In the past two decades we have seen a surge forward in understanding the genetics and biochemistry underlying many pediatric orthopaedic disorders. A few projects have even progressed into the realm of clinical trials that are primarily aimed at controlling progressive disease. Meanwhile, genomic technology development has outpaced expectations and is enabling gene discovery for disorders that were previously intractable with traditional genetic methods. Included in this latter category are common disorders that display multigenic inheritance, sporadic disorders, and very rare conditions that are difficult to ascertain. Simultaneously, the study of pediatric orthopaedic disorders has been continuously refined and updated, highlighting a number of likely genetic conditions that are as yet unsolved. Molecular Genetics of Pediatric Orthopaedic Disorders updates researchers and clinicians of new developments of pediatric orthopaedic genetics. The chapters inform the audience on the revolution in new genomic methods and the impact this is having on potential study designs and the potential to discover genetic causes of many unsolved orthopaedic conditions. Recent examples have been included of pediatric orthopaedic conditions, both rare and common, that are being solved with these new methods. The book also educates pediatric orthopedic clinicians and geneticists on our understanding of the biology of "classic" genetic diseases that were derived from prior genetic studies. Chapters include biobanks and strategies for studying very rare disorders, genes and pathways causing primordial dwarfism, and notch signaling in congenital scoliosis, and more.

In Gene Regulatory Sequences and Human Disease, the Editor will introduce the different technological advances that led to this breakthrough. In addition, several examples will be provided of nucleotide variants in noncoding sequences that have been shown to be associated with various human diseases.

Fluorescence in situ Hybridization (FISH) belongs to that special category of well-established molecular biology techniques that, since their inception a few decades ago, have succeeded in keeping a prominent position within the constantly expanding list of laboratory pro- dures for biomedical research and clinical diagnostics. The design simplicity and cost-effectiveness of the early FISH protocols, combined with the signifcant acceleration of discoveries in related technical areas such as fuor- cence microscopy, digital imaging, and nucleic acid technology have prompted the div- sifcation of the original technique into an outstanding number of imaginative and useful applications, and thus have not only held back its outmoding but have also promoted its expansion into different areas of basic and applied research in the post-genomic era. The 34 chapters included in this book aim at portraying the vibrant complexity and diversity of the current FISH protocol landscape, providing cutting-edge examples of va- ous applications for genetic and developmental research, cancer research, reproductive medicine, diagnostic and prognostic purposes, microbial ecology, and evolutionary st- ies. The book is divided in four parts: (I) Core Techniques, (II) Technical Advancements and Novel Adaptations, (III) Translational FISH: Applications for Human Genetics and Medicine, and (IV) Protocols for Model Organisms.

The field of genetics is rapidly evolving, and new medical breakthroughs are occurring as a result of advances in our knowledge of genetics. This series continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. This thematicvolume reviews the latest research findings in the area of vascular proteomics related to the receptors of the vascular endothelium, and expands insights into diseases that exhibit distinct vascular characteristics, including cancer, obesity, andinflammation.

* Provides contrasting roles of VEGF, givingresearchers a better understanding of the underlying mechanisms of VEGF *Includeschapters that review research employing a variety of organisms, allowing researchers to compare and contrast *Focuses onmaterial that translates basic research to real-life treatment applications, showing primary researchers how the basic science is being used in the clinical setting"

In Polyadenylation: Methods and Protocols, expert researchers in the field detail many of the protocols which are now commonly used to study polyadenylation. Focusing on recent advances in the fast-moving polyadenylation filed, that has recently been recognized as a key contributor to the complexity of mammalian gene expression. 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.

This issue on psychiatric genetics gives a clinically-minded approach to the newest thinking in genetics and pharmacogenomics, including articles on genetic epidemiology; molecular approaches; epigenetics; and genetic considerations in schizophrenia, bipolar disorder, major depression, obsessive-compulsive disorder, alzheimer's disease, autism, ADHD, and addictions. The issue concludes with articles on diagnostic testing, and pharmacogenomics.

This book combines the most recent knowledge on the maternal, i.e. oocyte/egg-specific, molecules and processes. The volume covers the most recent advances in a plethora of subjects such as: maternal transfer of immunity, localized RNAs functions and mechanisms of RNA localization, transcriptional repression of maternal messages, maternal inheritance and maternal role of CRISPR/Cas9-based genome editing, chromatin remodeling and epigenetic modifications, maternal function of nucleosomes, maternal mitochondria and energy supply, role of bacterial symbionts and their maternal transmission, acquisition of oocyte polarity and evolution of maternal effect genes, germ plasm and oosome origin and functions, mechanisms of oocyte activation and soma germ cells communication. Currently, no other book on the market combines such a comprehensive list of subjects in one volume. Moreover, the information provided is a cross-section through oocytes from various invertebrate and vertebrate species, which is another unique feature of this book. The readers, therefore, get a completely new and invaluable perspective on all covered subjects.

This book evolved from the editors strong belief that the information and new developments that were evolving from the rapidly growing field of genomics and that are happening primarily in the developed world have not happened at a parallel rate in the developing world. One would have hoped that by now the technologies and approaches would have been adapted on a far greater scale. In addition to this, the associated information is not always easily accessible, and is not disseminated in a format that can become a useful reference for scientists, students and others who reside in developing countries.

Epigenetics has emerged recently as an important area of molecular biological studies. Epigenetic modifications lead to potentially heritable but reversible alterations in the expression of genes that determine cell fate. Epigenetic misregulation is thus often linked to degenerative diseases, cancer and neuronal disorders. Recent biomedical interest in this regulatory system stems from the fact that epigenetic, in contrast to genetic, alterations are in principle amenable to pharmacological intervention. A few epigenetically active drugs, for example histone deacetylase inhibitors (HDACi) and DNA methyltransferase (DNMT) inhibitors, have been approved by FDA for treatment of cancers such as CTCL, MDS, and AML. This volume explores the scientific background for clinical applications of epigenetically active drugs. Included are descriptions of epigenetic controls over gene expression, the post-transcriptional silencing of genes by RNA interference (RNAi) and microRNAs, as well as new findings from stem cell research which are relevant to pharmacological applications. Content Level Research

Together with early theoretical work in population genetics, the debate on sources of genetic makeup initiated by proponents of the neutral theory made a solid contribution to the spectacular growth in statistical methodologies for molecular evolution. Evolutionary Genomics: Statistical and Computational Methods is intended to bring together the more recent developments in the statistical methodology and the challenges that followed as a result of rapidly improving sequencing technologies. Presented by top scientists from a variety of disciplines, the collection includes a wide spectrum of articles encompassing theoretical works and hands-on tutorials, as well as many reviews with key biological insight. Volume 1 includes a helpful introductory section of bioinformatician primers followed by detailed chapters detailing genomic data assembly, alignment, and homology inference as well as insights into genome evolution from statistical analyses. Written in the highly successful Methods in Molecular Biology (TM) series format, this work provides the kind of advice on methodology and implementation that is crucial for getting ahead in genomic data analyses. Comprehensive and cutting-edge, Evolutionary Genomics: Statistical and Computational Methods is a treasure chest of state-of the-art methods to study genomic and omics data, certain to inspire both young and experienced readers to join the interdisciplinary field of evolutionary genomics.

Ataxia-telangiectasia (A-T) is a rare and severe genetic disorder affecting children. A-T is a multisystem disease characterized by progressive neurodegeneration, immunodeficiency and cancer predisposition. This detailed volume explores the ever expanding field of research into the ATM (ataxia-telangiectasia, mutated) gene and the role played by ATM kinase in DNA damage signaling and diverse cellular processes. What follows is a handy desktop reference for both seasoned A-T researchers and postgraduate students, as it demonstrates the breadth of recent developments in A-T studies. Written for the highly successful Methods in Molecular Biology series, 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. Both classic and cutting-edge techniques are described, including ATM gene mutation detection, assays for radiosensitivity and radioresistant DNA synthesis, new methods to measure ATM kinase activity by imaging microscopy and high content screening as well as proteomics, phosphoproteomics and bioinformatics approaches to decipher ATM-dependent signalling pathways. Additional methods include generation of patient-specific stem cells and approaches to study ATM functions in the nervous system. Comprehensive and practical, ATM Kinase: Methods and Protocols aims to ignite and attract the interest of colleagues from diverse fields to A-T research in an effort to bring their expertise and fresh ideas to resolve many A-T puzzles still waiting to be pieced together and to alleviate the suffering of A-T children and their families.

This volume provides the reader with a pathophysiological perspective on the role of CNS in puberty and adolescence, starting from genetic/molecular aspects, going through structural/imaging changes and leading to physical/behavioral characteristics. Therefore, renowned investigators involved in both animal and human research shared recent data as well as overall appraisal of relevant questions around CNS control of puberty and adolescence. No doubt that this volume will inspire those involved in either scientific research or clinical practice or both in the fascinating field of puberty and adolescence.

Since the discovery of microRNAs, developmental biologists have striven to understand the role of miRNAs in development and disease. MicroRNAs in Development: Methods and Protocols collects contributions from expert researchers in order to provide practical guidelines to this complex study. Divided into three convenient sections, this detailed volume covers various techniques to detect and profile miRNA expression, followed by protocols to manipulate the activity of miRNAs in various organisms, and it concludes with a section that outlines different methods to identify and validate miRNA targets in animals and plants. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, MicroRNAs in Development: Methods and Protocols serves as a practical guide for scientists of all backgrounds and conveys the appropriate sense of fascination associated with this vital field of research.

Two sigma receptor subtypes have been proposed, sigma1 and 2. Much of our understanding of this system is based on biochemical and pharmacological characterization of the cloned sigma1 receptor subtype (Sigma1). It has become clear that sigma receptors are not canonical receptors. Sigma1 is highly conserved among mammalian species, however, it does not share significant homology with any other mammalian protein. Although a range of structurally diverse small molecules bind Sigma1 with high affinity, and it has been associated with a broad range of signaling systems, Sigma1 itself has no known signaling or enzymatic activity. The evolution of this field over nearly four decades has more recently led to a fundamental shift in the concept of "sigma receptors" to what may more accurately and generally be called sigma proteins. Largely based on traditional pharmacologic approaches, the Sigma1 protein has been associated with a broad range of signaling systems, including G-protein coupled receptors, NMDA receptors, and ion channels. Sigma proteins have been linked to a range of physiological processes, including intracellular calcium signaling, neuroprotection, learning, memory, and cognition. Emerging genetic, clinical, and mechanism focused molecular pharmacology data demonstrate the involvement of proteins in a range of pathophysiologies and disorders including neurodegenerative disease, pain, addiction, psychomotor stimulant abuse, and cancer. However, an understanding of the physiological role of sigma proteins has remained elusive. Emerging data associate Sigma1 with chaperone-like activities or molecular scaffold functions. This book aims to provide an updated perspective on this rapidly evolving field undergoing changes in fundamental concepts of key importance to the discipline of pharmacology. It focusses on the reported roles of sigma proteins in pathophysiology and on emergent therapeutic initiatives.

DNA Tumor Viruses will focus on the DNA viruses in the human population that are associated with cancers. It will cover most of the viruses that are thought to contribute to human malignancy.

This book will represent a comprehensive review of the field of DNA tumor virology. Right now, while there are books out there that cover individual viruses that will be also covered in this book, there is no single book that covers this topic comprehensively.

The main textbook in this market, Fields, which is referred to by both reviewers, covers some of these topics but on a lower level. The only two books that are nearly as comprehensive as this one are Human Tumor Viruses, which was published by the American Society for Microbiology in 1998 and is quite outdated, and Viruses, Cell Transformation, and Cancer, which was published by Elsevier in 2001. Our book will be the only current, comprehensive review of its kind in the market.

This detailed volume presents a comprehensive technical overview of DNA nanotechnology with an emphasis on 3D DNA nanostructure design and applications. Coverage spans from basic design principles for DNA and RNA nanostructures to their cutting-edge applications in a variety of fields, with the book divided into basic DNA and RNA nanostructure design strategies as well as applications utilizing DNA nanostructures, including but not limited to nanomedicine, bioimaging, biosensing, nanoplasmonics, nanoelectronics, nanofabrication, crystallography, biophysics, and analytical chemistry. Written for the highly successful Methods in Molecular Biology series, 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 authoritative, 3D DNA Nanostructure: Methods and Protocols provides the most up-to-date tutorial style overviews and technical style protocols to benefit researchers in a wide variety of areas.

This book presents a collection of articles on various aspects of current research on aging. These include model systems, cellular, biochemical and molecular aspects of experimental aging research, as well as selected intervention studies on age-related diseases. Aging is a global challenge to human society. Children are always in a hurry to become adults, while adults produce offspring and add to the gene pool. However, after adulthood or the attainment of reproductive maturity, all physiological parameters of the living organism start to undergo the aging process. Old age sets in slowly but surely, and usually continues for a prolonged period. If vigor and vitality are the main advantages of adulthood, old age offers the rewards of experience and maturity. Biologists ask questions such as: Why do we age? How do we become old? Is it possible to slow down, postpone or even prevent aging? In turn, medical experts ask: What are the diseases associated with old age? Are there medicines that can help affected elderly patients? In fact both groups are asking themselves how can we add more health to old age. Healthy aging is the dream of every individual. But to achieve this, it is fundamental that we first understand the cellular, biochemical and molecular basis of the aging process in mammalian cells, tissues and intact living organisms, which can serve as experimental model systems in Biomedical Gerontology. Once the biology of aging is understood at the genetic and molecular levels, interventional approaches to aging and its associated diseases may be easier to plan and implement at the preclinical level.

Gene therapy offers many conceptual advantages to treat muscle diseases, especially various forms of muscular dystrophies; however, it faces a number of unique challenges, including the need to deliver a therapeutic vector to all muscles throughout the body. In Muscle Gene Therapy: Methods and Protocols, expert researchers in the field present a collection of techniques aimed at bridging the translational gap in muscle gene therapy between the prevalent rodent models and vitally important larger animal models. Divided into three sections, this volume examines basic protocols for optimizing the muscle gene expression cassette and for evaluating the therapeutic outcomes, new developments in muscle gene therapy technology such as adeno-associated viral vector (AAV), oligonucleotide-mediated exon-skipping, and novel RNA-based strategies, and step-by-step guidance on muscle gene delivery in swine, ovine, canine, and non-human primates. 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, detailed, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Muscle Gene Therapy: Methods and Protocols serves as an invaluable resource for graduate students, post-doctoral fellows, and principle investigators pursuing the crucial advancement of muscle disease gene therapy in the hope of someday curing these debilitating disorders.

This project follows on the success of the book "25 years of p53", published by Springer in 2006. Since this publication, there have been considerable advances on the potential application of p53 into the clinics. The goal of this book is to capture these developments and to appeal to a clinical and medical audience beyond the one which was the primary target of "25 years of p53".

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.

Interest in the therapeutic value of embryonic, fetal and adult stem cell types is rapidly expanding throughout the scientific community. The first half of this century should see an explosion of therapeutic applications of stem cells which will grow from the cells and techniques described in this book. Stem Cell Culture provides a comprehensive resource for researchers in the fields of embryonic, fetal and adult stem cell biology to find methods for the purification, culture, and differentiation of these cell types, with the main emphasis on the maintenance of the stem cell phenotype in vitro. This volume will be the first to broadly cover multiple types of stem cell culture from different ages, organs and species. Chapters focus on the practical do's and don'ts of isolating and culturing these cell types, and use illustrative data or diagrams that allow the reader to confidently apply techniques and make this a standard reference.
*Compares and contrasts a broad range of species and stem cell types.
*Describes techniques in stem cell research, and goes beyond just protocols by presenting methods within perspective of recent literature reviews.
*Delineates critical steps and potential pitfalls for each method, provided by at-the-bench authors for expert information.
*Covers specific procedures in dealing with Human Embryonic Stem Cells, but also emphasizes other sources of potentially therapeutic stem cells such as amniotic fluid, adult muscle and adipose tissue, and umbilical cord.

This detailed volume provides a collection of protocols for the study of miRNA functions in plants. Beginning with coverage of miRNA function, biogenesis, activity, and evolution in plants, the book continues by guiding readers through methods on the identification and detection of plant miRNAs, bioinformatic analyses, and strategies for functional analyses of miRNAs. 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. Authoritative and cutting-edge, Plant MicroRNAs: Method and Protocols aims to ensure successful results in the further study of this vital area of plant science.

This book provides readers an extensive overview of recent progress in basic and clinical research on cancer immunotherapy. Thanks to rapid advances in molecular biology and immunology, it has become increasingly evident that cancer growth is influenced by host immune responses. With the success of a number of clinical trials, immunotherapy has become a promising treatment modality of cancer. This book covers five major topics, including monoclonal antibodies, biological response modifiers, cancer vaccines, adoptive cellular therapy and oncolytic viruses. It also examines the combination of different immune strategies as well as the combination of immunotherapy with other treatments to increase anti-tumor effects. Through the comprehensive discussion of the topic, the book sheds valuable new light on the treatment of tumors.

This text explores the most recent advances in NGS instrumentation and data anlysis. It begins with a comprehensive description of current NSG platforms, their sequencing chemistries, instrument specifications, and general workflows and procedures. A separate chapter is dedicated to low-quanitity, single molecule sequencing technology. Further chapters explore the application of NSG technologies in various fields.

Obesity is currently regarded as one of the major health challenges of the developed world. Excess body weight is an important risk factor for morbidity and mortality from cardiovascular diseases, diabetes, cancer, musculoskeletal disorders and even psychiatric problems and is estimated to cause nearly 3 million deaths per year worldwide. Obesity is not necessarily associated with comorbidities: there are indeed metabolically healthy obese individuals. Thus, we need to consider individuals presenting simple with obesity separately from those at risk of developing or who have already developed complex clinical states potentially leading to disability. Comorbidities can tip the balance of independence in patients who already have functional limitations mainly due to the excess of mass itself or who develop conditions such as diabetes, cardiovascular conditions, non-alcoholic fatty liver disease, where an abnormal metabolism of adipose tissue prevails. Morbid obesity with comorbidities leading to disability represents a real social and economic burden for National Health Systems worldwide. The presence of multiple and associated comorbidities often represents an obstacle to being admitted to hospitals for the treatment of metabolic diseases. On the other hand, clinical units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aim of this book is to focus on the pathophysiological and rehabilitative aspects of disabling obesity, highlighting multidisciplinary rehabilitation interventions as key to counteracting the disabling aspects of complicated obesity.