Amino acid analysis is a technique that has become commonplace in biotechnology, biomedical, and food analysis laboratories. This book describes a variety of amino acid analysis techniques and how each technique can be used to answer specific biological questions. The first two chapters in Amino Acid Analysis Protocols introduce the concepts, basic theory, and practice of amino acid analysis. The following chapters give detailed instructions on various methods and their applications. As highlighted, there are many different approaches to amino acid ana- sis, but in all cases the results depend heavily on the quality of the sample. Therefore a new way to desalt samples prior to hydrolysis is covered as an introductory chapter (Chapter 3), and most authors have devoted a section to sample preparation, especially to the collection and storage of bodily fluids. Some of the amino acid analysis methods described in this book are based on HPLC separation and analysis after precolumn derivatization. The precolumn derivatization techniques described use (a) 6-aminoquinolyl-N-hydro- succinimidyl carbamate (AQC) (Chapters 4 and 8); (b) 1-fluoro-2- dinitrophenyl-5-L-alanine amide (Marfey's reagent), which allows sepa- tion and analysis of enantiomeric amino acids (Chapter 5); (c) O-phthalal- hyde (OPA) (Chapters 6 and 10); (d) butylisothiocyanate (BITC) and benzylisothiocyante (BZITC) (Chapter 11); (e) phenylisothiocyanate (PITC) (Chapters 12 and 13); (f) ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-s- fonate (SBD-F) (Chapter 17); and (g) 9-fluorenylmethyl-chloroformate (FMOC-Cl) (Chapter 10).

Distinguished physicians critically review the clinical consequences of the endocrinological changes that occur with aging-in both men and women-and examine the use of hormonal therapy to reduce them. Topics range from bone disease and water balance in all older people, to androgen deficiency in aging males, gynecomastia, and menopause. The authors also discuss Type II diabetes in persons over 65, emphasizing the cognitive benefits of good glycemia control, and the interaction of nutrition and metabolism, focusing on hypocholesterolemia, obesity, the anorexia of aging, trace elements, and vitamins. The aging of the sympathetic nervous system and its impact on hypertension in the elderly is also covered. Timely and authoritative, Endocrinology of Aging offers endocrinologists, geriatricians, and primary care physicians critical insight into the endocrine problems of our rapidly growing elderly population.

Systems Metabolic Engineering is changing the way microbial cell factories are designed and optimized for industrial production.
Integrating systems biology and biotechnology with new concepts from synthetic biology enables the global analysis and engineering of microorganisms and bioprocesses at super efficiency and versatility otherwise not accessible. Without doubt, systems metabolic engineering is a major driver towards bio-based production of chemicals, materials and fuels from renewables and thus one of the core technologies of global green growth. In this book, Christoph Wittmann and Sang-Yup Lee have assembled the world leaders on systems metabolic engineering and cover the full story from genomes and networks via discovery and design to industrial implementation practises.
This book is a comprehensive resource for students and researchers from academia and industry interested in systems metabolic engineering. It provides us with the fundaments to targeted engineering of microbial cells for sustainable bio-production and stimulates those who are interested to enter this exiting research field.

This volume presents detailed laboratory protocols for in vitro synthesis of mRNA with favorable properties, its introduction into cells by a variety of techniques, and the measurement of physiological and clinical consequences such as protein replacement and cancer immunotherapy. Synthetic techniques are described for structural features in mRNA that provide investigational tools such as fluorescence emission, click chemistry, photo-chemical crosslinking, and that produce mRNA with increased stability in the cell, increased translational efficiency, and reduced activation of the innate immune response. Protocols are described for clinical applications such as large-scale transfection of dendritic cells, production of GMP-grade mRNA, redirecting T cell specificity, and use of molecular adjuvants for RNA vaccines. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Synthetic mRNA: Production, Introduction into Cells, and Physiological Consequences is a valuable and cutting-edge resource for both laboratory investigators and clinicians interested in this powerful and rapidly evolving technology.

Carl Edward Sagan's (1934-1996) one of the famous quotation was "Who are we? We find that we live on an insignificant planet of a humdrum star lost in a galaxy tucked away in some forgotten corner of a universe in which there are far more galaxies than people." From past to date, well-known molecules, enzymes, proteins, lipids and carbohydrates are studied in the pathogenesis of several diseases both as a diagnostic/prognostic biomarker and therapeutic agent. The underlying mechanism of unexplained diseases and failure of therapies are frequently studied with well-known biomarkers, but remain unclear in many cases. As Dr. Sagan said other keys are still waiting to be known in some forgotten corner of a body universe, we find strength to propose that one of them can be the growth factor with cytokine activity named "Midkine" This book summarizes the extensive up-to-date literature overeview with the lastest work of experts about midkine in a detailed format that conveys its role as both a pathologic factor and therapeutic agent.

Recent studies have indicated that epigenetic processes may play a major role in both cellular and organismal aging. These epigenetic processes include not only DNA methylation and histone modifications, but also extend to many other epigenetic mediators such as the polycomb group proteins, chromosomal position effects, and noncoding RNA. The topics of this book range from fundamental changes in DNA methylation in aging to the most recent research on intervention into epigenetic modifications to modulate the aging process. The major topics of epigenetics and aging covered in this book are: 1) DNA methylation and histone modifications in aging; 2) Other epigenetic processes and aging; 3) Impact of epigenetics on aging; 4) Epigenetics of age-related diseases; 5) Epigenetic interventions and aging: and 6) Future directions in epigenetic aging research.

The most studied of epigenetic processes, DNA methylation, has been associated with cellular aging and aging of organisms for many years. It is now apparent that both global and gene-specific alterations occur not only in DNA methylation during aging, but also in several histone alterations. Many epigenetic alterations can have an impact on aging processes such as stem cell aging, control of telomerase, modifications of telomeres, and epigenetic drift can impact the aging process as evident in the recent studies of aging monozygotic twins.

Numerous age-related diseases are affected by epigenetic mechanisms. For example, recent studies have shown that DNA methylation is altered in Alzheimer s disease and autoimmunity. Other prevalent diseases that have been associated with age-related epigenetic changes include cancer and diabetes. Paternal age and epigenetic changes appear to have an effect on schizophrenia and epigenetic silencing has been associated with several of the progeroid syndromes of premature aging. Moreover, the impact of dietary or drug intervention into epigenetic processes as they affect normal aging or age-related diseases is becoming increasingly feasible.

This book covers the statistical models and methods that are used to understand human genetics, following the historical and recent developments of human genetics. Starting with Mendel's first experiments to genome-wide association studies, the book describes how genetic information can be incorporated into statistical models to discover disease genes. All commonly used approaches in statistical genetics (e.g. aggregation analysis, segregation, linkage analysis, etc), are used, but the focus of the book is modern approaches to association analysis. Numerous examples illustrate key points throughout the text, both of Mendelian and complex genetic disorders. The intended audience is statisticians, biostatisticians, epidemiologists and quantitatively- oriented geneticists and health scientists wanting to learn about statistical methods for genetic analysis, whether to better analyze genetic data, or to pursue research in methodology. A background in intermediate level statistical methods is required. The authors include few mathematical derivations, and the exercises provide problems for students with a broad range of skill levels. No background in genetics is assumed.

For scientists, no event better represents the contest between form and function as the chief organizing principle of life as the debate between Georges Cuvier and Etienne Geoffroy Saint-Hilaire. This book presents the first comprehensive study of the celebrated French scientific controversy that focused the attention of naturalists in the first decades of the nineteenth century on the conflicting claims of teleology, morphology, and evolution, which ultimately contributed to the making of Darwin's theory. This history describes not only the scientific dimensions of the controversy and its impact on individuals and institutions, but also examines the meaning of the debate for culture and society in the years before Darwin.

This book, together with the next two volumes to follow, offers the scientific community the works and thoughts of Santiago Ram n y Cajal. The text is a faithful rendition of the original Spanish version, with additional facts taken from the French translation. Both of these are currently quoted an average of 200 times a year in the scientific literature. This collection will represent the "definitive Cajal" for scientists and scholars interested in the original thoughts of probably the most prominent neuroscientist of all time.

Mitosis: Methods and Protocols provides state-of-the-art overviews on the most important approaches currently used in mitosis research spanning from the analysis of single molecules in isolation to their utilization within the complex environment of the cell. The volume is divided into four parts, each focused on methods pertaining to distinct aspects of mitosis research. Part I presents approaches for visualizing and analyzing the dynamic behaviors of the spindle apparatus, the microtubule based machine that drives chromosome segregation. Part II focuses more generally on methods for studying and manipulating the microtubule cytoskeleton in cells and complex cell free extracts. Part III provides state of the art biophysical and high resolution microscopy approaches for assessing complex interactions between microtubules and microtubule-associated proteins in isolation as well as microtubule structure in cells. Part IV provides methods for studying the effects of cell shape on cell division and methods for quantifying aneuploidy (aberrant chromosome number) which frequently results from mitotic defects and has been linked to human maladies ranging from birth defects to cancer. Written in the highly 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 laboratory protocols and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Mitosis: Methods and Protocols seeks to provide diverse methods and new techniques to address new or old questions related to the mechanisms of mitosis.

aintaining extracellular calcium concentrations within a narrow range is critical for the survival of most vertebrates. PTH, together with vitamin D, responds to hypocalcemia to increase extracellu M lar calcium levels, by acting on bone, kidney and intestine. The recent intro duction of PTH as a major therapeutic agent in osteoporosis has directed renewed interest in this important hormone and in the physiology of the parathyroid gland. The parathyroid is unique in that low serum calcium stimulates PTH secretion. As hypocalcemia persists, there is also an increase in PTH synthesis. Chronic hypocalcemia leads to hypertrophy and hyper plasia of the parathyroid gland together with increased production of the hormone. Phosphate is also a key modulator of PTH secretion, gene expres sion and parathyroid cell proliferation. Understanding the biology of the parathyroid as well as the mecha nisms of associated diseases has taken great strides in recent years. This book summarizes the molecular mechanisms involved in the function of the para thyroid gland. The first chapter reviews the development of the parathyroid gland and the genes involved in this process as identified using genetically manipulated mice. Then the biosynthetic pathway of PTH from gene ex pression to its intracellular processing and the sequences in the gene control ling its transcription as well as those regulating mRNA processing, stability and translation are described.

This volume includes comprehensive descriptions of miRNA biogenesis and their role in the development and progression of various human diseases. The first few chapters of MicroRNA Profiling: Methods and Protocols discuss the effects of over-expressing and repressing of a target miRNA and their effects on cell viability and proliferation. The next few chapters explore the protocols for total RNA isolation from cells and cell-derived product including formalin fixed paraffin embedded tissue and plant tissue. The last few chapters discuss isolation and characterization of exosomes from medium conditioned by cell lines, serum, and plasma specimens. This book also includes discussions of several software tools, such as miRandola, PicTar, DIANA, and miRWalk. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, MicroRNA Profiling: Methods and Protocols is a valuable resource for anyone interested in the field of Micro RNAs.

The metabolic syndrome is a common syndrome affecting about 20 % of the adult population in Europe, and probably the prevalence is of the same magnitude in other industrialised countries worldwide. It is mainly caused by western lifestyle resulting in abdominal obesity, but also a genetic predisposition plays a role. This syndrome, which is linked to leisure lifestyle and overeating/obesity, can develop into type 2 diabetes, cardiovascular disease and cancer. Therefore, proper treatment and prevention are heavily needed. This book discusses lifestyle intervention and treatment, specifically with pharmacological compounds, in order to formulate a strategy for treating the metabolic syndrome in the daily clinic.

Defining and understanding cellular and molecular mechanisms that are relevant to women's health has become a critical area of scientific pursuit. Until recently, very little effort has been place on defining or understanding critical differences between women and men that may be critical to the overall health of the woman. In 1990, the National Institutes of Health recognized this gap in knowledge resulting in the creation of the Office of Research on Women's Health. One of the purposes of this office was to advance the understanding of health issues from the women's perspective from both a basic and clinical scientific perspective. From a scientific evolution of understanding, the existence of this office is new and thus there has not been enough time for new information to integrate itself in our current scientific thought process. This book will seek to capture and disseminate our current understanding of scientific advancements relevant to women's health and provide the information to a broad audience. The purpose of this work is to discuss recent advancements in basic science across three areas of concern for women's health. In addition, the book will provide "translational" chapters that attempt to place the basic science work in context within our current understanding of the human. Although it is well acknowledge that gender differences exist across organ function which translates into differences in whole body function, until recently little effort has been made to define basic mechanisms within various tissues within the woman. This work will focus on recent scientific findings that are relevant to women's health and to provide novel and relevant information to interested scientists and clinicians.

In dealing with recent advances in biological engineering and human reproduction, we are confronted with legal, ethical, and religious questions for which there are no precedents. Warren Freedman undertakes a comprehensive examination of this topic. Sorting through the tangle of issues surrounding artificial insemination, surrogate motherhood, and other aspects of contemporary reproduction trends, Freedman attempts to clarify the rights and responsibilities of individuals, families, and society in the face of these new developments.

The author begins with a survey of the legal implications of nontraditional approaches to conception and birth. Separate chapters are devoted to artificial insemination and surrogate motherhood; and new concepts such as cryo-preservation, in-vitro fertilization, banking of sperms and eggs, and patentable new organisms are also discussed in detail. The author addresses questions of rights and liabilities as they apply to fetuses, donors, and adoptive parents, as well as the role of physicians and parenthood organizations, researchers, corporations, and government. Following a review of existing statutes, policies, and contracts that attempt to deal with these issues both here and abroad, he presents proposals that may aid in achieving equitable, uniform solutions. Freedman's book will be of interest to any citizen, group, or government agency concerned with these vital questions, and to professionals in law, government, medicine, human services, and industry.

Teratology is the study of chemical-induced birth defects. This book is a comprehensive guide to the procedures and methods commonly employed in the safety testing of all classes of chemical for teratogenicity (also referred to as embryotoxicity, developmental toxicity or prenatal toxicity). The various international regulatory requirements are explained in detail, in order that the reader may perform all of the necessary studies for the successful registration or marketing authorisation of a new pharmaceutical, industrial chemical, crop protection product or food additive. Written in the highly successful Methods in Molecular Biology (TM) series format, each chapter gives clear complete instructions on how to perform the task in hand. The authors are respected experts in their field, all with hands-on experience of the procedures described. Teratogenicity Testing: Methods and Protocols gives crucial guidance and tips on how to deal with unexpected results and overcome regulatory difficulties.

Epigenetic modifications underlie all aspects of human physiology, including stem cell renewal, formation of cell types and tissues. They also underlie environmental impacts on human health, including aging and diseases like cancer. Consequently, cracking the epigenetic "code" is considered a key challenge in biomedical research. Chromatin structure and function are modified by protein complexes, causing genes to be turned "on" or "off" and controlling other aspects of DNA function. Yet while there has been explosive growth in the epigenetics field, human chromatin-modifying machines have only recently started to be characterized. To meet this challenge, our book explores complementary experimental tracks, pursued by expert international research groups, aimed at the physical and functional characterization of the diverse repertoire of chromatin protein machines - namely, the "readers, writers and erasers" of epigenomic marks. These studies include the identification of RNA molecules and drugs that interact selectively with components of the chromatin machinery. What makes this book distinctive is its emphasis on the systematic exploration of chromatin protein complexes in the context of human development and disease networks.

This volume provides insight into recent developments on experimental and clinical strategies for cancer gene therapy. Gene Therapy of Solid Cancers: Methods and Protocols guides readers through protocols on gene therapeutic strategies in combination with helpful technical notes. Written in the highly 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 laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Gene Therapy of Solid Cancers: Methods and Protocols aims to ensure successful results in the further study of this vital field.

First published in 1985, the revised edition of this text consists of seven chapters describing the muscle, its anatomy, its mechanics, and its chemical and neuro-control systems. It documents empirical, analytical, and experimental analyses and equations in the field of muscle mechanics.

The editor of this volume takes on the challenging task of presenting an encompassing view of childbirth in America from an anthropological perspective. The book is indeed comprehensive. . . . Collectively the chapters in Childbirth in America lay out a representative sketch of research problems of interest to sociocultural anthropologists and other social scientists working in the area of reproductive health. A distinct accomplishment is the acknowledgement in some of the chapters that not all American women want the same kind of childbirth care or have the same values and attitudes about pregnancy, birth, and parenting, and that this variation needs addressing in both childbirth policy and practice. American Journal of Physical Anthropology A comprehensive and critical examination of the experience of childbirth in America today, from pregnancy to early postpartum. This book covers many controversial issues in the context of diverse cultural, social, and economic backgrounds, which have arisen as a result of the new technologies and ideologies surrounding pregnancy and birth. Most useful as a text for courses in childbirth education, anthropology of women's health, and anthropology of medicine.

This volume of the Handbook of Neurochemistry and Molecular Biology focuses on molecular events involved in synapse formation, synaptic plasticity and ongoing neural activity. The volume explores axonal growth cones, synapse development, and mechanisms of LTP and LTD, and calcium dynamics. Particular attention is given to function and trafficking of membrane proteins including various ion channels, aquaporines, gap junctions.

Since Paul Cranefield published his monograph, The Conduction of the Cardiac Impulse, in 1975, much has been learned about the role of the slow inward current in cardiac electrophysiology. Because of this expanse in know ledge, both basic and clinical, it appeared reasonable to review in a mono graph once again what was known. When Martinus Nijhoff first approached us to undertake the task of updating this information, we were initially reluctant for several reasons. First, we did not feel that the subject could be adequately and thoroughly reviewed, from the cell to the bedside, by a single person. Second, time constraints on all of us precluded even attempting such a task. However, we were encouraged by several of our friends (' egged on' one might even say, since they wished the job done but did not want to do it themselves ) who promised faithfully to contribute chapters on time if we accepted the task. So we did, and most of them did also."