All physicians practicing medicine encounter patients suffering from cardiovascular disease. This book has been outlined in such a way that vascular surgeons, general internists, neurologists and cardiologists should be able to use it. The book covers the complete scope of cardiac diseases in addition to chapters on hypertension and atherosclerosis. In many patients there is a family history of cerebrovascular accidents, myocardial infarction or peripheral arterial disease. Also in patients reporting collaps, palpitations and arrhythmias the family is crucial and can provide clues to a genetic cause of the disease. This book is published to guide physicians in the process of determining whether a genetic component is likely to be present. Furthermore, information is provided what the possibilities and limitations of DNA diagnostic techniques are. Finally, the importance of newly identified categories of potential patients, i. e. gene carriers without symptoms or any inducible sign of disease, is highlighted. For some patients a genetic diagnosis is essential to determine appropriate therapy and for counseling? In some other diseases DNA diagnostic tools are available but the relevant for the patients may be less clear. In other families the search for a disease causing gene is ongoing and the possibilities to find genes and to unravel the pathophysiology of the disease is limited by the lack of patients. To give insight into the current state of genetic diagnostics, the authors have classified the cardiovascular diseases.

RNA technologies are the driving forces of modern medicine and biotechnology. They combine the fields of biochemistry, chemistry, molecular biology, cell biology, physics, nanotechnology and bioinformatics. The combination of these topics is set to revolutionize the medicine of tomorrow. After more than 15 years of extensive research in the field of RNA technologies, the first therapeutics are ready to reach the first patients. Thus we are witnessing the birth of a very exciting time in the development of molecular medicine, which will be based on the methods of RNA technologies. This volume is the first of a series. It covers various aspects of RNA interference and microRNAs, although antisense RNA applications, hammerhead ribozyme structure and function as well as non-coding RNAs are also discussed. The authors are internationally highly respected experts in the field of RNA technologies.

The integrin family is composed of 24 members and approximately ten years ago (2003) we published a book devoted to the nine I domain integrin subunits. In this second edition, I am pleased that most of the original authors have been able to contribute to the updated version.

I domain containing integrins include collagen receptors and leukocyte receptors. In 2003 the knockout mouse phenotypes for all of the I domain integrins had not yet been published; they are now, and are summarized and discussed in this edition.

Interestingly, a recent 10 integrin mutation in dogs has indicated that collagen-binding integrins in the musculoskeletal system might have much more severe phenotypes in larger animals/humans compared to the mild integrin phenotypes observed in collagen-binding integrin deficient mice. This finding is further discussed in the book.

In the cancer field, the microenvironment is taking center stage, and here collagen receptors on fibroblasts are predicted to play important roles in paracrine signaling, in regulating tissue stiffness and matrix remodeling.

New technologies, new mouse models in combination with analyses of I integrins in larger animals/humans are thus predicted to increase our knowledge about this group of receptors. With this in mind we look forward to another 10 years of research with I domain integrins.

Data Mining and Applications in Genomics contains the data mining algorithms and their applications in genomics, with frontier case studies based on the recent and current works at the University of Hong Kong and the Oxford University Computing Laboratory, University of Oxford. It provides a systematic introduction to the use of data mining algorithms as an investigative tool for applications in genomics. Data Mining and Applications in Genomics offers state of the art of tremendous advances in data mining algorithms and applications in genomics and also serves as an excellent reference work for researchers and graduate students working on data mining algorithms and applications in genomics.

Structural Genomics and Drug Discovery: Methods and Protocols focuses on high throughput structure determination methods and how they can be applied to lay the groundwork for structure aided drug discovery. The methods and protocols that are described can be applied in any laboratory interested in using detailed structural information to advance the initial stages of drug discovery. 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, Structural Genomics and Drug Discovery: Methods and Protocols seeks to aid scientists in the further study into structural genomics approach as an efficient initial step toward drug discovery and the methods described will be useful to anyone interested in moving in this direction.

The aim of the book is to discuss the application of molecular pathology in cancer research, and its contribution in the classification of different tumors and identification of potential molecular targets, as well as how this knowledge may be translated into clinical practice, and the huge impact this field is likely to have in the next 5 to 10 years.

The numerous vital applications of complementary DNA (cDNA) technology have changed dramatically as the technology has advanced over recent years. In cDNA Libraries: Methods and Protocols, expert researchers provide current techniques that reflect the latest advances in the construction and application of cDNA libraries. The first half of the volume covers improved approaches to some of the most basic elements of creating cDNA libraries, while the second half casts a much wider net and includes visionary applications of cDNA technology which were either unforeseen or technically impractical until recently. 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. Authoritative and cutting-edge, cDNA Libraries: Methods and Protocols serves as an ideal guide to all scientists seeking to advance this important technology and provide answers to the enduring fundamental questions of biology.

Genomic imprinting refers to a recently discovered phenomenon in which the expression pattern of an allele depends on whether that allele was inherited from the mother or the father. This difference in expression strategy correlates with differences in the epigenetic state of the two alleles. These epigenetic differences include DNA methylation at CpG dinucleotides, as well as modifications on the histones associated with the locus. In the simplest possible cases, the promoter region of the imprinted gene is methylated during oogenesis, but not spermatogenesis (or vice versa). This methylation (and its accompanying histone modifications) results in inactivation of the modified allele. Of course, most imprinted genes do not fall into this simplest case. The goal of this book is neither to provide a basic introduction to imprinting, nor to provide a comprehensive survey of the current state of the field (which would necessarily span multiple books). Rather, the book covers on some of the more recent advances, with the goal of drawing attention to some of the emerging subtleties and complexities associated with imprinted genes.

This new edited volume in the Springer Subcellular Biochemistry Series presents a comprehensive, state-of-the-art overview of the proteomics of peroxisomes derived from mammalian, Drosophila, fungal, and plant origin, and contains contributions from leading experts in the field. The development of sensitive proteomics and mass spectrometry technologies, combined with bioinformatics approaches now allow the identification of low-abundance and transient peroxisomal proteins and permits to identify the complete proteome of peroxisomes, with the consequent increase of our knowledge of the metabolic and regulatory networks of these important cellular organelles. The book lines-up with these developments and is organized in four sections including: (i) mass spectrometry-based organelle proteomics; (ii) prediction of peroxisomal proteomes; (iii) analysis of peroxisome proteome interaction networks; and (iv) peroxisomes in relation to other subcellular compartments. The editor Luis A. del Rio is Professor ad honorem of the Spanish National Research Council (CSIC) in the Group of Antioxidants, Free Radicals and Nitric Oxide in Biotechnology, Food and Agriculture, Department of Biochemistry and Cell & Molecular Biology of Plants, at the Estacion Experimental del Zaidin, Granada, Spain. Del Rio's research group focuses on the metabolism of reactive oxygen species (ROS), reactive nitrogen species (RNS) and antioxidants in plant peroxisomes, and the ROS- and RNS-dependent role of peroxisomes in plant cell signalling. The editor Michael Schrader is Professor of Cell Biology & Cytopathology in the Department of Biosciences at the University of Exeter, UK. Using mammalian peroxisomes as model organelles, Prof. Schrader and his team aim to unravel the molecular machinery and signalling pathways that mediate and regulate the formation, dynamics and abundance of these medically relevant cellular compartments.

Precis This book is a treatise about the origin of cancers. I would like to convince readers that the basic tenets of the theory of a stem-cell origin of cancers also constitute a unified theory of cancer. Stem-cell origin of normal (and cancer) cells: Vitruvian version Every truth passes through three stages before it is recognized. In the first it is ridiculed, in the second, it is opposed, in the third, it is regarded as self-evident. - Arthur Schopenhauer v vi Preface Every person has a unique story to tell. My story is about cancer. Cancer touches the lives of countless people. Often enough, it leaves indelible tracks. Many lives have been lost; others are forever changed. For those who confront this deadly scourge, there is a sense of urgency, if not of desperation. For those who face im- nent death, life becomes even more precious and carries a special meaning. As an oncologist, I am touched daily by cancer. I feel its inception, evolution, and aft- math. It seems as though we are fighting an incessant war against cancer at the front line in the trenches. This is my story about cancer. Some people are terrific storytellers. Others have incredible tales to tell.

Laser microdissection techniques have revolutionized the ability of researchers in general, and pathologists in particular, to carry out molecular analysis on specific types of normal and diseased cells and to fully utilize the power of current molecular technologies including PCR, microarrays, and proteomics. In second edition of Laser Capture Microdissection: Methods and Protocols, experts in the field provide the reader with practical advice on how to carry out tissue-based laser microdissection successfully in their own laboratory using the different laser microdissection systems that are available and to apply a wide range of molecular technologies. The individual chapters encompass detailed descriptions of the individual laser based micro-dissection systems. The downstream applications of the laser microdissected tissue described in the book include PCR in its many different forms as well as gene expression analysis including application to microarrays and proteomics. 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 tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Laser Capture Microdissection: Methods and Protocols, Second Edition is an ideal resource for researchers striving to move forward our understanding of normal physiology and pathology.

The endothelins are a remarkable family of signaling peptides: molecular biology predicted the existence of their receptors and synthetic enzymes prior to both the identification of the encoded proteins and the synthesis of antagonists and inhibitors for use as pharmacological tools. Although considerable advances have been made, culminating in the design of endothelin antagonists with the- peutic potential in cardiovascular disease, much remains to be discovered. Tantalizingly, new research frontiers are emerging. To support further progress, Peptide Research Protocols: Endothelin encompasses experimental protocols that interrogate all facets of an endogenous mammalian peptide s- tem, from peptide and receptor expression through synthetic pathway to peptide function and potential role in human disease. Chapters describe the use of molecular techniques to quantify the expression of mRNA for both endothelin receptors and the endothelin-converting enzymes. Peptides, precursors, receptors, and synthetic enzymes may be localized and quantified in plasma, culture supernatants, tissue homogenates, and tissue s- tions using antibodies, while additional information on receptor characterization may be obtained using radioligand binding techniques. Several protocols cover in vitro assays that determine the function of the endothelin peptides in isolated preparations, that characterize new endothelin receptor ligands, or provide inf- mation on the tissue-specific processing of endothelin precursor peptides.

"Applied Computational Genomics" focuses on an in-depth review of statistical development and application in the area of human genomics including candidate gene mapping, linkage analysis, population-based, genome-wide association, exon sequencing and whole genome sequencing analysis. The authors are extremely experienced in the area of statistical genomics and will give a detailed introduction of the evolution in the field and critical evaluations of the advantages and disadvantages of the statistical models proposed. They will also share their views on a future shift toward translational biology. The book will be of value to human geneticists, medical doctors, health educators, policy makers, and graduate students majoring in biology, biostatistics, and bioinformatics. Dr. Yin Yao Shugart is investigator in the Intramural Research Program at the National Institute of Mental Health, Bethesda, Maryland USA. "

This volume contains 29 engrossing chapters contributed by worldwide, leading research groups in the field of chemical biology. Topics include pre-biology; the establishment of the genetic code; isomerization of RNA; damage of nucleobases in RNA; the dynamic structure of nucleic acids and their analogs in DNA replication, extra- and intra-cellular transport; molecular crowding by the use of ionic liquids; new technologies enabling the modification of gene expression via editing of therapeutic genes; the use of riboswitches; the modification of mRNA cap regions; new approaches to detect appropriately modified RNAs with EPR spectroscopy and the use of parallel and high-throughput techniques for the analysis of the structure and new functions of nucleic acids. This volume discusses how chemistry can add new frontiers to the field of nucleic acids in molecular medicine, biotechnology and nanotechnology and is not only an invaluable source of information to chemists, biochemists and life scientists but will also stimulate future research.

This volume presents a collection of computational and experimental protocols pertaining to the creation, characterization, and utilization of RNA nanostructures. The chapters in this book cover topics such as ion effects in RNA folding; design and crystallography of self-assembling RNA nanostructures; x-aptamer selection and validation; RNAi in HIV-infected cells; and preparation of a conditional RNA switch. 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, RNA Nanostructures: Methods and Protocols is a valuable resource for the design and production of RNA nanostructures. Researchers and scientists sharing these detailed protocols is important for sustained progress in the field.

Only in recent times has the possibility of growing and implanting replacement teeth, made from one s own cells, moved into the realm of realistic possibilities; however, the molecular and cellular mechanisms of tooth development must be studied in a range of vertebrates, from zebrafish to mice, so that evolutionarily conserved network kernels, which will define the cellular states of generic vertebrate tooth development, can be recognized. In "Odontogenesis: Methods and Protocols," experts in the field examine techniques to approach this burgeoning field. This detailed volume includes chapters on the detection of tooth development gene expression, both at the RNA and protein level, current approaches to the manipulation of gene expression levels and subsequent analysis of tooth phenotypes, as well as chapters concerning current efforts to get living tooth implants working without waiting for a full understanding of the developmental pathways at the molecular level. 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 for troubleshooting and avoiding known pitfalls.

Practical and easy to use, "Odontogenesis: Methods and Protocols" aims to help researchers move forward toward the ultimate goal of getting a bioengineered tooth into the patient s mouth.

During the past decade, geneticists have cloned scores of Mendelian disease genes and constructed a rough draft of the entire human genome. The unprecedented insights into human disease and evolution offered by mapping, cloning, and sequencing will transform medicine and agriculture. This revolution depends vitally on the contributions of applied mathematicians, statisticians, and computer scientists. Mathematical and Statistical Methods for Genetic Analysis is written to equip students in the mathematical sciences to understand and model the epidemiological and experimental data encountered in genetics research. Mathematical, statistical, and computational principles relevant to this task are developed hand in hand with applications to population genetics, gene mapping, risk prediction, testing of epidemiological hypotheses, molecular evolution, and DNA sequence analysis. Many specialized topics are covered that are currently accessible only in journal articles. This second edition expands the original edition by over 100 pages and includes new material on DNA sequence analysis, diffusion processes, binding domain identification, Bayesian estimation of haplotype frequencies, case-control association studies, the gamete competition model, QTL mapping and factor analysis, the Lander-Green-Kruglyak algorithm of pedigree analysis, and codon and rate variation models in molecular phylogeny. Sprinkled throughout the chapters are many new problems. Kenneth Lange is Professor of Biomathematics and Human Genetics at the UCLA School of Medicine. At various times during his career, he has held appointments at the University of New Hampshire, MIT, Harvard, and the University of Michigan. While at the University of Michigan, he was the Pharmacia & Upjohn Foundation Professor of Biostatistics. His research interests include human genetics, population modeling, biomedical imaging, computational statistics, and applied stochastic processes. Springer-Verlag published his book Numerical Analysis for Statisticians in 1999.

No one wants to be sued. A lawsuit is an assault on one 's self-image, reputation, and livelihood. It is physically, mentally, and financially draining. The purpose of this book is (1) to provide genetic counselors with varying levels of experience and expertise with heightened awareness of the sources and processes of the law as it can affect their practice; (2) to offer them strategies for minimizing the potential for their being named in a lawsuit; and (3) to provide guidance for the management of current and emerging situations. This is the first book specifically addressing genetic counseling, as opposed to general healthcare risk management.

Forensic DNA profiling procedures are mainly based on high resolution and high throughput capillary electrophoresis separation and detection systems of PCR amplicons obtained from DNA genomic markers with different inheritance patterns. In DNA Electrophoresis Protocols for Forensic Genetics, expert researchers in the field detail many of the protocols and methods which are now commonly used to perform forensic DNA profiling. It includes protocols for profiling of autosomal STRs, Y-STRs, X-STRs, autosomal SNPs, INDELS, Y-SNPs, mtDNA-SNPs, and mtDNA hypervariable regions HV1 and HV2 . Protocols for molecular identification of non-human species and mRNA profiling for body fluid identification are also included. 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.

The field of behavioral neurogenetics has developed significantly over the past two decades. This has been largely driven by technical advances in the field of molecular genetics both in model systems and in clinical analysis. Indeed, it is hoped that the elucidation and ongoing functionalisation of the human genome may provide new insights into the aetiology, course and, ultimately, treatment of psychiatric illnesses. This book covers a wide array of topics relevant to behavioral genetics from both a preclinical and clinical standpoint. Indeed in juxtaposing both areas of research the reader will appreciate the true translational nature of the field. Topics covered range from technical advances in genetic analysis in humans and animals to specific descriptions of advances in schizophrenia, attention disorders, depression and anxiety disorders, autism, aggression, neurodegeneration and neurodevelopmental disorders. The importance of gene-environment interactions is emphasised and the role of neuroimaging in unravelling the functional consequences of genetic variability described. This volume will be valued by both the basic scientist and clinician alike who may use it as a detailed reference book. It will also be of use to the novice to the field, to whom it will serve as an in-depth introduction to this exciting area of research.

The FactsBook Series has established itself as the best source of easily accessible and accurate facts about protein groups. They use an easy-to-follow format and are researched and compiled by experts in the field.
This Factsbook is devoted to nuclear receptors. The first section presents an introduction and describes the mode of action of the receptors in general. The second section of the book contains detailed entries covering each type of receptor.
Entries provide information on:
Nomenclature and structure
Isolation
DNA binding properties
Ligands
Expression
Target genes
Knockouts
Disease association
Gene structure, promoter and isoforms
Chromosomal location
Amino acid sequences
Key references

The rapid identification and characterization of genes of neurological relevance holds great potential for offering insight into the diagnosis, management, and und- standing of the pathophysiologic mechanisms of neurological diseases. This volume in the Methods in Molecular Biology (TM) series was conceived to highlight many of the contemporary methodological approaches utilized for the characterization of neu- logically relevant gene mutations and their protein products. Although an emphasis has been placed upon descriptions of methodologies with a defined clinical utility, it is hoped that Neurogenetics: Methods and Protocols will appeal not only to clinical laboratory diagnosticians, but also to clinicians, and to biomedical researchers with an interest in advances in disease diagnosis and the functional consequences of neu- logically relevant gene mutations. To meet this challenge, more than 60 authors graciously accepted my invitation to contribute to the 32 chapters of this book. Through their collective commitment and diligence, what has emerged is a comprehensive and timely treatise that covers many methodological aspects of mutation detection and screening, including disc- sions on quantitative PCR, trinucleotide repeat detection, sequence-based mutation detection, molecular detection of imprinted genes, fluorescence in situ hybridization (FISH), in vitro protein expression systems, and studies of protein expression and function. I would like to take this opportunity to formally thank my colleagues for their effort and dedication to this work.

This volume contains state-of-the-art methods tackling all aspects of small non-coding RNAs biology. Small Non-Coding RNAs: Methods and Protocols guides readers through customized dedicated protocols and technologies that will be of valuable help to all those willing to contribute deciphering the numerous functions of small non-coding RNAs. Written in the highly successful Methods of 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 troubles troubleshooting and avoiding known pitfalls. Instructive and practical, Small Non-Coding RNAs: Methods and Protocols reaches out to biochemists, cellular and molecular biologists already working in the field of RNA biology and to those just starting to study small non-coding RNAs.