Gabriel Waksman Institute of Structural Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, United Kingdom Address for correspondence: Professor Gabriel Waksman Institute of Structural Molecular Biology Birkbeck and University College London Malet Street London WC1E 7H United Kingdom Email: g. waksman@bbk. ac. uk and g. waksman@ucl. ac. uk Phone: (+44) (0) 207 631 6833 Fax: (+44) (0) 207 631 6833 URL: http://people. cryst. bbk. ac. uk/?ubcg54a Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of Structural Molecular Biology at UCL/Birkbeck, of which he is also the director. Before joining the faculty of UCL and Birkbeck, he was the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine in St Louis (USA). The rapidly evolving ?eld of protein science has now come to realize the ubiquity and importance of protein-protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of hi- throughput proteomics to monitor protein-protein interactions at an organism level, we can now safely state that protein-protein interactions are the norm and not the exception.

This book collects articles on the biology of hematopoietic stem cells during embryonic development, reporting on fly, fish, avian and mammalian models. The text invites a comparative overview of hematopoietic stem cell generation in the different classes, emphasizing conserved trends in development. The book reviews current knowledge on human hematopoietic development and discusses recent breakthroughs of relevance to both researchers and clinicians.

This volume will explore the most recent findings on cellular mechanisms of inhibitory plasticity and its functional role in shaping neuronal circuits, their rewiring in response to experience, drug addiction and in neuropathology. Inhibitory Synaptic Plasticity will be of particular interest to neuroscientists and neurophysiologists.

This book summarizes 20 years of work on the kinetics of blood-brain transfer and metabolism mechanisms in mammalian brain. The substances affiliated with these mechanisms include glucose, amino acids, monocarboxylic acids, and oxygen. These substances are important to energy metabolism and neurotransmission in the mammalian brain at rest and during activation. To understand the processes addressed by these mechanisms, the book examines the kinetics of compartmentation and compartmental analysis, particularly as they relate to transporter, enzyme, and receptor function. Compartments are subsets of substances separated by transporters and receptors in membranes, and enzymes in cells. This book is divided in six major chapters covering compartmental analysis, kinetic analysis of transport and metabolism, blood-brain transfer and metabolism of glucose, amino acids, and oxygen, and amino acid metabolism and interaction of amino acid metabolites with receptors.

The book "Paradigm Shift for Future Tennis" starts with revelations that make obvious the limitations of today's tennis, which does not use the laws of modern Biomechanics and Neurophysiology. The second part of the book includes a new approach to the quantum mind of a champion. It will reveal the secret weapon of Roger Federer and the blueprint of a future tennis champion. This book will expose the new tennis shot emerging from the field of sports science. It is a real weapon, which can generate a ball-speed similar to that of the first serve: the Power High-Forehand. Its aim is to generate maximal possible racket-head speed while players do not wait for the ball to bounce. This is both a tactical and psychological basis for the future tennis game. This aggressive interceptive psychology will shape the minds of future tennis champions. High racket-head speed can be achieved using the stretch-reflex, without big loops and swings. Weapons of a future tennis game will comprise of whip-like tennis serves and ground strokes, based on the stretch-reflex, and using the whole body in a fluid and integrated manner, thus manifesting a superb combination of speed and strength. Restructure your brain and apply the power of state of the art biomechanical, mathematical, medical, neural, cognitive, and quantum computational intelligence to understand the tennis of today and the future!

Increasing interest in the study of coordinated activity of brain cell ensembles reflects the current conceptualization of brain information processing and cognition. It is thought that cognitive processes involve not only serial stages of sensory signal processing, but also massive parallel information processing circuitries, and therefore it is the coordinated activity of neuronal networks of brains that give rise to cognition and consciousness in general. While the concepts and techniques to measure synchronization are relatively well characterized and developed in the mathematics and physics community, the measurement of coordinated activity derived from brain signals is not a trivial task, and is currently a subject of debate. Coordinated Activity in the Brain: Measurements and Relevance to Brain Function and Behavior addresses conceptual and methodological limitations, as well as advantages, in the assessment of cellular coordinated activity from neurophysiological recordings. The book offers a broad overview of the field for investigators working in a variety of disciplines (neuroscience, biophysics, mathematics, physics, neurology, neurosurgery, psychology, biomedical engineering, computer science/computational biology), and introduces future trends for understanding brain activity and its relation to cognition and pathologies. This work will be valuable to professional investigators and clinicians, graduate and post-graduate students in related fields of neuroscience and biophysics, and to anyone interested in signal analysis techniques for studying brain function.

Unraveling the functional properties of structural elements in the brain is one of the fundamental goals of neuroscientific research. In the cerebral cortex this is no mean feat, since cortical areas are defined microstructurally in post-mortem brains but functionally in living brains with electrophysiological or neuroimaging techniques - and cortical areas vary in their topographical properties across individual brains. Being able to map both microstructure and function in the same brains noninvasively in vivo would represent a huge leap forward. In recent years, high-field magnetic resonance imaging (MRI) technologies with spatial resolution below 0.5 mm have set the stage for this by detecting structural differences within the human cerebral cortex, beyond the Stria of Gennari. This provides the basis for an in vivo microanatomical brain map, with the enormous potential to make direct correlations between microstructure and function in living human brains. This book starts with Brodmann's post-mortem map published in the early 20th century, moves on to the almost forgotten microstructural maps of von Economo and Koskinas and the Vogt-Vogt school, sheds some light on more recent approaches that aim at mapping cortical areas noninvasively in living human brains, and culminates with the concept of "in vivo Brodmann mapping" using high-field MRI, which was introduced in the early 21st century.

The human immune system is a complex network of tissues and organs dispersed throughout the body. Immunology, as one of the most rapidly evolving fields in biomedical research, has to date covered the essential cellular and molecular events necessary for immune responses to occur. However, it has paid relatively little attention to important developmental processes underlying the formation of the tissues themselves that carry out immune responses in humans and other mammalians. In contrast to the thymus and bone marrow that are the sole tissues for generating mature leukocytes for antigen recognition and handling in humans and most mammalian species, the peripheral lymphoid tissues where adaptive immune responses are focused display broad tissue distribution and possess diverse architectural characteristics. These organs develop prior to the individual's exposure to external antigens, and despite their similar functions, their varied appearances indicate a substantial complexity of tissue ontogeny. This volume presents a comprehensive overview of the developmental features of the major peripheral lymphoid organs, thus examining the connection between immunological functionality and structural characteristics utilizing a developmental approach, for an audience ranging from undergraduate students to senior researchers in immunology, histology and clinical medicine.

The study and modulation of cortical connections is a rapidly growing area in neuroscience. This unique book by prominent researchers in the field covers recent advances in this area. The first section of the book describes studies of cortical connections, modulation of cortical connectivity and changes in cortical connections with activities such as motor learning and grasping in primates. The second section covers the use of non-invasive brain stimulation to study and modulate cortical connectivity in humans. The last section describes changes in brain connectivity in neurological and psychiatric diseases, and potential new treatments that manipulate brain connectivity. This book provides an up-to-date view of the study of cortical connectivity, and covers its role in both fundamental neuroscience and potential clinical applications.

GABA (gamma-aminobutyric acid) is the main neurotransmitter regulating sleep. The majority of drugs presently in use for the treatment of sleep disorders act by enhancing GABAergic neuronal inhibition. The GABA system is, therefore, of prime clinical relevance for the therapy of insomnia. The focus of this volume is on the neuropsychopharmacology and the clinical impact of the GABA system in regulating sleep and wakefulness. It presents molecular, neuropharmacological, systems-biological and clinical approaches to the understanding of the mechanism of action of GABA and GABAergic drugs. It also explores the role of GABA in the basic drives that affect sleep, and the influences that adapt sleep and wakefulness to external events.

Pediatric Injury Biomechanics: Archive and Textbook consolidates and describes the current state of the art in pediatric injury biomechanics research in the automotive crash environment. Written by the most respected scientists in the field, the objective of this ground-breaking project is to provide a comprehensive archive and analysis of pediatric injury biomechanics research; to be the go-to reference for the epidemiology of motor vehicle related childhood injury data, pediatric anthropometry, pediatric biomechanical properties, tissue tolerance, and computational models. This book provides essential information needed by researchers working in the field of pediatric injury including those involved in rulemaking activities, injury criteria development, child dummy development, and child injury interventions development. In addition to the text, a companion archive will include valuable information and tools to assist in the identification of gaps in research and future research directions.This living document will be regularly updated with current research and advancements in pediatric injury biomechanics.

From the 39th annual conference of the International Society on Oxygen Transport to Tissue (ISOTT), held in Washington, DC, USA in July 2011, this volume covers aspects of oxygen transport from air to the cells, organs and organisms; instrumentation and methods to sense oxygen and clinical evidence. Oxygen Transport to Tissue XXXIV includes contributions from scientists (physicists, biologists and chemists), engineers, clinicians and mathematicians.

The term humanized mouse in this text refers to a mouse in which human tissues and cells have been transplanted and show the same biological function as they do in the human body. That is, the physiological properties and functions of tra- planted human tissues and cells can be analyzed in the mouse instead of using a living human body. It should therefore be possible to study the pathophysiology and treatment of human diseases in mice with good reproducibility. Thus, the hum- ized mouse can be used as a potent tool in both basic and clinical research in the future. The development of appropriate immunodeficient mice has been indispensable in the creation of the humanized mouse, which has been achieved through many years of efforts by several laboratories. The first stage on the road to the humanized mouse was the report on nude mice by Isaacson and Cattanach in 1962. Thereafter, nude mice were studied in detail by Falanagan and, in 1968, Pantelouris found that these mice have no thymus gland, which suggested that the mice lack transplan- tion immunity against xenografts such as human hematopoietic stem cells. At the Nude Mouse Workshops (organized by Regard, Povlsen, Nomura and colleagues) that were held nine times between 1972 and 1997, the possibility of creating a humanized mouse using nude mice was extensively examined. The results, however, showed that certain human cancers can be engrafted in nude mice, but unfortunately engraftment of normal human tissue was almost impossible.

Growth is a complex process that is essential to life. Not only does size play an important role in the process of cellular proliferation, but body size is also a critical factor in determining which organisms live longer. Evolution has been characterised by a dramatic increase in an organism's body size, which is not only limited to the size of the brain.

Signal Transduction in Cardiovascular System Health and Disease highlights the major contributions of different signaling systems in modulating normal cardiovascular functions and how a perturbation in these signaling events leads to abnormal cell functions and cardiovascular disorders. This title is volume 3 in the new Springer series, Advances in Biochemistry in Health and Disease.

Since its ?rst description in 1942 in both serum and cerebrospinal ?uid, transthyretin (TTR) has had an eventful history, including changes in name from "prealbumin" to "thyroxine-binding prealbumin" to "transthyretin" as knowledge increased about its functions. TTR is synthesised in a wide range of tissues in humans and other eutherian mammals: the liver, choroid plexus (blood- cerebrospinal ?uid barrier), retinal pigment epithelium of the eye, pancreas, intestine and meninges. However, its sites of synthesis are more restricted in other vertebrates. This implies that the number of tissues synthesising TTR during vertebrate evolution has increased, and raises questions about the selection pressures governing TTR synthesis. TTR is most widely known as a distributor of thyroid hormones. In addition, TTR binds retinol-binding protein, which binds retinol. In this way, TTR is also involved with retinoid distribution. More recently, TTR has been demonstrated to bind a wide variety of endocrine disruptors including drugs, pollutants, industrial compounds, heavy metals, and some naturally occurring plant ?avonoids. These not only interfere with thyroid hormone delivery in the body, but also transport such endocrine disruptors into the brain, where they have the potential to accumulate.

Pregnancy, childbirth, childhood, adolescence, and aging can be beset with adverse changes in psychobiology and behavior. Handbook of Lifespan Cognitive Behavioral Therapy: Childhood, Adolescence, Pregnancy, Adulthood, and Aging will better readers' understanding of a variety of conditions and the applicability of CBT therapy as a treatment. Featuring chapters on postnatal anxiety and depression, insomnia, and dysmorphia, the book discusses in detail the use of cognitive behavioral therapies in the treatment of these issues affecting individuals at the start and end of their lives. With expert authors from the clinical field, the book has applicability for behavioral scientists, psychologists, cognitive and behavioral neuroscientists, and anyone working to better understand and treat using cognitive behavioral therapies.

This volume synthesizes pathways in respiratory mechanics and the dynamics of air-blood and blood-cellular gas exchange for students and teachers in respiratory physiology. The authors strive to make physiology fun to learn. This aspect of knowledge acquisition is reflected in the way topics are approached, for example by using playing cards in what is coined 'Respi-CARDology'. The first section of this book reviews the framework and foundations of basic respiratory physiology. Since this book was not written to be a comprehensive physiology text, the authors have focused on leading students to appreciate and understand integrative principles and homeostatic mechanisms in lung function. The second section of this book mainly deals with the clinical application of fundamental knowledge of respiratory physiology.

Developmental genetic studies of the spine and linkage and family-based association studies have led to recent advances in understanding the genetic etiology of idiopathic, neuromuscular, and congenital forms of scoliosis. The book is written by leaders in genetic and developmental research on scoliosis and developmental studies of the spine.

Regeneration, the homeostatic ability to maintain tissue structure in the face of normal cell turnover or loss of tissue damaged by trauma or disease, is an essential developmental process that continues throughout life. As recently as a decade ago, any serious discussion of the possibility of regeneration becoming a practical medical tool in the near future had the air of science fiction or over-optimistic speculation. The term "regenerative medicine" was certainly on many lips but few actually expected to soon see it applied in a clinical setting. A tidal wave of discovery has changed that and investigating the cellular mechanisms of natural regeneration has become one of the hottest topics in developmental biology and biomedicine in general. Many researchers entering the field find that the regeneration literature is still quite diffuse perhaps owing to the disparate biological systems that have been the object of study including hydra, planaria, newts, axolotls and more recently several mouse strains. The volume editors believe that an attempt to organize or systematize the literature is long overdue. In this volume, respected experts highlight the latest findings in vertebrate (including mammals) wound healing and regeneration. They present eleven reviews that cover a wide range of topics, from wound repair and its relationship to regeneration, through systems including lenticular, neural, and musculoskeletal tissues and limbs, to epigenetics and the role of the cell cycle. Nuclear reprogramming and cellular plasticity, which open the door for potential regenerative medical therapies for injury and degenerative disease, are recurring themes throughout the book. We are all now part of the regeneration revolution.

The volume raises attention to the need of a completely new approach to breast cancer based on the knowledge collected on early breast cancer in the past two decades. The chapters are contributed by experts of all the fields participating in the clinical research and care of breast cancer. The practical importance of such a book is underlined by the increasing number of breast cancer cases, and also the increasing proportion of early stage-cases. The ultimate goal of the book is to point to the heterogeneous nature of the disease which is more striking and has more importance in care at the very early stages than at the more advanced stages. The book recommends the utilization of all the information provided by multimodality imaging and special pathological methods, a new classification system and therapeutic guidelines since early breast cancers should not be treated based on experience obtained with palpable tumors. No similar book has been yet released to the market. The book is written for all the members of the team participating in the diagnosis and treatment of breast cancer (radiologists, pathologists, surgeons, clinical and radiation oncologists), but may be useful for medical students and residents too. The chapters are illustrated with didactic pictures, and special emphasis is given to provide a peep into the practice of the special procedures for the careful examination and individualized therapy of each case.

Biomechanics applies the principles and rigor of engineering to the mechanical properties of living systems. This book integrates the classic fields of mechanics--statics, dynamics, and strength of materials--using examples from biology and medicine. Fundamentals of Biomechanics is excellent for teaching either undergraduates in biomedical engineering programs or health care professionals studying biomechanics at the graduate level. Extensively revised from a successful first edition, the book features a wealth of clear illustrations, numerous worked examples, and many problem sets. The book provides the quantitative perspective missing from more descriptive texts, without requiring an advanced background in mathematics. It will be welcomed for use in courses such as biomechanics and orthopedics, rehabilitation and industrial engineering, and occupational or sports medicine.

Of the approximately 640 muscles in the human body, over 10% of them are found in the craniofacial region. The craniofacial muscles are involved in a number of crucial non-locomotor activities, and are critical to the most basic functions of life, including vision, taste, chewing and food manipulation, swallowing, respiration, speech, as well as regulating facial expression and controlling facial aperture patency. Despite their importance, the biology of these small skeletal muscles is relatively unexplored. Only recently have we begun to understand their unique embryonic development and the genes that control it and characteristic features that separate them from the skeletal muscle stereotype. This book is the most comprehensive reference to date on craniofacial muscle development, structure, function, and disease. It details the state-of-the-art basic science of the craniofacial muscles, and describes their unique response to major neuromuscular conditions. Most importantly, the text highlights how the craniofacial muscles are different from most skeletal muscles, and why they have been viewed as a distinct allotype. In addition, the text points to major gaps in our knowledge about these very important skeletal muscles and identified key gaps in our knowledge and areas primed for further study and discovery.

Research into gastrointestinal motility has received renewed interest in part due to recent advances in the techniques for measuring the structure and function of gastrointestinal cells, tissue and organs. The integration of this wealth of data into biophysically based computation models can aid in interpretation of experimental and clinical measurements and the refinement of measurement techniques. The contents of this book span multiple scales - from cell, tissue, organ, to whole body and is divided into four broad sections covering: i) gastrointestinal cellular activity and tissue structure; (ii) techniques for measuring, analyzing and visualizing high-resolution extra-cellular recordings; (iii) methods for sensing gastroelectrical activity using non-invasive bio-electro-magnetic fields and for modulating the underlying gastric electrical activity and finally (iv) methods for assessing manometric and videographic motility patterns and the application of these data for predicting the flow and mixing behavior of luminal contents by using computational fluid dynamic techniques. This book aims to provide both an overview of historical and existing research techniques as well as to highlight future directions and challenges for the community as a whole. It will be suitable for clinicians to understand the cellular and biophysical underpinnings of gastric emptying, gastroenterologists, surgeons, bioengineers and all scientists with interests in gastrointestinal motility research.