Книги автора: Derek J. Chadwick

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.

Using a multidisciplinary approach, it combines anatomical, cellular and physiological studies by preeminent experts. Features important insights into the function of the hypothalamus.

T cells are a specialized population of immune cells that aid the immune system in combating various types of invading pathogens. This book presents up-to-the-minute data on the role of T cells in autoimmune diseases.

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.

Drawing together contributions from a diverse group of international experts in the field, this collection of papers examines the biology and pathology of elastin at the molecular level. Topics include the structure, ultrastructure and function of elastin; elastin regulation; elastin's role in aging, lung development and disease and atherosclerosis; as well as related aspects of pharmacology and nutrition.

Insect-Plant Interactions and Induced Plant Defence Chair: John A. Pickett, 1999 This book examines the sophisticated mechanisms that plants use to defend themselves against attack by insects and pathogens, focusing on the networks of plant signalling pathways that underlie these defences. In response to herbivory, plants release a complex blend of as many as 100 volatile chemicals, known as semiochemicals ('sign chemicals'). These act as an airborne SOS signal, revealing the presence of the herbivore to the predators and parasitoids that are its natural enemies. Plants also have endogenous defence mechanisms that can be induced in response to pathogens, and separate chapters deal with systemic acquired resistance, phytoalexins, and the interacting pathways in pathogen and pest resistance. The book discusses underlying biochemical mechanisms by which plant stress leads to the biosynthesis of chemical signals from pools of secondary metabolite precursors, or even from the primary metabolism source. Finally, consideration is given to the possibilities for exploiting these signalling pathways by plant molecular genetics. The use of plant signals and their analogues to switch on defence pathways in crop plants is covered in depth. Bringing together contributions from entomologists, chemical ecologists, molecular biologists and plant physiologists this book is truly interdisciplinary, and will be essential reading for anyone with an interest in agricultural pest control.

ATP, the intracellular energy source, is also an extremely important cell–cell signalling molecule for a wide variety of cells across evolutionarily diverse organisms. The extracellular biochemistry of ATP and its derivatives is complex, and the multiple membrane receptors that it activates are linked to many intracellular signalling systems. Purinergic signalling affects a diverse range of cellular phenomena, including ion channel function, cytoskeletal dynamics, gene expression, secretion, cell proliferation, differentiation and cell death. Recently, this class of signalling molecules and receptors has been found to mediate communication between neurons and non-neuronal cells (glia) in the central and peripheral nervous systems. Glia are critical for normal brain function, development and response to injury. Neural impulse activity is detected by glia and purinergic signalling is emerging as a major means of integrating functional activity between neurons, glia and vascular cells in the nervous system. These interactions mediate effects of neural activity on the development of the nervous system and in association with injury, neurodegeneration, myelination and cancer. Bringing together contributions from experts in diverse fields, including glial biologists, neurobiologists and specialists in purinergic receptor structure and pharmacology, this book considers how extracellular ATP acts to integrate communication between different types of glia, and between neurons and glia. Beginning with an overview of glia and purinergic signalling, it contains detailed coverage of purine release, receptors and reagents, purinergic signalling in the neural control of glial development, glial involvement in information processing, and discussion of the interactions between neurons and microglia.

Gramicidin channels have been studied intensively for more than 25 years. They serve as model transport systems for large protein ion channels, since it is difficult to glean high-resolution structural information on the latter. This book includes contributions from virtually all the major scientists studying gramicidin channels and is the only compilation of work in this field. It discusses crystallographic, spectroscopic, electrophysiological and computational studies, especially in the light of the recent availability of high-resolution structural data, and it compares these with insights derived from larger systems. As well as drawing together much new and exciting work in this field, it provides pointers to promising new research directions.

Recent application of the techniques of molecular biology and patch-clamp physiology has led to rapid advances in understanding the molecular events in chemosensory transduction. In this book, the latest results are presented and discussed by leading scientists. The extensive coverage encompasses many important topics, including mucous domains; microchemical heterogeneity in the mucociliary complex of the olfactory epithelium; membrane currents and mechanisms of olfactory transduction, and genetic and pathological taste variation.

Details the application of positron emission tomography (PET) to the mapping of human cerebral cortical function. Coverage includes all aspects of PET technology. Includes chapters on somatosensory, motor and visual systems, and higher-order processes such as attention, memory, learning, intention and language. The clinical usefulness of PET is discussed in relation to psychiatric illness and to functional recovery after brain injury.

The field of neural transplantation is at a crucial stage, with important clinical trials on transplantation in patients with Parkinson's disease nearing completion and novel, alternative approaches to fetal transplantation being developed. This timely book brings together leading neuroscientists, clinicians, and cell and developmental biologists to discuss the use of neural transplants in neurodegenerative disorders, such as Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, multiple sclerosis and spinal cord injury. There is also extensive coverage of the potential alternatives to freshly derived fetal tissue as the source of transplants, for example xenografts, encapsulated cells and immortalized stem cells. With authoritative contributions and lively discussion sections, this book presents much new and exciting work in this field and identifies promising new research directions.

Smooth muscle contraction is a vital component of the functioning of blood vessels, the uterus, airways and the bladder. Its malfunction can lead to serious pathological conditions, such as hypertension and pre-term labour. The calcium ion plays a central role in smooth muscle function, increasing in concentration for contraction and decreasing for relaxation. Calcium entry into the cell is facilitated by the sarcoplasmic reticulum (SR). This book explores the latest research on the role of the sarcoplasmic reticulum (SR) in smooth muscle function. It examines the control and modulation of the SR and how this may vary among smooth muscle types. Potential therapeutic implications are also discussed. Discusses new and exciting work in this area and identifies promising new research directions. Considers the advances in this relatively unexplored field, offering new insights into the role of the SR muscle. Brings together contributions from key workers, both in basic and clinical science, whose studies range from physiological to pathological and molecular to whole animal.

The increase in the world population and changes in welfare have led to an enormously expanding demand for food. In the industrialized world, food surpluses rather than shortages are a problem together with adverse environmental impacts from the overuse of chemicals and excessive exploitation of agricultural land. In the developing world, food production cannot keep up with population growth and the gap between demand and supply is growing. This book explores the theme of sustainable agricultural development in the developing world, with a particular focus on crop protection. Includes chapters on the ecology of food production, on sustainable agriculture and crop protection methods, on the economics of food production and more.

Microbial responses to acidic and alkaline pH are important in many areas of bacteriology. For example, the mechanisms of resistance to acidic pH are important in the understanding of the passage of human pathogens through the acid of the stomach; and an understanding of microbial degradation of alkaline industrial waste is important for the environment. Bringing together contributions from an international and interdisciplinary group of experts working on the many aspects of bacterial cellular responses to pH, this stimulating volume draws together new and innovative work in this area. It delineates both similarities and differences between mechanisms of tolerance and response, providing readers with an invaluable resource on the subject.

Contains the presentations and discussions that took place during a symposium at the CIBA Foundation on October 1-3, 1990 on the subject of catalytic antibodies. The recognition that monoclonal antibodies can possess catalytic activity is a recent advance with profound ramifications for chemistry. In addition to their potential commercial applications as catalysts for reactions, for which there are no known enzymes, antibodies promise to provide valuable insight into the detailed mechanisms of biological catalysis and organic chemistry.

Epigenetics pertains to the development of an organism from an undifferential cell, resulting in the successive formation and development of organs and parts that did not pre-exist in the fertilized egg. An exciting and stimulating volume which used the extensive knowledge of basic transcriptional control as a foundation to explore the more complex and interesting level at which genes can be regulated.

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.

Prestigious contributors describe the genetic, molecular, anatomical and neurochemical mechanisms and pathways that operate to regulate and control circadian rhythmicity and functioning in organisms ranging from unicellular algae to human beings. Also considers the implications of the basic and clinical research for humans.