The interest in 'biomarkers' seen across a spectrum of biomedical disciplines reflects the rise of molecular biology and genetics. A host of 'omics' disciplines in addition to genomics, marked by multidimensional data and complex analyses, and enabled by bioinformatics, have pushed the trajectory of biomarker development even further. They have also made more tractable the complex mappings of genotypes to phenotypes - genome-to-phenome mapping - to which the concept of a biomarker is central. Genomic investigations of the brain are beginning to reveal spectacular associations between genes and neural systems. Neural and cognitive phenomics are considered a necessary complement to genomics of the brain. Other major omics developments such as connectomics, the comprehensive mapping of neurons and neural networks, are heralding brain maps of unprecedented detail. Such developments are defining a new era of brain science. And in this new research environment, neural systems and cognitive operations are pressed for new kinds of definitions - that facilitate brain-behavioral alignment in an omics operating environment. This volume explores the topic of markers framed around the constructs of cognitive and neural systems. 'Neurophenotype' is a term adopted to describe a neural or cognitive marker that can be scientifically described within an associative framework - and while the genome-to-phenome framework is the most recognized of these, epigenetics and non-gene-regulated neural dynamics also suggest other frameworks. In either case, the term neurophenotype defines operational constructs of brain-behavioral domains that serve the integration of these domains with neuroscientific and omics models of the brain. The topic is critically important to psychiatry and neuropsychology: Neurophenotypes offer a 'format' and a 'language' by which psychiatry and neuropsychology can be in step with the brain sciences. They also bring a new challenge to the clinical neurosciences in terms of construct validation and refinement. Topics covered in the volume include: Brain and cognition in the omics era Phenomics, connectomics, and Research Domain Criteria Circuit-based neurophenotypes, and complications posed by non-gene regulated factors The legacy of the endophenotype concept - its utility and limitations Various potential neurophenotypes of relevance to clinical neuroscience, including Response Inhibition, Fear Conditioning and Extinction, Error Processing, Reward Dependence and Reward Deficiency, Face Perception, and Language Phenotypes Dynamic (electrophysiological) and computational neurophenotypes The challenge of a cultural shift for psychiatry and neuropsychology The volume may be especially relevant to researchers and clinical practitioners in psychiatry and neuropsychology and to cognitive neuroscientists interested in the intersection of neuroscience with genomics, phenomics and other omics disciplines.

Mechanisms of neural plasticity enable the encoding and memorization of information based on sensory inputs and can be harnessed to partially restore function after CNS assault such as stroke or head trauma. In the present book, experts from the field of visual system plasticity describe and evaluate the evidence for neural mechanisms proposed to underlie CNS plasticity in the major divisions of the brain dedicated to visual processing, the retina, sub-cortical structures and cortex. We present studies from a wide variety of disciplines that range from molecular biology to neurophysiology and computer modeling. Leading investigators discuss their own work, and integrate this research with colleagues from other specializations. The book points out future applications for this research including clinical uses and engineering within the biomedical sciences. This book is an exciting and thought provoking read for all levels of science enthusiast interested in the physical basis of learning and cognition.

Since the introduction of fluorescent calcium indicators and the subsequent development of capacities for real-time monitoring and imaging of calcium movements in the intact cells studied in isolation, in situ and in vivo, the complex and vital calcium signaling system has been illuminated, proving calcium signals to be excellent universal reporters of cellular activity. In "Calcium Measurement Methods," a team of renowned experts in the field contribute methods dedicated to calcium imaging in neural cells with a balance between the main principles of calcium imaging and specific applications of the technique to neural tissues. The book's contents show how the combination of different indicators and recently developed microscopic techniques lead to spectacular successes in the imaging of neural cells in the living brain in both physiological and pathophysiological models. As a volume in the successful Neuromethods series, the chapters provide authoritative reviews including up-to-date detailed protocols of the most commonly used approaches in the field.

Cutting-edge and concise, "Calcium Measurement Methods" serves as an ideal reference to aid the many scientists worldwide engaged in calcium imaging of the nervous system."

High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identi?cation of leads is an essential part of drug discovery. The process for the identi?cation of leads generally starts with the screening of a compound collection, either an HTS of a relatively large compound collection (hundreds of thousands to one million plus compounds) or a more focused screen of a smaller set of compounds that have been preselected for the target of interest. Virtual screening methods such as structure-based or pharmacophore-based searches can complement or replace one of the above approaches. Once hits are identi?ed from one or more of these screening methods, they need to be thoroughly characterized in order to con?rm activity and identify areas in need of optimization. Finally, once fully characterized hits are identi?ed, preliminary optimization through synthetic modi?cation is carried out to generate leads. Parallel optimization of all properties, including biological, physicochemical, and ADME is the most ef?cient approach to the identi?cation of leads. Hit characterization is described in the previous chapter. The focus of this chapter is on hit optimization and the identi?- tion of leads. After a general overview of these processes, examples taken from the literature since 2001 will be used to illustrate speci?c points. There are also a number of excellent reviews covering the lead identi?cation process [1-6].

Singularity Hypotheses: A Scientific and Philosophical Assessment offers authoritative, jargon-free essays and critical commentaries on accelerating technological progress and the notion of technological singularity. It focuses on conjectures about the intelligence explosion, transhumanism, and whole brain emulation. Recent years have seen a plethora of forecasts about the profound, disruptive impact that is likely to result from further progress in these areas. Many commentators however doubt the scientific rigor of these forecasts, rejecting them as speculative and unfounded. We therefore invited prominent computer scientists, physicists, philosophers, biologists, economists and other thinkers to assess the singularity hypotheses. Their contributions go beyond speculation, providing deep insights into the main issues and a balanced picture of the debate.

Robotized Transcranial Magnetic Stimulation describes the methods needed to develop a robotic system that is clinically applicable for the application of transcranial magnetic stimulation (TMS). Chapter 1 introduces the basic principles of TMS and discusses current developments towards robotized TMS. Part I (Chapters 2 and 3) systematically analyzes and clinically evaluates robotized TMS. More specifically, it presents the impact of head motion on the induced electric field. In Part II (Chapters 3 to 8), a new method for a robust robot/camera calibration, a sophisticated force-torque control with hand-assisted positioning, a novel FTA-sensor for system safety, and techniques for direct head tracking, are described and evaluated. Part III discusses these developments in the context of safety and clinical applicability of robotized TMS and presents future prospects of robotized TMS. Robotized Transcranial Magnetic Stimulation is intended for researchers as a guide for developing effective robotized TMS solutions. Professionals and practitioners may also find the book valuable.

The field of stem cell biology is geared towards translation into clinical practice through in vitro tissue production and regeneration therapy. Since the discovery of adult neurogenesis, much attention has been put on the study of differentiation of stem cells into neural cell types and the development of model systems for stroke and neurodegenerative diseases.

In addition to chapters on therapeutic applicability of embryonic, very small-embryonic like, mesenchymal stem and neural progenitor cells, this book covers signalling mechanisms guiding induction to differentiation and cell diversification. Furthermore, fundamental aspects of stem cell biology and neurogenesis, such as the importance of proliferation induction, programmed cell death and the function of glia in differentiation of stem cells and development of neuronal circuits, are also highlighted. In vitro cultures of embryonic, mesenchymal and neural stem cells as well as mobilization of endogenous stem and precursor cells for brain repair and replacement therapy in neurological disorders are important issues of this book.

Each chapter is written by researchers who are leaders in the field and provides an invaluable resource for information on the most current advances in the field and possible therapeutic applications, with discussions of controversial issues and areas of emerging importance. By providing an up-to-date and critical view of the state of Science, we hope that this book shall be a base for exciting scientific ideas regarding functions and therapeutic applications of stem cells in the adult brain. The book is directed to neuroscientists, physicians, students and all who are engaged and interested in the exciting and rapidly expanding field of modern neuroscience and stem cell biology.

Efferent sensory systems have emerged as major components of processing by the central nervous system. Whereas the afferent sensory systems bring environmental information into the brain, efferent systems function to monitor, sharpen, and attend selectively to certain stimuli while ignoring others. This ability of the brain to implement these functions enables the organism to make fine discriminations and to respond appropriately to environmental conditions so that survival is enhanced. Our focus will be on auditory and vestibular efferents, topics linked together by the inner ear connection.

The biological utility of the efferent system is striking. How it functions is less well understood, and with each new discovery, more questions arise. The book that is proposed here reflects our vision to share what is known on the topic by authors who actually have made the observations.

This volume details methods for the analyses of specific lipid classes and lipidomics analyses of cells such as lymphocytes and oocytes. Lipidomics guides readers through chapters on direct-flow and chromatographic methods (SFC, UHPLC, HPTLC, ion-mobility); derivatization methods for lipids (amines, fatty aldehydes and ketones); TOF-SIMS imaging of lipids; and characterization of lipid transfer proteins. Additional chapters also provide an authoritative overview of lipidomics strategies and a detailed review of high-resolution mass spectrometric methods are included in this volume. In Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your own laboratory. Concise and easy-to-use, Lipidomics aims to ensure successful results in the further study of this vital field.

This volume contains information on the diagnosis, therapy, and prognosis of spinal tumors. Various aspects of different major types of spinal tumors (astrocytomas, ependymomas, and oligodendroglioma) are discussed. Insights into the understanding of molecular pathways involved in tumor biology are explained. Classification of intradural spinal tumors, including the percentages of each of the three major types, is detailed. Symptoms, radiological features, and clinicopathological parameters of spinal cord tumors are explained. Diagnosis, outcome, and prognosis of primary spinal cord and oligodendroglioma are discussed. Diagnosis of some other spinal tumors (e.g., pilomyxoid and chordomas) is also explained. The useful role of neuroimaging in diagnosing spinal teratoid/rhabdoid and gangliogliomas is included. A wide variety of treatments of a number of spinal cord tumor types are presented in detail. Therapies discussed include chemotherapy, surgery, radiosurgery, stereotactic radiosurgery, Cyberknife stereotactic radiotherapy, standard radiation alone, and rhenium-186 intracavity radiation. Also are duiscussed embolozation and spondylectomy. The usefulness of transplantation of human embryonic stem cells-derived oligodendrocyte progenitors and motoneuron progenitors in the repair of injured spinal cord is emphasized. Symptoms of the advent of spinal tumors are pointed out. Introduction to new technologies and their applications to spinal cord tumor diagnosis, treatment, and therapy assessment are explained.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

The Springer Handbook of Auditory Research presents a series of comprehensive and synthetic reviews of the fundamental topics in modern auditory research. The v- umes are aimed at all individuals with interests in hearing research including advanced graduate students, post-doctoral researchers, and clinical investigators. The volumes are intended to introduce new investigators to important aspects of hearing science and to help established investigators to better understand the fundamental theories and data in fields of hearing that they may not normally follow closely. Each volume presents a particular topic comprehensively, and each serves as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in pe- reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beg- ning to develop. New research areas will be covered on a timely basis in the series as they begin to mature.

This volume represents a valuable and readily reproducible collection of established and emerging techniques for neuronal cell death research. Conveniently divided into four parts, sections cover a series of techniques for the molecular, structural, functional and genomic characterization of dying neurons, a number of protocols that are of primary interest in neuropathology and in experimental neuropathology, a series of gene engineering techniques to obtain and manipulate neuronal stem cells and progenitors, to prepare HSV-1 vectors for the gene therapy, and to CNS transplantation of bone marrow stem cells, and finally, some very interesting protocols for the study of cell death in non-mammalian models. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Neuronal Cell Death: Methods and Protocols seeks to serve a large audience of scientists that are currently active in the field or are willing to enter such an exciting and still expanding area of neurobiology.

This text is an introduction to the interface between the actin cytoskeleton and the myriad of issues fundamental to the understanding of the nervous system. It covers the neurobiology of actin ranging from basic cellular organization and function to the roles of actin in the health and disease states of the nervous system. Its opening chapter presents the fundamental concepts required to appreciate the details of the molecular machinery that regulates actin in a cellular context, setting the stage for the first part of the book which reviews the neurobiology of actin at the cellular level. The latter section of the book then discusses the functions of actin in the context of neurobiological issues ranging from early development to synaptic function and disease states of the nervous system. This text is intended for neuroscientists interested in investigating the actin cytoskeleton in the context of their particular neuroscience research program, and its chapters are cross-referenced in order to assist readers in finding relevant information that is covered in greater depth in other chapters.

Muller glial cells ensheath all retinal neurons in vertebrate retinae. There are a multitude of functional interactions between neurons and Muller cells, including delivery of the light stimuli to the photoreceptor cells in the inverted vertebrate retina, a 'metabolic symbiosis' with the neurons, and the processing of visual information. Muller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neuro-transmitter molecules, and pH). In vascularized retinae, Muller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Muller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration:

Muller cells protect neurons via a release of neurotrophic factors. However, gliotic Muller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Muller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Muller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina.

Muller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (i.e. somatic gene therapy), or to differentiate retinal neurons from Muller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Muller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/-protective - and prevent the destructive - mechanisms of gliosis.

Oral tolerance is a major immunological property of the gastrointestinal mucosa. It plays a critical role in immune defence by preventing inflammatory and allergic responses to dietary and non pathogenic microbial antigens. The interest in oral tolerance has been renewed in the recent years, due to novel insights on its cellular mechanisms and potential clinical applications in the treatment of autoimmune diseases.
Oral Tolerance: Cellular and Molecular Basis, Clinical Aspects, and Therapeutic Potential, has been designed as a concise yet comprehensive overview of the newest fundamental and clinical advances in the field. Based on the outstanding contribution of world experts, this book will be helpful to students, clinicians, and researchers working in mucosal immunology and gastroenterology.
The first part of this volume describes the structure and functions of the gastrointestinal mucosa and the fundamental features and mechanisms of oral tolerance, including the role of T cells, cytokines, IgA antibodies, and bacterial antigens. The second part explores the clinical implications of the disruption of oral tolerance in Inflammatory Bowel Diseases, food and milk allergies, and coeliac disease in particular. The final chapter focuses on the clinical potential of oral tolerance as a promising therapeutic tool.

Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research.
This volume is a collection of chapters covering recent advances in the field of neurobiology. Chapters address anesthetic binding sites on the nicotinic acetylcholine receptors, NMDA receptor signal regulation, alcohol self-administration in rodents, and dopamine receptor mutations in mice.
Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research.
This volume is a collection of chapters covering recent advances in the field of neurobiology. Chapters address anesthetic binding sites on the nicotinic acetylcholine receptors, NMDA receptor signal regulation, alcohol self-administration in rodents, and dopamine receptor mutations in mice.

The function of vertebrate hearing is served by a surprising variety of sensory structures in the different groups of fish, amphibians, reptiles, birds, and mammals. This book discusses the origin, specialization, and functional properties of sensory hair cells, beginning with environmental constraints on acoustic systems and addressing in detail the evolutionary history behind modern structure and function in the vertebrate ear. Taking a comparative approach, chapters are devoted to each of the vertebrate groups, outlining the transition to land existence and the further parallel and independent adaptations of amniotic groups living in air. The volume explores in depth the specific properties of hair cells that allowed them to become sensitive to sound and capable of analyzing sounds into their respective frequency components. Evolution of the Vertebrate Auditory System is directed to a broad audience of biologists and clinicians, from the level of advanced undergraduate students to professionals interested in learning more about the evolution, structure, and function of the ear.

The main topic of the book is a reconstruction of the evolution of nervous systems and brains as well as of mental-cognitive abilities, in short "intelligence" from simplest organisms to humans. It investigates to which extent the two are correlated. One central topic is the alleged uniqueness of the human brain and human intelligence and mind. It is discussed which neural features make certain animals and humans intelligent and creative: Is it absolute or relative brain size or the size of "intelligence centers" inside the brains, the number of nerve cells inside the brain in total or in such "intelligence centers" decisive for the degree of intelligence, of mind and eventually consciousness? And which are the driving forces behind these processes? Finally, it is asked what all this means for the classical problem of mind-brain relationship and for a naturalistic theory of mind.

This book illustrates remarkable roles of metal ions in the neuropathophysiology of stroke, which is a major cause of death and disability worldwide. Metal ions have unique chemical properties that allow them to play diverse roles in the brain. They regulate excitability and function as co-factors in cellular and genetic signaling pathways and therefore, have important roles ranging from essential to toxic. For the first time, the dyshomeostasis and pathophysiological actions of these metals in stroke are discussed systematically in thirty-six chapters in one volume. Highlighted metal ions include: Aluminum (Al) Arsenic (As) Cadmium (Cd) Calcium (Ca) Copper (Cu) Iron (Fe) Magnesium (Mg) Manganese (Mn) Mercury (Hg) Nickel (Ni) Potassium (K) Selenium (Se) Sodium (Na) Zinc (Zn)

The Springer Handbook of Auditory Research presents a series of compreh- sive and synthetic reviews of the fundamental topics in modern auditory - search. The volumes are aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes are intended to introduce new investigators to important aspects of hearing science and to help established investigators to better understand the fundamental theories and data in ?elds of hearing that they may not normally follow closely. Each volume presents a particular topic comprehensively, and each serves as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature.

Why do minds exist? How did mud and stone develop into beings that can experience longing, regret, love and compassion-beings that are aware of their own experience? Until recently, science offered few answers to these existential questions. Journey of the Mind is the first book to offer a unified account of the mind that explains how consciousness, language, the Self and civilisation emerged incrementally out of chaos. The journey begins three billion years ago with the emergence of the simplest possible mind, a nanoscopic archeon, then ascends through amoebas, worms, frogs, birds, monkeys and AI, examining successively smarter ways of thinking. The authors explain the mathematical principles generating conscious experience and show how these principles led cities and democratic nations to develop new forms of consciousness-the self-aware "superminds". Journey of the Mind concludes by contemplating a higher stage of consciousness already emerging-and the ultimate fate of all minds in the universe.

Dr. Elisabeth Bock (Photo Keenpress) This book contains review articles that produce a snapshot of recent developments in the field of the neural cell adhesion molecule NCAM. The chapters are grouped into sections reflecting various aspects of NCAM structure and function. The themes cover the structural basis of cell adhesion mediated by NCAM and NCAM interaction partners, NCAM-mediated signaling determinants of NCAM function under physiological conditions and in disease, and the therapeutic potential of NCAM mimetics. Section 1, "Structure and Ligands of NCAM," introduces the reader to the str- tural basis of NCAM-mediated cell adhesion, discussing the current knowledge of extracellular and intracellular NCAM ligands and the structural basis of NCAM int- actions with the fibroblast growth factor (FGF) receptor. Section 2, "NCAM and Polysialic Acid," focuses on NCAM polysialylation, discussing the structural and functional aspects of the most important posttranslational modifications of NCAM by the addition of a long linear homopolymer of sialic acid to the fifth Ig-like NCAM module. Section 3, "NCAM-mediated Signal Transduction," is devoted to signal v BookID 187530_ChapID FM1_Proof# 1 - 01/03/2011 BookID 187530_ChapID FM1_Proof# 1 - 01/03/2011 vi Preface transduction mechanisms associated with NCAM-mediated adhesion, with a focus on signaling pathways involved in NCAM-mediated neurite outgrowth, the role of growth-associated proteins, signaling through lipid microdomains, and signaling crosstalk with the epidermal growth factor (EGF) receptor. Section 4, "NCAM Metabolism," focuses on current knowledge about NCAM biosynthesis and the g- eration and role of soluble NCAM.