Recent years have seen spectacular advances in the filed of epigenetics. These have attracted the interest of researchers in many fields and evidence connecting epigentic regulation to brain functions has been accumulationg. Neurons daily convert a variety of external stimuli into rapid or long-lasting changes in gene expression. A variety of studies have centered on the molcular mechanisms implicated in epigentic control and how these may operte in concert. It will be critical to unravel how specifity is achieved. The focus of this volume is on critical epigenetic regulation and chromatin remodeling events that occur in the nervous system and on the presumed mechanisms that operate within neurons to translate them into long-lasting neuronal responses.

Chemotherapy has made a dramatic difference to improved survival in patients with cancer. However, not all patients respond and some experience serious side effects. "Pharmacogenetics: Making cancer treatment safer and more effective" is an up to date summary of the exciting new field of how genetic testing can tailor more effective prescription in oncology. It is targeted at oncologists and professionals involved in the treatment of patients with cancer. It provides a core background in genetics and pharmacological principles before providing chapters from acknowledged experts in the field on genetic tests in specific cancer types, including breast, bowel and lung cancer. Clinical cases are used to illustrate the practical application of this knowledge. Chapters on ethics, health economics and the industry aspects of pharmacogenetics set out the challenges and opportunities afforded by this new science.

In 1925, J. B. Collip (1925) reported that extracts of parathyroid gland contained an activity that raised calcium levels in the blood of parathyroidectomized animals, and suggested that this was due to a hormone produced in the parathyroid gland. The story of parathyroid hormone discovery was indicative of ever-increasing sophistication in sample preparation and protein isolation techniques. This paper resolved earlier controversies over the function of the parathyroid glands and c- trol of blood calcium. The year 1961 was a banner year for parathyroid research, in which the peptides parathyroid hormone and calcitonin were purified, and in which it was suggested that calcitonin could lower blood calcium (Copp and Cameron 1961). In 1982 it was discovered that in neurons the primary RNA transcript for calcitonin could be alternatively-spliced to give calcitonin gene-reated peptide (CGRP), and shortly thereafter amylin (previously named islet amyloid polyp- tide, IAPP) was identified and shown to have homology to CGRP. Since then a and b CGRP have been delineated and adrenomedullin and intermedin discovered, and this family of homologous peptides has emerged. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition.

In this book internationally recognized investigators describe cutting-edge laboratory techniques for the study of Production and In Vivo Applications of Gene Transfer Vectors and Design and Characterization of Gene Transfer Vectors. Readers will find a comprehensive resource of current and emerging methods for the production of viral and non-viral gene transfer vectors, as well as detailed protocols for applications in stem cell biology, cancer research and infectious disease.

Paris is a cosmopolitan city where roaring life, wonderful museums and excellent science can be found. It was during the XI IUMS conference held in this city that the Pseudomonas book series was ?rst envisaged. On the ?rst row of the auditorium sat a group of outstanding scientists in the ?eld, who after devoting much of their valuable time, contributed in an exceptional manner to the ?rst three volumes of the series, which saw the light simultaneously. The volumes were grouped under the generic titles of "Vol. I. Pseudomonas: Genomics, Life Style and Molecular Architecture", Vol. II. Pseudomonas: Virulence and gene regulation; Vol. III. Pseudomonas: Biosynthesis of Macromolecules and Molecular Metabolism. Soon after the completion of the ?rst three volumes, a rapid search for ar- cles containing the word Pseudomonas in the title in the last 10 years produced over 6,000 articles! Consequently, not all possible topics relevant to this genus were covered in the three ?rst volumes. Since then two other volumes were p- lished: Pseudomonas volume IV edited by Roger Levesque and Juan L. Ramos that came to being with the intention of collecting some of the most relevant emerging new issues that had not been dealt with in the three previous volumes. This v- ume was arranged after the Pseudomonas meeting organized by Roger Levesque in Quebec (Canada). It dealt with various topics grouped under a common heading: "Pseudomonas: Molecular Biology of Emerging Issues".

In Gene Therapy Protocols, Volumes 1 and 2, internationally recognized investigators describe cutting-edge laboratory techniques for the study of Production and In Vivo Applications of Gene Transfer Vectors (Volume 1) and Design and Characterization of Gene Transfer Vectors (Volume 2). In this second volume, readers will find a comprehensive resource of current and emerging methods for the processing and characterization of viral and non-viral gene transfer vectors.

As our understanding of apoptotic pathway expands, we are coming to realize the great potential of utilizing this pathway to treat diseases such as cancer. The book attempts to review, summarize, and speculate on the apoptotic pathways, how are they regulated and how targeted therapies are being used to treat a wide variety of diseases. Special emphasis is placed on cancer since new treatments either being developed or currently in the clinical setting are showing great promise to increase survival rates for cancer patients. Chapters will address the biology behind regulating the apoptotic pathways and what goes wrong in disease states whereas other chapters will concentrate on new therapies targeting apoptotic pathways. The reader by the end of the book should have greater insight into the understanding and utilization of apoptotic pathways to fight diseases such as cancer.

This book offers comprehensive information on the polymorphisms of genes encoding pattern recognition receptors (PRRs). Following a short description of the general role of PRRs in the immune system, the structure and function of Toll-like and NOD-like receptors are examined in detail. The main focus is on the role of inherited variation in PRRs and their correlation to cancer and cardiovascular diseases. A review of all epidemiological investigations is included, and a concept of genomic risk markers for the prevention of various diseases is also discussed.

Next generation sequencing is revolutionizing molecular biology. Owing to this new technology it is now possible to carry out a panoply of experiments at an unprecedented low cost and high speed. These go from sequencing whole genomes, transcriptomes and small non-coding RNAs to description of methylated regions, identification protein - DNA interaction sites and detection of structural variation. The generation of gigabases of sequence information for each of this huge bandwidth of applications in just a few days makes the development of bioinformatics applications for next generation sequencing data analysis as urgent as challenging.

Cancer stem cells have originally been identified in leukemia and later in several solid tumor types. They have very different properties from the bulk of the tumor as they divide much more slowly and have very efficient drug resistance mechanisms. Current treatments might largely spare cancer stem cells. This book looks at recent developments in the field of cancer stem cells and the possible impact for the identification of novel treatment paradigms for cancer.

Hedgehog-GLI Signaling in Human Disease represents the first compilation of up-to-date reviews by top-level scientists in this important field of research. The chapters cover a wide spectrum of related interests, from the molecular bases of morphogen function, to human genetics to cancer research. The aim of the book is to disseminate information on this exciting field, to allow students, scientists and the public in general to gain access current information from research leaders and to provide a book that encompasses different aspects of research showing the fusion of basic research in model systems and medicine. This is a timely primer on how a system of cell communication, Hedgehog-GLI signaling, plays a critical role in human disease and thus provides the background for the development of novel and rational therapies.

As studies using microarray technology have evolved, so have the data analysis methods used to analyze these experiments. The CAMDA conference plays a role in this evolving field by providing a forum in which investors can analyze the same data sets using different methods. Methods of Microarray Data Analysis IV is the fourth book in this series, and focuses on the important issue of associating array data with a survival endpoint. Previous books in this series focused on classification (Volume I), pattern recognition (Volume II), and quality control issues (Volume III). In this volume, four lung cancer data sets are the focus of analysis. We highlight three tutorial papers, including one to assist with a basic understanding of lung cancer, a review of survival analysis in the gene expression literature, and a paper on replication. In addition, 14 papers presented at the conference are included. This book is an excellent reference for academic and industrial researchers who want to keep abreast of the state of the art of microarray data analysis. Jennifer Shoemaker is a faculty member in the Department of Biostatistics and Bioinformatics and the Director of the Bioinformatics Unit for the Cancer and Leukemia Group B Statistical Center, Duke University Medical Center. Simon Lin is a faculty member in the Department of Biostatistics and Bioinformatics and the Manager of the Duke Bioinformatics Shared Resource, Duke University Medical Center.

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.

Genetic Engineering: Principles and Methods presents state-of-the-art discussions in modern genetics and genetic engineering. Recent volumes have covered gene therapy research, genetic mapping, plant science and technology, transport protein biochemistry, and viral vectors in gene therapy, among many other topics. Key features of Volume 27 include: - Identification and Analysis of Micrornas - Dormancy and the Cell Cycle - Long distance peptide and metal transport in plants - Signaling in plant response to temperature and water stresses - Nutrient transport and metabolism in plants - Salt Stress Signaling and Mechanisms of Plant Salt Tolerance - Gene cloning and expression - Assisted folding and assembly of proteins

"Your genome is an email attachment" What a difference a few years can make? In 2001, to a global fanfare, the completion of the frst draft sequence of the human genome was announced. This had been a Herculean effort, involving thousands of researchers and millions of dollars. Today, a project to re-sequence 1,000 genomes is well underway, and within a year or two, your own "personal genome" is likely to be available for a few thousand pounds, a price that will undoubtedly decrease further. We are fast approaching the day when your genome will be available as an email attachment (about 4 Mb). The key to this feat is the fact that any two human genomes are more than 99% identical, so rather than representing every base, there is really only a requirement to store the 1% of variable sequence judged against a common reference genome. This brings us directly to the focus of this edition of Methods in Molecular Biology, Genetic Variation. The human genome was once the focus of biology, but now individual genome var- tion is taking the center stage. This new focus on individual variation ultimately democ- tizes biology, offering individuals insight into their own phenotype. But these advances also raise huge concerns of data misuse, misinterpretation, and misunderstanding. The immediacy of individual genomes also serves to highlight our relative ignorance of human genetic variation, underlining the need for more studies of the nature and impact of genetic variation on human phenotypes.

This handbook offers guidance on selections of appropriate computational methods and software packages for specific genetic problems. Coverage strikes a balance between methodological expositions and practical guidelines for software selections. Wherever possible, comparisons among competing methods and software are made to highlight the relative advantages and disadvantage of the approaches.

Gabriel Waksman Institute of Structural Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, United Kingdom Address for correspondence: Professor Gabriel Waksman Institute of Structural Molecular Biology Birkbeck and University College London Malet Street London WC1E 7H United Kingdom Email: g. waksman@bbk. ac. uk and g. waksman@ucl. ac. uk Phone: (+44) (0) 207 631 6833 Fax: (+44) (0) 207 631 6833 URL: http://people. cryst. bbk. ac. uk/?ubcg54a Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of Structural Molecular Biology at UCL/Birkbeck, of which he is also the director. Before joining the faculty of UCL and Birkbeck, he was the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine in St Louis (USA). The rapidly evolving ?eld of protein science has now come to realize the ubiquity and importance of protein-protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of hi- throughput proteomics to monitor protein-protein interactions at an organism level, we can now safely state that protein-protein interactions are the norm and not the exception.

Different genetic diagnostic and treatment options are used worldwide to improve routine IVF procedures for the benefit of patients. This handbook updates the new genetic diagnostic technologies that have been translated to the clinic, aiming to improve outcomes in the clinic and result in a healthy baby in the home. Chapters cover the use of genetic technologies in a personalized manner to unravel the possible genetic risks for the couple wishing to conceive, in terms of sperm, the embryo, the endometrium, miscarriage, and finally the fetus. This expanded new edition covers the range of the latest genetic diagnostic technologies being translated into practice internationally to improve routine IVF procedures for the benefit of patients. Bringing together international experts to discuss their work, this text gives a context for the developments in this very fast-moving area of research and offers a comprehensive and rounded appraisal of hot topics.

DNA and RNA fractions have been isolated from the whole blood, serum, plasma, the surface of blood cells, urine, saliva and spinal fluid from both healthy individuals and clinical patients. Recent developments are presented concerning the isolation, quantification and analysis of these molecules and their use in the identification of specific nucleic acid fragments related to a variety of clinical disorders thereby permitting their early diagnosis and prognosis.

MicroRNA (miRNA) is a cutting-edge topic in the scientific and medical fields. This is a timely and specialized book focusing on the current understanding of miRNAs and the potential for their application in cancer diagnosis, prognosis, and therapeutic targets. It also provides discussion of the lessons learned from translational miRNA studies and exploration of the next steps required to advance this field. The unique book comprises 22 in-depth chapters by gathering unparalleled topics of interest in miRNAs by international team of world-renowned experts in the field. The first fifteen chapters provide comprehensive and expert perspectives on the most common cancers from bench to bedside applications, there is no current book structured in this cancer-oriented way. The next seven chapters providing thorough overviews of miRNAs and cancer stem cells; miRNAs in cancer invasion and metastasis; miRNAs in predicting radiotherapy and chemotherapy response; as well as expounding the role of miRNA in anti-cancer drug resistance and as blood-based cancer biomarkers. Furthermore, this book explicates the interplay of miRNAs in cancer metabolism and an update on the pioneering RNAi-based treatment approaches is also presented. This specialized book will contribute great to the scientific and medical community by providing the up-to-date discoveries of miRNAs and their important roles in cancer translational research.

The purpose of this book is to provide an up to date review of the nature and consequences of epigenetic changes in cancer. Epigenetics literally means "above" genetics, and consists of heritable gene expression or other phenotypic states not accounted for by DNA base sequence. Epigenetic changes are now known to make a large contribution to various aspects of tumorigenesis. These changes include alterations in global and promoter specific DNA methylation, activating and repressive histone modifications, and changes in higher order chromatin structures. Each of these topics will be covered in this book.

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

Known for flexibility and robustness, PCR techniques continue to improve through numerous developments, including the identification of thermostable DNA polymerases which exhibit a range of properties to suit given applications. PCR Protocols, Third Edition selects recently developed tools and tricks, contributed by field-leading authors, for the significant value that they add to more generally established methods. Along with the cutting-edge methodologies, this volume describes many core applications, such as PCR cloning and sequencing, expression, copy number or methylation profile analysis, 'DNA fingerprinting', diagnostics, protein engineering, interaction screening as well as a chapter highlighting workflow considerations and contamination control, crucial for all PCR methods. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary reagents and materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, PCR Protocols, Third Edition seeks to further elucidate this essential technique while also providing core principles with broad applications for scientists of all backgrounds.

The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the "DNA damage response". This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

Genomics in Endocrinology focuses on exciting new advances in endocrinology resulting from DNA microarray studies and includes a comprehensive introduction to the use of DNA microarrays in endocrinology. The text provides the basis for further understanding of the usefulness of microarray analyses in endocrinology research. Topics discussed include the methodology of DNA microarrays and general methods for the analysis of microarray data.