Chromosomes, as the genetic vehicles, provide the basic material for a large proportion of genetic investigations, from the construction of gene maps and models of chromosome organization, to the inves tigation of gene function and dysfunction. The study of chromosomes has developed in parallel with other aspects of molecular genetics, beginning with the first preparations of chromosomes from animal cells, through the development of banding techniques, which permitted the unequivocal identification of each chromosome in a karyotype, to the present analytical methods of molecular cytogenetics. Although some of these techniques have been in use for many years, and can be learned relatively easily, most published scientific reports-as a result of pressure on space from editors, and the response to that pressure by authors-contain little in the way of technical detail, and thus are rarely adequate for a researcher hoping to find all the necessary information to embark on a method from scratch. A new user needs not only a detailed description of the methods, but also some help with problem solving and sorting out the difficulties en countered in handling any biological system. This was the require ment to which the series Methods in Molecular Biology is addressed, and Chromosome Analysis Protocols forms a part of this series.

Recent research, which Bone- Metabolic Function and Modulators expands on, has added new support to the idea that bone not only serves as a support system, but also functions as an integrating organ, with a significant regulatory role for lipid and energy metabolism. Links between physical activity and the skeleton are also becoming increasingly clear. This fully illustrated volume contains up-to-date information on the metabolic role of the skeleton and what this can mean for the treatment of metabolic as well as skeletal and auditory diseases. Bone- Metabolic Function and Modulators is of particular interest to clinician scientists, clinical and basic bone researchers, orthopedists, endocrinologists, internists, dentists, nurse practitioners, medical and dental residents and physiotherapists as well as students of the musculoskeletal system. Bone- Metabolic Function and Modulators is the seventh volume in the series Topics in Bone Biology, edited by Felix Bronner and Mary C. Farach-Carson. Other titles in this series:- Bone Formation Bone Resorption Engineering of Functional Skeletal Tissues Bone and Osteoarthritis Bone and Cancer Bone and Development Bone- Metabolic Function and Modulators is of particular interest to clinician scientists, clinical and basic bone researchers, orthopedists, endocrinologists, internists, dentists, nurse practitioners, medical and dental residents and physiotherapists as well as students of the musculoskeletal system. Bone- Metabolic Function and Modulators is the seventh volume in the series Topics in Bone Biology, edited by Felix Bronner and Mary C. Farach-Carson. Other titles in this series:- Bone Formation Bone Resorption Engineering of Functional Skeletal Tissues Bone and Osteoarthritis Bone and Cancer Bone and Development Bone- Metabolic Function and Modulators is of particular interest to clinician scientists, clinical and basic bone researchers, orthopedists, endocrinologists, internists, dentists, nurse practitioners, medical and dental residents and physiotherapists as well as students of the musculoskeletal system. Bone- Metabolic Function and Modulators is the seventh volume in the series Topics in Bone Biology, edited by Felix Bronner and Mary C. Farach-Carson. Other titles in this series:- Bone Formation Bone Resorption Engineering of Functional Skeletal Tissues Bone and Osteoarthritis Bone and Cancer Bone and Development

calcium exchanger, which is the topic of the final chapter of the book by N. Gabellini, A. Zatti, and E. Carafoli. Padova Zurich, Ernesto Carafoli February 2000 Joachim Krebs "Yes, calcium, that is everything ..." Contents Calcium Homeostasis and Its Evolution Robert J. P. Williams ...Evolution of EF-Hand Proteins Susumu Nakayama, Hiroshi Kawasaki and Robert Kretsinger...29 . Calmodulin Target Recognition: Common Mechanism and Structural Diversity Tao Yuan, Kyoko L. Yap and Mitsuhiko Ikura ...59 ...Calcium-Binding EGF-like Domains A. K. Downing, P. A. Handford and J. D. Campbell...83 ...Calmodulin-Dependent Protein Kinases Joachim Krebs...101 ...Structure of Calcineurin and Its Complex with Immunophilins Claude B. Klee ...125 ...2 The Ca + Pump of Sarcoplasmic and Endoplasmic Reticulum Membranes Giuseppe Inesi and Chikashi Toyoshima...143 ...2 The Plasma Membrane Ca + ATPase Danilo Guerini ...155 ...2 The Na+/Ca+ Exchanger: Structural Aspects, Function and Regulation Nadia Gabellini, Alessandra Zatti and Ernesto Carafoli ...173 ...Calcium Homeostasis and Its Evolution Robert J. P. Williams Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OXl 3QR, UK E-mail: Susie. Compton@chem. ox. ac. uk The homeostasis of calcium is managed very differently in different organisms. A general outline of homeostasis, a dynamic balanced flow, is therefore described before a description of the systems in particular classes of organism. The organisms are treated in the sequence: prokaryotes, single-cell eukaryotes and, lastly, multicellular organisms reaching up to man.

Dr. Howard House, founder of the House Ear Institute and House Ear Clinic often uses the analogy of planting a seed when referring to establishing the House Ear Institute in 1946. Two grateful patients of Dr. House put forth the idea that his knowledge and innovative skills could be used to expand the understanding of hearing impairment and its treatment. Those two early patients provided the "seed money" to begin the Institute. Since that time, the growth has been phenomenal from a one-man laboratory to a multidisciplinary facility boasting over 175 scien tists, physicians, and support staff, all dedicated to the advancement of otologic research and education. Six years ago after a half-century of remarkable success with prosthetic and device research, the Institute began cultivating a new field of endeavor-cell and molecular biology. Don Nielsen, then the Institute's Executive Vice President for Research and Scientific Director, began exploring the potential for hair cell regen eration and presented his ideas to the Board of Trustees. For a period of six months, we did a lot of fact finding to assess what role the Institute might take in this excit ing new field."

The goal of Biological Aging: Methods and Protocols is to present some of the most promising and important tools that are currently used in biological aging research. These tools include established protocols such as aging cell culture as well as many more contemporary approaches such as nuclear transfer, microarray and proteomics technologies and the use of ribozymes in aging research. Collectively, these powerful tools combined with the many other techniques that are presented are rapidly advancing the exciting and expanding field of biological aging.

Proceedings of the 5th Biannual International Meeting on Angiogenesis: From the Molecular to Integrative Pharmacology, held July 1-7, 1999, in Crete, Greece. Angiogenesis, as a vastly complex biological process, has challenged researchers from all basic scientific disciplines, including pharmacology, biochemistry, physiology, embryology and anatomy. The significance of this phenomenon for the study of disease states has also interested clinicians from a number of specialist fields. This multidisciplinary work reflects the growth of awareness of concepts such as angiogenesis based therapy, the enormous therapeutic and commercial potential of which has attracted major research and investment in recent years. This volume, which aims to bridge the gap between basic and clinical methodology and understanding, presents the most up-to-date developments in this field.

Following systematic development of technical aspects and physiological understanding, and clinical applicability of cardiac autonomic testing, this book provides a detailed guide to performing individual autonomic tests in both research and clinical settings. The book is structured in three parts covering the physiological background of cardiac autonomic regulations, description of technology and interpretation of individual autonomic tests, and applicability of the individual tests under various clinical circumstances and in defined populations of patients. The book is intended to serve both research and clinical cardiologists as well as research and clinical specialists of other medical fields who use the assessment of cardiac modulations to investigate the autonomic nervous system.

During several decades of this century, the classical physiological studies on the cardiovascular system have greatly improved our knowledge on the function of this system under normal and pathological conditions. This knowledge was the basis of the breakthrough for diagnostic techniques like the Swan-Ganz catheter, coronary arteriography, left and right heart biopsies, and invasive measurements of contractility, as well as therapeutic tools including aortocoronary bypass surgery, percutanous transluminal coronary angioplasty, and a broad field of pharmacological interventions for the whole spectrum of cardiovascular diseases, especially chronic heart failure. It was during the last decade that the scientific world focused on the evolution of molecular biology of the cardiovascular system so that cardiovascular physiology seemed to become less important. Regarding the myocardium, molecular alterations of important functional proteins (phenotype changes), as well as signal transduction pathways of contractility and cardiac growth have been elucidated. The functional importance of a number of genes has undoubtedly been proven with the help of transgenic animals. Mechanics and Energetics of the Myocardium provides an overview for those researchers and practioners interested in the broad field of molecular biology and physiology of the cardiovascular system.

In the coming decade, the focus of medicine will shift from a disease-oriented approach, where the physician prescribes according to the disease the patient has, to a personalized approach, in which the physician first considers the patient's individual biochemistry before prescribing a treatment. Personalized medicine has the potential to improve efficacy and safety in virtually all fields of medicine. Unfortunately, few physicians feel confident in their ability to apply the principles of genetics and genomics upon which personalized medicine is based to their practice. This book is intended to help the practicing physician understand and apply the principles of genetic and genomic medicine, regardless of his/her level of background in the field. It provides a thorough foundation/review of classical genetic principles, with an emphasis on how these principles apply to personalized medicine and common complex diseases. In addition, it provides a wide-ranging review of the inroads that personalized medicine has made into several fields, including cancer, psychiatric disorders, cardiovascular disease, substance abuse, Alzheimer disease, respiratory diseases, type 2 diabetes and macular degeneration. Most importantly, this book is intended to enable the practicing physician, physician assistants and their entire healthcare team to anticipate the developments that will emerge in the near future, and stay current with the field as it expands.

Most routine motor tasks are complex, involving load transmission through out the body, intricate balance, and eye-head-shoulder-hand-torso-leg coor dination. The quest toward understanding how we perform such tasks with skill and grace, often in the presence of unpredictable perturbations, has a long history. This book arose from the Ninth Engineering Foundation Con ference on Biomechanics and Neural Control of Movement, held in Deer Creek, Ohio, in June 1996. This unique conference, which has met every 2 to 4 years since the late 1960s, is well known for its informal format that promotes high-level, up-to-date discussions on the key issues in the field. The intent is to capture the high quality ofthe knowledge and discourse that is an integral part of this conference series. The book is organized into ten sections. Section I provides a brief intro duction to the terminology and conceptual foundations of the field of move ment science; it is intended primarily for students. All but two of the re maining nine sections share a common format: (l) a designated section editor; (2) an introductory didactic chapter, solicited from recognized lead ers; and (3) three to six state-of-the-art perspective chapters. Some per spective chapters are followed by commentaries by selected experts that provide balance and insight. Section VI is the largest section, and it con sists of nine perspective chapters without commentaries."

Recent work has revealed that stabilizing G-quadruplexes in telomeric DNA inhibits telomerase activity, providing impetus for the development of G-quartet-interacting drugs, while G-quartet-containing oligonucleotides have been recognized as a potent class of aptamers effective against STAT3 and other transcription factors implicated in oncogenesis, proving these guanine-quartets to be a vital and rich area for future study. In "G-Quadruplex DNA: Methods and Protocols", experts in the field present a collection of detailed techniques for studying G-quartet formation, dynamics, and molecular recognition. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, "G-Quadruplex DNA: Methods and Protocols "promises to be a useful resource for those familiar with G-quartets as well as an easy entry point for those researchers from diverse fields who are just developing an interest in the exciting implications of G-quadruplex DNA.

As humans ventured into the twentieth century, the industrialized countries were confronted with the scourge of rickets. Although solariums were becoming common in the early 1900s and phototherapy was gaining popularity as a result of the awarding of a Nobel Prize to Finsen in 1903, it wasn't until 1921 when Hess and Unger demonstrated that rickets could be cured by exposure to sunlight that the healthful benefit of sun exposure appreciated. In 1941, Apperly (Cancer Research; 1: 191-195, 1941) noted that the occasional increased risk of skin cancer was associated with a decreased risk of many other more common and serious cancers. The alarming increase in the number of cases of skin cancer, especially melanoma, has caused great concern about the negative role of sunlight in health. The Sixth International Arnold Rikli Symposium on the Biologic Effects of Light was held in Boston, Massachusetts from June 16th - 18th, 2001. The goal of this Symposium was to focus on the very popular practice of tanning either by sunlight or by artificial light sources and the overall impact this practice has on health and disease. The program was organized by members of the Scientific Advisory Committee and my co-chair emeritus, Professor Ernst G. Jung. The Program Committee organized an outstanding state-of-the-art program that was enthusiastically received by the participants.

The combination of molecular biology, engineering and bioinformatics has revolutionized our understanding of cancer revealing a tight correlation of the molecular characteristics of the primary tumor in terms of gene expression, structural alterations of the genome, epigenetics and mutations with its propensity to metastasize and to respond to therapy. It is not just one or a few genes, it is the complex alteration of the genome that determines cancer development and progression. Future management of cancer patients will therefore rely on thorough molecular analyses of each single case. Through this book, students, researchers and oncologists will obtain a comprehensive picture of what the first ten years of cancer genomics have revealed. Experts in the field describe, cancer by cancer, the progress made and its implications for diagnosis, prognosis and treatment of cancer. The deep impact on the clinics and the challenge for future translational research become evident.

This book tackles the role of interrelated conditions in the manifestation and course of pulmonary ailments. The articles run the gamut from basic to clinical science on such topics as airway allergy challenges, pulmonary dysfunction due to exposure to environmental pollution, molecular and functional aspects of smoking in lung carcinogenesis and in obstruction-related respiratory disorders, and others. Attention is directed to the developments in rehabilitative and lifestyle interventions in chronic disabilities, particularly involving neuromotor and stress-related conditions which, with advancing age, may lead to the deterioration of ventilation, with hypoxic sequelae. Enhanced research and awareness concerning the lung health drive better treatments and quality of life. Clinical insights presented in the book underscore a major role played by the science in transmuting biomedical knowledge into a better patient management. The volume is addressed to clinicians, researchers, physiotherapists, and other healthcare professionals engaged in effective patient care and therapy.

The Springer Handbook of Auditory Research presents a series of com prehensive and synthetic reviews of the fundamental topics in modern auditory research. It is aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes will introduce new investigators to important aspects of hearing science and will help established inves tigators to better understand the fundamental theories and data in fields of hearing that they may not normally follow closely. Each volume is intended to present a particular topic comprehensively, and each chapter will serve 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 series focusses on topics that have developed a solid data and con ceptual 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."

A grand summary and synthesis of the tremendous amount of data now available in the post genomic era on the structural features, architecture, and evolution of the human genome. The authors demonstrate how such architectural features may be important to both evolution and to explaining the susceptibility to those DNA rearrangements associated with disease. Technologies to assay for such structural variation of the human genome and to model genomic disorders in mice are also presented. Two appendices detail the genomic disorders, providing genomic features at the locus undergoing rearrangement, their clinical features, and frequency of detection.

This book has been written to provide research workers with an introd- tion to several optical techniques for new applications. It is intended to be comprehensible to people from a wide range of backgrounds - no prior optical or physics knowledge has been assumed. However, sufficient technical details have been included to enable the reader to understand the basics of the techniques and to be able to read further from the ref- ences if necessary. The book should be as useful to postgraduate students and experienced researchers as those entering the bioengineering field, irrespective of whether they have a technical or clinical background. It has been prepared with an awareness of the inherent difficulties in und- standing aspects of optics which, in the past, have precluded practical application. The contents address a broad range of optical measurement techniques which have been used in biomechanics, techniques characterized as n- contacting and non-destructive. Theoretical outlines and practical advice on gaining entry to the fields of expertise are complemented by biomec- nical case studies and key literature references. The aim is to present each technique, to appraise its advantages and capabilities and thereby to allow informed selection of an appropriate method for a particular app- cation. It is anticipated that research workers will be assisted in est- lishing new methodologies and gain first-hand experience of the techniques.

This book discusses the application of the concepts of fractals and chaos to biomedical phenomena. In particular, it argues against the outdated notion of homeostasis; using biomedical data sets and modern mathematical concepts, the author attempts to convince the reader that life is at least a homeodynamic process with multiple states - each being capable of survival. Although relying heavily on the new mathematical ideas, the author has attempted to make the book self-contained. The mathematics is developed in a biological context and mathematical formulation for its own sake is avoided. In this book, the phenomena to be explained motivate the mathematical development rather than the other way round.

This book discusses the application of the concepts of fractals and chaos to biomedical phenomena. In particular, it argues against the outdated notion of homeostasis; using biomedical data sets and modern mathematical concepts, the author attempts to convince the reader that life is at least a homeodynamic process with multiple states - each being capable of survival. Although relying heavily on the new mathematical ideas, the author has attempted to make the book self-contained. The mathematics is developed in a biological context and mathematical formulation for its own sake is avoided. In this book, the phenomena to be explained motivate the mathematical development rather than the other way round.

This book summarizes the contributions at an April 2016 conference held at Albany Medical College, Reproductive Ethics: New Challenges and Conversations. Reproductive ethics does not suffer from a lack of challenging issues, yet a few "hot button" issues such as abortion and surrogacy seem to attract most of the attention, while other issues and dilemmas remain relatively underdeveloped in bioethics literature. The goal of this book is to explore and expand the range of topics addressed in reproductive ethics. This is a multi-disciplinary book bringing together philosophers, clinicians, sociologists, anthropologists, and other scholars whose research or clinical interests touch reproductive issues. The results of this compilation are a comprehensive and unique discussion of the evolving issues in the rapidly changing field. The majority of the popular reproductive ethics anthologies were published at least 10 years ago. The field of reproductive ethics would benefit from a new anthology that addresses some of the perennial dilemmas in reproductive ethics (e.g. abortion, sex selection) from updated perspectives and that also covers new technologies that have emerged only in the last few years, such as social egg freezing.

The human brain contains more than a billion neurons which interconnect to form networks that process, store, and recall sensory information. These neuronal activities are supported by a group of accessory brain cells coll- tively known as neuroglia. Surprisingly, glial cells are ten times more - merous than neurons, and occupy more than half the brain volume (Hyden, 1961). Although long considered a passive, albeit necessary, component of the nervous system, many interesting and unusual functional properties of glial cells are only now being brought to light. As a result, the status of these cellular elements is approaching parity with nerve cells as a subject for experimental study. The term glia (or glue) seems today to be a misnomer in view of the diverse functions attributed to glial cells. Experimental studies in the last three decades have clearly established that the behavior of glial cells is far from passive, and that they are at least as complex as neurons with regard to their membrane properties. In addition, glial cells are of importance in signal processing, cellular metabolism, nervous system development, and the pathophysiology of neurological diseases. The Muller cell of the ver- brate retina provides a splendid example of an accessory cell that exhibits features illustrating every aspect of the complex behavior now associated with glial cells.

Investigation of the mechanisms of cellular response to different mechanical stimuli, as well as mechano-electrical feedback (MEF) in the intact heart is one of the main topics in fundamental and clinical cardiology. The present volume of "Mechanosensitivity in Cells and Tissues: Mechanosensitivity of the Heart" c- bines excellent reviews written by worldwide leaders in this ?eld. The 3rd volume is a great addition to this excellent series of books edited by Andre Kamkin and Irina Kiseleva. This volume successfully combines reviews, aimed at academic, physiology and clinical cardiology communities, devoted to mechanosensitivity of the normal and diseased heart at the ion channel, cell, tissue and organ levels. Kamkin and Kiseleva have made signi?cant contributions to the investigation of mechanosentive ion channels in cardiomyocytes and ?broblasts. Their ba- ground, in addition to extensive collaborations helped them to ?nd and consolidate valuable research ?ndings from prominent specialists in the ?eld of cardiac mechanosensitivity. In the last decade, interest in the role of MEF in the heart has increased sign- cantly. MEF within cardiac tissue is a complex phenomenon in which electroph- iological changes are triggered by myocardial stretch. This phenomenon has been studiedintheclinicalcommunityforoveracenturyandmayhavebothpro-rhythmic and arrhythmogenic consequences. While signi?cant advances have been made in understanding of the effects of mechanical forces on cardiac cells, many questions remain regarding the mechanisms whereby mechanical forces are transduced into changes which alter the behavior of various cardiac cells.

This volume is the most recent installment of the Progress in Motor Control series. It contains contributions based on presentations by invited speakers at the Progress in Motor Control IX meeting held in at McGill University, Montreal, in July, 2013. Progress in Motor Control is the official scientific meeting of the International Society of Motor Control (ISMC). The Progress in Motor Control IXI meeting, and consequently this volume, provide a broad perspective on the latest research on motor control in humans and other species."