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The student of biolo,gical science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably concerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook of biology. This outline then sets out to provide by building on this basis, the conceptual framework within which modern research work is progressing and aims to give the reader an indication of the problems, both conceptual and practical, which must be overcome if progress is to be maintained.
This book describes the evolution of ideas relating to the mechanism of muscular contraction since the discovery of sliding filaments in 1954. An amazing variety of experimental techniques have been employed to investigate the mechanism of muscular contraction and relaxation. Some background of these various techniques is presented in order to gain a fuller appreciation of their strengths and weaknesses. Controversies in the muscle field are discussed along with some missed opportunities and false trails. The pathway to ATP and the high energy phosphate bond will be discussed, as well as the discovery of myosin, contraction coupling and the emergence of cell and molecular biology in the muscle field. Numerous figures from original papers are also included for readers to see the data that led to important conclusions. This book is published on behalf of the American Physiological Society by Springer. Access to APS books published with Springer is free to APS members.
Understanding the molecular mechanism of muscle contraction started with the discovery that striated muscle is composed of interdigitating filaments which slide against each other. Sliding filaments and the working-stroke mechanism provide the framework for individual myosin motors to act in parallel, generating tension and loaded shortening with an efficient use of chemical energy. Our knowledge of this exquisitely structured molecular machine has exploded in the last four decades, thanks to a bewildering array of techniques for studying intact muscle, muscle fibres, myofibrils and single myosin molecules. After reviewing the mechanical and biochemical background, this monograph shows how old and new experimental discoveries can be modelled, interpreted and incorporated into a coherent mathematical theory of contractility at the molecular level. The theory is applied to steady-state and transient phenomena in muscle fibres, wing-beat oscillations in insect flight muscle, motility assays and single-molecule experiments with optical trapping. Such a synthesis addresses major issues, most notably whether a single myosin motor is driven by a working stroke or a ratchet mechanism, how the working stroke is coupled to phosphate release, and whether one cycle of attachment is driven by the hydrolysis of one molecule of ATP. Ways in which the theory can be extended are explored in appendices. A separate theory is required for the cooperative regulation of muscle by calcium via tropomyosin and troponin on actin filaments. The book reviews the evolution of models for actin-based regulation, culminating in a model motivated by cryo-EM studies where tropomyosin protomers are linked to form a continuous flexible chain. It also explores muscle behaviour as a function of calcium level, including emergent phenomena such as spontaneous oscillatory contractions and direct myosin regulation by its regulatory light chains. Contraction models can be extended to all levels of calcium-activation by embedding them in a cooperative theory of thin-filament regulation, and a method for achieving this grand synthesis is proposed. Dr. David Aitchison Smith is a theoretical physicist with thirty years of research experience in modelling muscle contractility, in collaboration with experimental groups in different laboratories.
The extremely potent substance botulinum neurotoxin (BoNT) has attracted much interest in diverse fields. Originally identified as cause for the rare but deadly disease botulism, military and terrorist intended to misuse this sophisticated molecule as biological weapon. This caused its classification as select agent category A by the Centers for Diseases Control and Prevention and the listing in the Biological and Toxin Weapons Convention. Later, the civilian use of BoNT as long acting peripheral muscle relaxant has turned this molecule into an indispensable pharmaceutical world wide with annual revenues >$1.5 billion. Also basic scientists value the botulinum neurotoxin as molecular tool for dissecting mechanisms of exocytosis. This book will cover the most recent molecular details of botulinum neurotoxin, its mechanism of action as well as its detection and application.
This book explores the author’s wide-ranging work on muscle research, which spans more than 50 years. It delves into the dogmas of muscle contraction: how the models were constructed and what was overlooked during the process, including their resulting shortcomings. The text stimulates general readers’ and researchers’ interest, highlights the author’s pioneering work on the electron microscopic recording of myosin head power and recovery strokes, and presents a frank discussion on how the original work sometimes tends to be overlooked by competing scientists, who hinder the progress of science.
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How is the heartbeat generated? What controls the strength of contraction of heart muscle? What are the links between cardiac structure and function? How does our understanding of skeletal and smooth muscle and non-muscle cells influence our thinking about force development in the heart? Are there important species differences in how contraction is regulated in the heart? How do the new molecular data fit together in understanding the heart beat? What goes wrong in ischemia, hypertrophy, and heart failure? This book paints a modern `portrait' of how the heart works and in this picture the author shows a close-up of the structural, biochemical, and physiological links between excitation and contraction. The author takes the reader through a series of important, interrelated topics with great clarity and continuity and also includes many useful illustrations and tables. The book starts by considering the cellular structures involved in excitation-contraction coupling and then described the characteristics of the myofilaments as the end effector of excitation-contraction coupling. A general scheme of calcium regulation is described and the possible sources and sinks of calcium are discussed in simple, but quantitative terms. The cardiac action potential and its many underlying currents are reviewed. Then the characteristics of some key calcium transport systems (calcium channels, sodium/calcium exchange and SR calcium uptake and release) are discussed in detail. This is then built into a more integrated picture of calcium regulation in succeeding chapters by detailed discussions of excitation-calcium coupling mechanisms (in skeletal, cardiac, and smooth muscle), the interplay between calcium regulatory processes, and finally mechanisms of cardiac inotropy, calcium overload, and dysfunction (e.g., ischemia, hypertrophy, and heart failure). Excitation-Contraction Coupling and Cardiac Contractile Force – Second Edition is an invaluable source of information for anyone who is interested in how the heart beat is controlled and especially suited for students of the cardiovascular system at all levels from medical/graduate students through senior investigators in related fields.
Defines the current status of research in the genetics, anatomy, and development of the nematode C. elegans, providing a detailed molecular explanation of how development is regulated and how the nervous system specifies varied aspects of behavior. Contains sections on the genome, development, neural networks and behavior, and life history and evolution. Appendices offer genetic nomenclature, a list of laboratory strain and allele designations, skeleton genetic maps, a list of characterized genes, a table of neurotransmitter assignments for specific neurons, and information on codon usage. Includes bandw photos. For researchers in worm studies, as well as the wider community of researchers in cell and molecular biology. Annotation copyrighted by Book News, Inc., Portland, OR
Muscle contraction has been the focus of scientific investigation for more than two centuries, and major discoveries have changed the field over the years. Early in the twentieth century, Fenn (1924, 1923) showed that the total energy liberated during a contraction (heat + work) was increased when the muscle was allowed to shorten and perform work. The result implied that chemical reactions during contractions were load-dependent. The observation underlying the “Fenn effect” was taken to a greater extent when Hill (1938) published a pivotal study showing in details the relation between heat production and the amount of muscle shortening, providing investigators with the force-velocity relation for skeletal muscles. Subsequently, two papers paved the way for the current paradigm in the field of muscle contraction. Huxley and Niedergerke (1954), and Huxley and Hanson (1954) showed that the width of the A-bands did not change during muscle stretch or activation. Contraction, previously believed to be caused by shortening of muscle filaments, was associated with sliding of the thick and thin filaments. These studies were followed by the classic paper by Huxley (1957), in which he conceptualized for the first time the cross-bridge theory; filament sliding was driven by the cyclical interactions of myosin heads (cross-bridges) with actin. The original cross-bridge theory has been revised over the years but the basic features have remained mostly intact. It now influences studies performed with molecular motors responsible for tasks as diverse as muscle contraction, cell division and vesicle transport.