakoids. The book is intended for a wide audience, including graduate students and researchers active in this field, as well as those individuals who have interests in plant biochemistry and molecular biology or plant physiology.