Книги автора: Jamie A. Goode

Brings together key new results of interdisciplinary collaborations among various research fields on rhodopsin including the photoreceptive mechanism of rhodopsins, the molecular mechanism of the visual transduction process, visual processes in the retina and other transduction processes in the retina and brain. The structures of the rhodopsin molecule are studied in the fields of protein chemistry, molecular biology, organic chemistry and structural biology; the ultra fast reactions of the retinal protein are studied in physics, biophysics, physical chemistry, organic chemistry and photobiology; the phototransduction in retinal proteins and visual cells are studied in biophysics, biochemistry, biophysical chemistry and photobiology; and the localization in the tissues is studied in anatomy and histochemistry. The diversity of visual systems in various animals is studied in zoology and comparative biochemistry.

Sensory Guidance of Movement Chairman: Mitchell Glickstein, 1998 In the past few years there has been an increasing recognition of the multiplicity of sensory and motor areas of the cerebral cortex. However, still relatively little is known about the way in which sensory areas are functionally linked to motor areas. On the basis of current anatomical evidence, there are three major pathways involved in this linking. One of these routes is by way of cortico-cortical links, beginning in the primary sensory areas of the cortex, and connecting via a series of synaptic relays to motor or premotor areas. There are also two massive subcortical routes. One of these involves the basal ganglia, the other the cerebellum. This book focuses on current research on the structure and functions of these three pathways and their role in the sensory guidance of movement. Motor psychophysicists have made progress in characterizing the nature of movements such as reaching and grasping, and how such movements are modified by incoming sensory information. Anatomical studies have revealed important new information about the ways in which sensory information is relayed to the basal ganglia and cerebellum. There is now a volume of scanning evidence about the activity of brain areas in humans and recordings from individual neurons in animals during sensory guided movement. This book summarizes much of this recent knowledge and provides a forum for suggesting new avenues for further study. The topics covered also have important implications for understanding the role of these pathways in human disease.

Amyloid fibrils are associated with a range of pathological disorders including Alzheimer's Disease, Down's syndrome, diabetes, cardiomyopathies, and transmissible spongiform encephalopathies. This volume is a comprehensive account of recent developments in the understanding of the process of amyloid fibrils. Contains up-to-date data on all of the clinical problems which, despite their pathological significance, are still largely unsolved.

An invaluable book containing a series of interdisciplinary discussions between clinical and basic scientists. Biology of IGF-1: Its interaction with insulin and health and malignant states focuses on key issues such as: the definition of danger zones the development of methods for early recognition of malignant states linked to IGF-1 and/or insulin possible approaches to preventative intervention the relevance in this field of research to the development of novel therapeutic approaches to treating certain cancers.

Foremost neurophysiologists and psychophysicists provide pertinent information on the nature of representation at the earliest stages as this will constrain the disposition of all subsequent processing. This processing is discussed in several different types of visual perception.

Environmental statistics is a rapidly growing discipline that is important not only as a division of professional and academic statistics, but also in the accumulation of data on environmental effects and in the formulation of environmental policy by government agencies. This book features contributions from policy makers, scientists actively involved in collection of data, and professional, academic and government statisticians. These explore the interfaces between the different areas of application of environmental statistics and consider the future applications of methods arising from this discipline. Some of the chapters deal specifically with environmental models and methods. Here, the contributors explain specialized statistical techniques that have been developed for analysing environmental data and mathematical models that have been applied to the problem of integrating large amounts of environmental data into a coherent picture of particular environmental systems. Several of the contributions deal specifically with the problems involved in co-ordinating data collection over large geographical areas and over many dimensions of measurement. Finally, the book discusses the problems of formulating specific environmental policies given the nature of the information that has been made available using environmental statistical methods.

This book explores existing and potential strategies for using the genome sequences of human, mouse, other vertebrates and human pathogens to solve key problems in the treatment of immunological diseases and chronic infections. The assembled genome sequences now provide important opportunities for solving these problems, but a major bottleneck is the identification of key sequences and circuits controlling the relevant immune reactions. This will require innovative, interdisciplinary and collaborative strategies of a scale and complexity we are only now beginning to comprehend. Specific problems addressed include the following: What kinds of information are we lacking to understand how the genome sequence specifies the differentiation and response of immune system cells, and system behaviour such as immunological memory and tolerance? Which genome sequences and cellular circuits cause or prevent pathological immune responses to foreign pathogens, allergens or self-tissues? Which host and pathogen genome sequences and cellular circuits explain the failure of sterilizing immune responses to sophisticated human pathogens such as the agents of tuberculosis, malaria, metazoan parasites and chronic viruses? Containing contributions from a range of leading experts in the field, this book provides an important new perspective for clinical immunologists and basic researchers alike.

The potential lipotoxic effect of accumulation of fatty acids in non-adipose tissues is thought to be a major component in the development of insulin resistance. Chronic exposure to high concentrations of free fatty acids in the blood affects pancreatic β cell function, insulin secretion and lipid synthesis in the liver, and storage in adipose tissue. Maintaining the normal levels of fatty acids requires coordinated regulation between the liver, adipose tissue and skeletal muscle. This book deals with the molecular aspects of fatty acid action in obesity and insulin resistance. The topics include lipid metabolism and adipose tissue biology, and β cell function and insulin resistance. Chapters deal with the molecular genetics and molecular physiology of energy homeostasis.

Degeneration of sensory receptors or of the nerves innervating them leads to a sensory deficit. Various strategies have been tried for promoting regrowth of sensory receptors, particularly in the eye and ear. The latest data from experimental studies in animals are presented in the book including applications of BDNF and CNTF in the eye and epidermal growth factor in the ear.

The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups. The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues. The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation. While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues. With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.

This book brings together contributions from key investigators in the area of pathological pain. It covers the molecular basis of receptors and channels involved in nociception, the possible messages that cause neuropathic plasticity, spinal plasticity in neuropathy, plastic changes in opioid systems in neuropathy and opioid tolerance, and plastic changes related to pathological pain.

With the recent renaissance in mitochondrial biology and increasing recognition of their role in many diseases, this book provides a timely summary of the current state-of-the-art in mitochondrial research. The book opens with the regulation of mitochondrial replication and biogenesis and reviews the mechanisms and functional consequences of mitochondrial fission and fusion. Further chapters address mitochondria and oxidative stress and their roles in cell signalling and cell death. The book includes extensive, fascinating discussion of the biochemistry of mitochondrial cell signalling (especially involving calcium) and of oxidative stress. The nature of the proteins engaged in these processes, many only recently discovered, is covered in detail. Mitochondria have been strongly implicated in neurodegenerative diseases such as Parkinson’s, Huntington’s and amyotrophic lateral sclerosis. They are also affected in cancer, ageing and cardiovascular disease. The final section of the book reviews mitochondrial mutations and their consequences in ageing and other phenotypic manifestations. The authors discuss how mitochondrial proteins might constitute important therapeutic targets and describe initial attempts to develop compounds that can regulate their function.

Osteoarthritis is a chronic degenerative disease associated with joint pain and loss of joint function. It has an estimated incidence of 4 out of every 100 people and significantly reduces the quality of life in affected individuals. The major symptoms are chronic pain, swelling and stiffness; severe, chronic joint pain is often the central factor that causes patients to seek medical attention. Within the affected joint, there is focal degradation and remodelling of articular cartilage, new bone formation (osteophytes) and mild synovitis. Several mechanisms are thought to contribute to osteoarthritic joint pain. These include mild synovial inflammation, bone oedema, ligament stretching, osteophyte formation and cartilage-derived mediators. Changes in joint biomechanics and muscle strength also influence the severity and duration of joint pain in osteoarthritis. Within the nervous system, the relative contributions of peripheral afferent nociceptive fibres and central mechanisms remain to be defined, and there is limited information on the phenotype of sensory neurons in the OA joint. Importantly, there is no relation between clinical severity, as measured by radiographic changes, and the presence and severity of joint pain. Patients with severe joint pain may have normal joint architecture as determined by X-ray, whereas patients with considerable evidence of joint remodelling may not have significant joint pain. Treatments for osteoarthritic joint pain include non-steroidal anti-inflammatory compounds, exercise, corrective shoes and surgical intervention. There remains a critical need for improved control of joint pain in osteoarthritis. This book brings together contributions from key investigators in the area of osteoarthritic joint pain. It covers the clinical presentation of joint pain, the pathways involved in joint pain, osteoarthritis disease processes and pain, experimental models and pain control. The discussions provide insights into the nature of osteoarthritic joint pain, identify key studies needed to advance understanding of the problem, highlight possible intervention points and indicate future pathways towards a better treatment of osteoarthritic joint pain.

A number of chronic respiratory diseases including chronic bronchitis, asthma, cystic fibrosis and bronchiectasis are characterized by mucus hypersecretion. Following damage to the airway epithelium, a repair process of dedifferentiation, regenerative proliferation and redifferentiation takes place that is invariably accompanied by mucus hypersecretion as a key element in the host defence mechanism. In chronic respiratory diseases, however, excessive mucus production leads to a pathological state with increased risk of infection, hospitalization and morbidity. An understanding of the mechanisms that underlie and maintain this hypersecretory phenotype is therefore crucial for the development of rational approaches to therapy. Despite a high and increasing prevalence and cost to healthcare services and society, mucus hypersecretion in chronic respiratory disease has received little attention until recently, probably because of the difficulties inherent in studying this pathology. Only in the last few years have some of the genes involved in mucus secretion been characterized. The recent availability of genomic sequence information and specific antibodies has led to an explosion of interest in this area making this publication particularly timely. This book draws together contributions from an international and interdisciplinary group of experts, whose work is focused on both basic and clinical aspects of the problem. Coverage includes epidemiology, airways infection and mucus hypersecretion, the genetics and regulation of mucus production, models of mucus hypersecretion, and the implications of new knowledge for the development of novel therapies.

The heat shock, or cell stress, response was first identified in the polytene chromosomes of Drosophila. This was later related to the appearance of novel proteins within stressed cells, and the key signal stimulating this appearance was identified as the presence of unfolded proteins within the cell. It is now known that this is a key mechanism enabling cells to survive a multitude of physical, chemical and biological stresses. Since the promulgation of the ‘molecular chaperone’ concept as a general cellular function to control the process of correct protein folding, a large number of molecular chaperones and protein folding catalysts have been identified, and it has been recognized that not all molecular chaperones are stress proteins and vice versa. The discovery of molecular chaperones as folding proteins went hand-in-hand with their recognition as potent immunogens in microbial infection. It was subsequently shown that administration of molecular chaperones such as Hsp60, Hsp70 or Hsp90 could inhibit experimental autoimmune diseases and cancer. More recently evidence has accumulated to show that certain molecular chaperones are also present on the surface of cells or in extracellular fluids. A new paradigm is emerging: at least some molecular chaperones are secreted proteins with pro- or anti-inflammatory actions, regulating the immune response in human diseases such as coronary heart disease, diabetes and rheumatoid arthritis. In addition to having direct effects on cells, molecular chaperones can bind peptides and present them to T cells to modulate immune responses. This may be significant in the treatment of cancer. This is the first book bringing leading researchers in this field together to review and discuss: our current knowledge of cell stress response and molecular chaperones the changing paradigms of protein trafficking and function cell stress proteins as immunomodulators and pro- and anti-inflammatory signalling molecules the role of these proteins in various chronic diseases and their potential as preventative or therapeutic agents. The Biology of Extracellular Molecular Chaperones is of particular interest to immunologists, cell and molecular biologists, microbiologists and virologists, as well as clinical researchers working in cardiology, diabetes, rheumatoid arthritis and other inflammatory diseases.

Cl- absorption and HCO3- secretion are intimately associated processes vital to epithelial function, itself a key physiological activity. Until recently the transporters responsible remained obscure, but a breakthrough occurred with the discovery of the SLC26 transporters family. It is now clear that the SLC26 transporters have broad physiological functions since mutations in several members are linked to a variety of diseases. This book describes the properties of this family in detail, with contributions from the leading global researchers in the field. Complementary views from experts on other ion channels are offered in the discussions, which make fascinating reading. This family consists of at least 10 genes, each of which has several splice variants. Most members of the family are expressed in the luminal membrane of epithelial cells. Characterization of anion transport by three members has revealed that all function as Cl-/HCO3- exchangers, suggesting that SLC26 transporters are responsible for the luminal Cl-/HCO3- exchange activity. The SLC26 transporters are activated by the CF transmembrane conductance regulator and activate it in turn, leading to a model in which these molecules act together to mediate epithelial Cl- absorption and HCO3- secretion. The book includes chapters on the transport of other molecules by the SLC26 family, including oxalate in the kidney and sugars in cochlear hair cells amongst others. It also describes recent discoveries that most SLC26 transporters bind to scaffold proteins and that they all contain a conserved domain predicted to participate in protein-protein interactions. These suggest the SLC26 transporters exist in complexes with other Cl- and HCO3- transporters, and possibly other regulatory proteins. This book explores the functional role of these interactions, leading to better understanding of transepithelial fluid and electrolyte secretion and the diseases associated with it.

This exciting book brings together an international and interdisciplinary group of experts to discuss the importance of pulsatile signalling in the induction of biological responses. Coverage includes the basic mechanisms involved in hormone pulsatility, the significance of pulsatility in normal and disease conditions, the relevance of circadian rhythms, changes with ageing, and detailed consideration of specific peptide hormone systems. This book includes contributions from professionals working in both basic and clinical research and reveals much new and exciting work in this area and promises new research directions.

This book draws together contributions from basic, pharmaceutical and clinical sciences aimed at a better understanding of the structure and function of hERG and the molecular basis for compound binding. It features regulatory authority perspectives on preferred preclinical test systems and includes topics on hERG channel gating, regulation of functional expression, pharmacological properties of hERG/IKr channels, drug-induced long QT syndrome and preclinical evaluation and regulatory recommendations for assessing QT prolongation risks. Better understanding of the role of the hERG channel in drug-induced cardiac arrhythmias should ultimately lead to the development of important, new and safer medicines.

Rice is the most important food crop for half the world's population. Over the last three decades, the imporvement in human nutrition and health in Asia has largely been attributable to a relatively stable and affordable rice supply. The challenge to produce enough rice for the future, however, remains daunting, as the current rate of population growth outpaces that of increases in rice production. Science has a central role to play in raising rice productivity and this book highlights areas of plant science that are particularly relevant to solving the major constraints on rice production. Examining molecular, genetic and cellular techniques, it considers recent advances in four research approaches for increasing yields and improving the nutritional quality of rice. Plant genomics: knowing the identity and location of each gene in the rice genome is of immense value in all aspects of rice science and cultivar improvement. Molecular biological approaches to increase yield: to produce more biomass by increasing photosynthetic rate and duration, and by improving grain filling. Enhancing tolerance to biotic and abiotic stresses: with new DNA array technologies, it is now possible to assess global genomic response to stresses. Understanding the relationships among stress pathways may create new opportunities for gene manipulation to enhance tolerance to multiple biotic and abiotic stresses. Improving nutritional quality in the grain: knowledge of the biosynthesis of micronutrients in plants permits genetic engineering of metabolic pathways to enhance the availability of micronutrients.

Chronic inflammation predisposes to some forms of cancer and the host response to malignant disease shows several parallels with inflammation and wound healing. The cells involved in inflammation are detected in a range of common cancers, together with the inflammatory cytokines and members of the chemokine ligand/receptor systems. Neutralization or deletion of the gene for some inflammatory cytokines confers resistance to tumour induction and experimental metastasis. Over-expression of such cytokines in tumour cells may enhance malignant potential. Certain chemokines are likely to subvert antitumour immunity by favouring development of ineffective Type 2 responses. Tumour cells may even utilize chemokine receptors in homing to lymph nodes and other organs. Thus, the cells, cytokines and chemokines found in tumours are more likely to contribute to tumour growth, progression and immunosuppression than they are to mount an effective host antitumour response. This book draws together contributions from an international group of scientists and clinicians from diverse disciplines, ranging from epidemiology to immunology, cell biology, molecular oncology, molecular medicine and pharmacology to debate these and related issues. Topics covered include the epidemiological links between cancer and inflammation, the parallels between inflammation and cancer, the role of inflammation in cancer, inflammatory genes as risk factors for cancer initiation and progression, inflammation and cancer angiogenesis, and preventative and therapeutic strategies. Related Novartis Foundation symposia: 252 Generation and Effector Functions of Regulatory Lymphocytes Chair: Jean-François Bach 254 Immunoinformatics: Bioinformatic Strategies for Better Understanding of Immune Function Chair: Hans-Georg Rammensee