The Selected Works of C. H. Waddington reissues seven titles from Waddington's impressive oeuvre. The titles in question cover a range of topics, from genetics and embryology to ethics in science and contemporary biological thought.

Featuring a diverse array of model organisms and scientific techniques, Sirtuins: Methods and Protocols collects detailed contributions from experts in the field addressing this vital family of genes. Opening with methods to generate sirtuin biology tools, the book continues by covering methods to identify sirtuin substrates, to measure sirtuin activity, and to study sirtuin biology. 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 easy to use, Sirtuins: Methods and Protocols presents detailed protocols for sirtuin research that can be followed directly or modified to investigate new areas of sirtuin biology.

Microarray technology is a major experimental tool for functional genomic explorations, and will continue to be a major tool throughout this decade and beyond. The recent explosion of this technology threatens to overwhelm the scientific community with massive quantities of data. Because microarray data analysis is an emerging field, very few analytical models currently exist. Methods of Microarray Data Analysis is one of the first books dedicated to this exciting new field. In a single reference, readers can learn about the most up-to-date methods ranging from data normalization, feature selection and discriminative analysis to machine learning techniques. Currently, there are no standard procedures for the design and analysis of microarray experiments. Methods of Microarray Data Analysis focuses on two well-known data sets, using a different method of analysis in each chapter. Real examples expose the strengths and weaknesses of each method for a given situation, aimed at helping readers choose appropriate protocols and utilize them for their own data set. In addition, web links are provided to the programs and tools discussed in several chapters. This book is an excellent reference not only for academic and industrial researchers, but also for core bioinformatics/genomics courses in undergraduate and graduate programs.

By the end of the 1980s only two microtubule-dependent motors, the plus end-directed kinesin and the minus end-directed cytoplasmic dynein, had been identified. At the time, these two motors seemed almost sufficient to explain directional motility events on polar microtubule tracks in the cell. No- theless, shortly after, the tip of the iceberg began to emerge with the identi- cation of proteins containing in their sequences a domain found in kinesin. This domain, called the "motor domain," conferred on these proteins the essential property of moving on microtubules, using the energy derived from ATP hydro- sis. Since then, the identification of new proteins belonging to the kinesin superfamily of microtubule-dependent motors has gone at such a pace that nowadays more than 200 entries with motor domain sequences are deposited in the database. Kinesin family members are found in all eukaryotic org- isms tested. They present a wide range of domain organizations with a motor domain located at different positions in the molecule. Their motility prop- ties are also variable in directionality, velocity, and such other characteristics as bundling activity and processivity. Finally, and most important, they p- ticipate in a multitude of cellular functions. Our understanding of many cel- lar events, such as mitotic spindle assembly and neuronal transport, to cite only two, has progressed substantially in the last few years thanks to the id- tification of these motors.

The second edition of a highly acclaimed handbook and ready reference. Unmatched in its breadth and quality, around 100 specialists from all over the world share their up-to-date expertise and experiences, including hundreds of protocols, complete with explanations, and hitherto unpublished troubleshooting hints. They cover all modern techniques for the handling, analysis and modification of RNAs and their complexes with proteins. Throughout, they bear the practising bench scientist in mind, providing quick and reliable access to a plethora of solutions for practical questions of RNA research, ranging from simple to highly complex. This broad scope allows the treatment of specialized methods side by side with basic biochemical techniques, making the book a real treasure trove for every researcher experimenting with RNA.

The genomes of humans, as well as many other species, are interspersed with hundreds of thousands of tandem repeats of DNA sequences. Those tandem repeats located as codons within open reading frames encode amino acid runs, such as polyglutamine and polyalanine. Tandem repeats have not only been implicated in biological evolution, development and function but also in a large collection of human disorders. In Tandem Repeats in Genes, Proteins, and Disease: Methods and Protocols, expert researchers in the field detail many methods covering the analysis of tandem repeats in DNA, RNA and protein, in healthy and diseased states. This will include molecular genetics, molecular biology, biochemistry, proteomics, biophysics, cell biology, and molecular and cellular approaches to animal models of tandem repeat disorders. Written in the highly successful Methods in Molecular Biology (TM) 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. Authoratative and Practical, Tandem Repeats in Genes, Proteins, and Disease: Methods and Protocols aids scientists in continuing to study the unique methodological challenges that come from repetitive DNA and poly-amino acid sequences.

The development of PCR, which enables extremely small amounts of DNA to be amplified, led to the rapid development of a multiplicity of a- lytical procedures to utilize this new resource for analysis of genetic variation and for the detection of disease causing mutations. The advent of capillary electrophoresis (CE), with its power to separate and analyze very small amounts of DNA, has also stimulated researchers to develop analytical procedures for the CE format. The advantages of CE in terms of speed and reproducibility of analysis are manifold. Further, the high sensitivity of detection, and the ab- ity to increase sample throughput with parallel analysis, has led to the creation of a full range of analysis of DNA molecules, from modified DNA-adducts and single-strand oligonucleotides through to PCR-amplified DNA fragments and whole chromosomes. Capillary Electrophoresis of Nucleic Acids focuses on such analytical protocols, which can be used for detection and analysis of mutations and modification, from precise DNA loci through to entire genomes of organisms. Important practical considerations for CE, such as the choice of separation media, electrophoresis conditions, and the influence of buffer additives and dyes on DNA mobility, are discussed in several key chapters and within particular applications.

With the dramatic increase in RNA 3D structure determination in recent years, we now know that RNA molecules are highly structured. Moreover, knowledge of RNA 3D structures has proven crucial for understanding in atomic detail how they carry out their biological functions. Because of the huge number of potentially important RNA molecules in biology, many more than can be studied experimentally, we need theoretical approaches for predicting 3D structures on the basis of sequences alone. This volume provides a comprehensive overview of current progress in the field by leading practitioners employing a variety of methods to model RNA 3D structures by homology, by fragment assembly, and by de novo energy and knowledge-based approaches.

Genetic erosions in plant cell cultures, especially in chromosome number and ploidy level, have now been known for over 25 years. Until the mid -1970ssuch changes were consideredundesirable and thereforediscarded because the main emphasis wason clonal propagation and genetic stability of cultures. However, since the publication on somaclonal variation by Larkin and Scowcroft (1981) there has been a renewed interest to utilize these in vitro obtained variations for crop improvement. Studies conduc- ted during the last decade have shown that callus cultures, especially on peridical subculturing over an extended period of time, undergo morpho- logical and genetic changes, i. e. polyploidy, aneuploidy, chromosome breakage, deletions, translocations, gene amplification, inversions, muta- tions, etc. In addition, there are changes at the molecular and biochemical levelsincluding changes in the DNA, enzymes,proteins, etc. Suchchanges are now intentionally induced, and useful variants are selected. For instance in agricultural crops such as potato, tomato, tobacco, maize, rice and sugarcane, plants showing tolerance to a number of diseases, viruses, herbicides and salinity, have been isolated in cell cultures. Likewise induction of male sterility in rice, and wheat showing various levels of fer- tility and gliadin, have been developed in vitro. These academic excercises open new avenues for plant breeders and pathologists. Another area of tremendous commercial importance in the pharmaceuti- cal industry is the selection of cell lines showing high levels of medicinal and industrial compounds. Already high shikonin containing somaclones in Lithospermum are being used commercially.

This book addresses the development of both DNA-sequence-selective and DNA-form-selective ligands, with the aim of creating potential molecular probes and therapeutic agents for non-canonical DNA structure-caused human diseases. Over the past two decades, the structural diversity of DNA forms has been proven to have profound implications in various biological, neurological, and pharmacological events. In response, researchers have since made tremendous efforts to obtain highly active drugs interacting with disease-related non-canonical DNA structures. These drugs, however, have not yet been approved for clinical use. One obstacle impeding their clinical application has to do with selectivity. This book focuses on secondary DNA structures formed by trinucleotide repeat sequences ("hairpin form") or guanine-rich sequences ("G-quadruplex form"), both of which are pathological molecules for neurodegenerative diseases and/or cancer. Most importantly, it contends that a particular secondary structure of DNA in the context of the human genome can be targeted with a minimal affinity to other DNA structures by means ofcareful and rational ligand design. This approach opens an avenue to the development of highly selective drugs or diagnostic chemical tools for human diseases. Readers who want to know how synthetic ligands can be designed to selectively target a certain DNA molecule will find this book highly informative.

Developmental Instability: Its Origins and Evolutionary Implications is a collection of papers and transcribed discussions from a conference held in Tempe, Arizona in June 1993. The papers represent a wide range of contributions, from the empirical to the theoretical, and include methods for measuring developmental instability across a variety of taxa and traits. This volume presents contrasting views on how to assess developmental instability as well as on the relationship of instability to genotypic factors, environmental factors and the action of natural and sexual selection. Readers will derive a working knowledge of the best way to assess developmental instability and will be able to design future work in an authoritative way.

These are indeed exciting times to be a microbiologist. With one of the buzzwords of the past decade-"Biodiversity," and microbes are reveling in the attention as they represent by far most of the biodiversity on Earth. Microbes can thrive in almost any environment where there is an exploitable energy source, and, as a result, the possible existence of microbial life elsewhere in the solar system has stimulated the imaginations of many. Extremophiles have taken center stage in these investigations, and thermophiles have taken on the lead roles. Consequently, in the past decade there has been a surge of interest and research in the Ecology, Biology, and Biotechnology of microorganisms from thermal environments. Many of the foundations of thermophile research were laid in Yellowstone National Park, primarily by the research of Professor Thomas Brock's laboratory in the late 1960s and early 1970s. The upper temperature for life was debated, the first thermophilic archeum discovered (although it was only later shown to be an archeum by ribosomal cataloging), and the extremes of light, temperature, pH on the physiology of microorga nisms were explored. Interest in thermophiles increased steadily in the 1970s, and with the discovery of deep-sea hydrothermal vents in 1977, thermophilic research began its expo nential explosion. The development of Taq polymerase in the polymerase chain reaction (peR) focused interest on the biotechnological potential of thermophilic microorganisms and on the thermal features in Yellowstone National Park."

This book aims at defining and reassessing the role of population genetics in conservation biology and seeks to identify the progress made in the field during the last decade. It deals with conservation genetics from several currently researched points of view, namely, ecological and demographic measures of rarity or population persistence, loss of genetic variation, inbreeding, reduced migration rates and increased selective pressures under stress and the role of social behaviour and metapopulation structure. The use of molecular variation as the basis of naming or selecting target taxa and some strategic decisions about genetic variance maximization in the conserved population or community units are analysed. Several case studies and scenarios illustrate the application of genetic information in conservation practices.

Cardiac Gene Expression: Methods and Protocols presents both cutting-edge and established methods for studying cardiac gene expression. The protocols provide a template for solid research, and cover the process through screening, analysis, characterization, and functional confirmation of novel genes or known genes with a new function.
Section I, Cardiac Gene Expression Profiling: The Global Perspective, discusses several different approaches to examining, identifying, and analyzing changes in transcriptome gene expression. Section II, Cardiac Gene Regulation: Gene-Specific mRNA Measurement in the Myocardium, outlines more sensitive and gene-targeted expression methods. Section III, Cardiac Gene Regulation: Promoter Characterization in the Myocardium, provides protocols for the study of underlying gene regulation mechanisms by focusing on the interaction of transcription factors with their cognate cis binding elements. Section IV, In Silico Assessment of Regulatory cis-Elements and Gene Regulation, and Section V, Cardiac Single Network Polymorphisms, emphasize new analytical approaches for deciphering the functional elements buried in the 3 billion nucleotides of the human genome and other model genomes. The concluding section, Gene Overexpression and Targeting in the Myocardium, highlights methods that facilitate overexpression or cardiac-specific targeted gene deletion.

Aging of somatic stem cells reduces cell function and results in dysfunctional organs and tissues, making it an underlying cause of diseases associated with aging. It might even be the primary cause for age-associated attrition of tissue function in organs that heavily rely on stem cells for maintaining homeostasis, like the skin, blood and intestines. Understanding the molecular and cellular mechanisms involved is critical for developing approaches to attenuate stem cell aging and could pave the way for improved quality of life among the elderly. Written by highly prominent experts in the field, this book presents the current state of knowledge on these mechanisms. It offers insights into stem cell function, explains in detail the mechanisms of stem cell aging in model organisms as well as mammalian systems and describes related diseases and approaches to attenuating stem cell aging or achieving rejuvenation. The book is intended for all scientists and clinicians working with stem cells, aging mechanisms or age-related diseases.

This book covers the identification and role of endogenous lung stem cells in health and disease, particularly the most recent advances. In addition, it discusses the rapidly growing field of stem cells and cell therapy as it relates to lung biology and disease as well as ex vivo lung bioengineering. Such approaches may provide novel therapeutic approaches for lung diseases. Human pluripotent stem cell differentiation to model the pulmonary epithelium and vasculature is also discussed. World-recognized scientists who specialize in studying both the lung epithelium and pulmonary vasculature contribute the chapters. Topics covered include: stem cell niches in the lung, the role of progenitor cells in fibrosis and asthma, iPSC in modeling lung disease, vascular repair by endothelial progenitor cells and circulating fibrocytes in pulmonary vascular remodeling. This volume of the Stem Cell Biology and Regenerative Medicine series is essential reading for researchers and clinicians interested in stem cells, lung biology and regenerative medicine. It is also an invaluable resource for advanced students studying cell biology, regenerative medicine and lung physiology.

Bioinformatics is an integrative field of computer science, genetics, genomics, proteomics, and statistics, which has undoubtedly revolutionized the study of biology and medicine in past decades. It mainly assists in modeling, predicting and interpreting large multidimensional biological data by utilizing advanced computational methods. Despite its enormous potential, bioinformatics is not widely integrated into the academic curriculum as most life science students and researchers are still not equipped with the necessary knowledge to take advantage of this powerful tool. Hence, the primary purpose of our book is to supplement this unmet need by providing an easily accessible platform for students and researchers starting their career in life sciences. This book aims to avoid sophisticated computational algorithms and programming. Instead, it will mostly focus on simple DIY analysis and interpretation of biological data with personal computers. Our belief is that once the beginners acquire these basic skillsets, they will be able to handle most of the bioinformatics tools for their research work and to better understand their experimental outcomes. The third volume is titled In Silico Life Sciences: Agriculture. It focuses on plant genetic, genomic, transcriptomic, proteomic and metabolomics data. Using examples of new crop diseases-emergence, crop productivity and biotic/abiotic stress tolerance, this book illustrates how bioinformatics can be an integral components of modern day plant science research.

Leishmania is a vector-borne pathogenic parasite found in 88 countries worldwide and is the causative agent of leishmaniasis. The different Leishmania species infect macrophages and dendritic cells of the host immune system, causing symptoms that range from disfiguring cutaneous and mucocutaneous lesions, widespread destruction of mucous membranes, or visceral disease affecting the haemopoetic organs. The recent publication of the complete genome sequences of three different Leishmania species provides new insights into this leading pathogen and presents scientists with an exciting resource to improve the understanding of its complex molecular and cellular biology. In this book, internationally recognized Leishmania experts critically review the most important aspects of current Leishmania research, providing the first coherent picture of the organism's molecular and cellular biology since the publication of the genome sequence. Chapters are written from a molecular and genomic perspective and discuss in depth Leishmania-specific aspects of trypanosomatid biology and pathology. Topics include: diagnosis and epidemiology, genome structure and content, regulation of gene expression, the Leishmania proteome, the Leishmania metabolome, Leishmania differentiation, interaction with the sand fly vector, drug discovery, drug resistance, and much more. This will be essential reading for all researchers working with Leishmania, trypanosomes, and protozoa; and is recommended for all biology and medical libraries.

This volume explores the applications of reporter gene technology and the methodologies needed for their effective implementation. The chapters in this book cover practical topics such as how to integrate reporter constructs into cellular models, viral delivery, splicing applications, in vivo imaging, and a guide to the use of multi-cistronic constructs. Additionally, chapters also include detailed mechanistic uses of reporter genes in cellular pathways, and a look at project and data management of screening applications. 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. Cutting-edge and thorough, Reporter Gene Assays: Methods and Protocols is a valuable resource for anyone who is interested in learning more about reporter genes.

This book contains a broad survey on the peroxiredoxins. It involves almost all groups that contributed significant insights into the emerging field. Coverage discusses the diverse biological roles of the new protein family in the context of other antioxidant systems like those based on heme or selenium catalysis. In addition, the book highlights related future perspectives.

Discusses the problem of structural-functional organization of eukaryotic cell nuclei with special emphasis on the genome spatial organization and functioning. The opening chapters describe the nuclear matrix and the fate of its components in the course of mitosis. In the next eight chapters the organization of chromosomal DNA into large loops and

In the past several years, DNA microarray technology has attracted tremendous interest in both the scientific community and in industry. With its ability to simultaneously measure the activity and interactions of thousands of genes, this modern technology promises unprecedented new insights into mechanisms of living systems. Currently, the primary applications of microarrays include gene discovery, disease diagnosis and prognosis, drug discovery (pharmacogenomics), and toxicological research (toxicogenomics). Typical scientific tasks addressed by microarray experiments include the identification of coexpressed genes, discovery of sample or gene groups with similar expression patterns, identification of genes whose expression patterns are highly differentiating with respect to a set of discerned biological entities (e.g., tumor types), and the study of gene activity patterns under various stress conditions (e.g., chemical treatment). More recently, the discovery, modeling, and simulation of regulatory gene networks, and the mapping of expression data to metabolic pathways and chromosome locations have been added to the list of scientific tasks that are being tackled by microarray technology. Each scientific task corresponds to one or more so-called data analysis tasks. Different types of scientific questions require different sets of data analytical techniques. Broadly speaking, there are two classes of elementary data analysis tasks, predictive modeling and pattern-detection. Predictive modeling tasks are concerned with learning a classification or estimation function, whereas pattern-detection methods screen the available data for interesting, previously unknown regularities or relationships.

This book uses the reaction of a number of biologists in the United States and Great Britain to provide an overview of one of the most important controversies in Twentieth Century biology, the "Lysenko Affair." The book is written for advanced undergraduate and graduate students of history/history of science. It covers a number of topics which are relevant to understanding the sources and dimensions of the Lysenko controversy, including the interwar eugenics movement, the Scopes Trial, the popularity of Lamarckism as a theory of heredity prior to the synthesis of genetics and Natural Selection, and the Cold War. The book focuses particularly on portrayals-both positive and negative-of Lysenko in the popular press in the U.S. and Europe, and thus by extension the relationship between scientists and society. Because the Lysenko controversy attracted a high level of interest among the lay community, it constitutes a useful historical example to consider in context with current topics that have received a similar level of attention, such as Intelligent Design or Climate Change.

In the preface to Sir Vincent B. Wigglesworth's classic 1939 book on insect physiology he asserted that insects provide an ideal medium in which to study all the problems of physiology. A strong case can be made as well for the use of insects as significant systems for the study of behavior and genetics. Contributions to genetics through decades of research on Drosophila species have made this small fly the most important metazoan in genetics research. At the same time, population and behavioral research on insects and other invertebrates have provid ed new perspectives that can be combined with the genetics approach. Through such in tegrated research we are able to identify evolutionary genetics of behavior as a highly signifi cant emerging area of interest. These perspectives are ably described by Dr. Guy Bush in the introductory chapter of this book. During March 21-24, 1983, many of the world's leading scientists in invertebrate behavioral genetics were drawn together in Gainesville, Florida, for a colloquium entitled "Evolutionary Genetics of Invertebrate Behavior." This conference was sponsored jointly by the Department of Entomology and Nematology, University of Florida, chaired by Dr. Daniel Shankland, and the Insect Attractants, Behavior and Basic Biology Research Laboratory, U.S. Department of Agriculture, directed then by Dr. Derrell Chambers."