New genes and diversity leading to adaptation and evolution are generated in special areas of genomes. One such area in all eukaryotic genomes and in those prokaryotes with linear chromosomes is the region near the ends of the chromosomes. These telomere-associated sequences or subtelomeres, have different properties than the rest of the genome and are one of the most exciting frontiers left in genomics.

This book provides a broad introduction to the field of subtelomeres with detailed information from various fields and systems, covering yeasts and fungi, pathogens and parasites, plants, insects, humans and primates and bacteria with linear chromosomes. Advances in the field as well as continuing challenges are discussed throughout. The mosaic nature of this collection and the everchanging perspectives reflect the nature of subtelomeres themselves.

Unlike the core of most genomes, which are conserved and stable over time, subtelomeres are dynamic and polymorphic, so much so that generally no two individuals look alike in these regions. The dynamic nature of the region and the ability to change the copy number, generate diversity and try novel combinations make it the evolutionary tinker s toolbox. In many organisms the genes found in the region are involved in dealing with the environment. In yeasts, different gene families involved in sugar metabolism as well as clumping together are found in subtelomeres and differences in the region may be the reason why some strains are good for baking, others for brewing and why some are pathogenic. In fungal plant and animal pathogens, many of the genes involved in virulence are found here. In humans and primates there are a number of gene families that vary between ends, for example the diverse olfactory receptor genes. Even in bacterial linear chromosomes the region contains genes involved in adapting to their environments. Perhaps the ultimate use of these regions is in parasites where they rapidly adapt and escape from host immune systems through dynamic changes to the proteins exposed to the host s defenses. Such dynamic, polymorphic structures are also found in plants and insects though it is not always clear what the function might be; in some cases they take on the role of end maintenance. The dynamic, polymorphic nature of subtelomeres, where many ends share segmental duplications, is an exciting area for study but also presents a difficult challenge from the technical perspective."

This book will describe the nuclear encoded genes and their expressed proteins of mitochondrial oxidative phosphorylation. Most of these genes occur in eukaryotic cells, but not in bacteria or archaea. The main function of mitochondria, the synthesis of ATP, is performed at subunits of proton pumps (complexes I, III, IV and V), which are encoded on mitochondrial DNA. The nuclear encoded subunits have mostly a regulatory function. However, the specific physiological functions of the nuclear encoded subunits of complexes I, III, IV, and V are mostly unknown. New data indicates that they are essential for life of higher organisms, which is characterized by an adult life without cell division (postmeiotic stage) in most tissues, after the juvenile growth. For complex IV (cytochrome c oxidase) some of these subunits occur in tissue-specific (subunits IV, VIa, VIb, VIIa, VIII), developmental-specific (subunits IV, VIa, and VIIa) as well as species-specific isoforms. Defective genes of some subunits were shown to induce mitochondrial diseases. Mitochondrial genes and human diseases will also be covered.

The 3rd World Congress on Genetics, Geriatrics, and Neurodegenerative Disease Research (GeNeDis 2018), focuses on recent advances in genetics, geriatrics, and neurodegeneration, ranging from basic science to clinical and pharmaceutical developments. It also provides an international forum for the latest scientific discoveries, medical practices, and care initiatives. Advanced information technologies are discussed, including the basic research, implementation of medico-social policies, and the European and global issues in the funding of long-term care for elderly people.

Long non-coding RNAs (lncRNAs), tentatively defined as ncRNAs of more than two hundred nucleotides in length, are characterized by the complexity and diversity of their sequences and mechanisms of action. Based on genome-wide studies, more than 3,300 of them exist, but to date only the limited number of functional lncRNAs have been identified and characterized. Nonetheless, lncRNAs have emerged as key molecules involved in the control of transcriptional and posttranscriptional gene regulatory pathways. They take part in the recruitment of chromatin modifying complexes and regulate splicing, localization, stability and translation of the target mRNAs. This book provides an overview of the rapidly advancing field of long ncRNAs, describing the epigenetic and non-epigenetic mechanisms by which they regulate various biological functions in model systems, from yeast to mammals. The role of ncRNAs in sex chromosome dosage compensation in flies and mammals is described, as well as their role in centromere and telomere biology. Long non-coding RNAs involved in environmental stress response and development are presented and their mechanisms of action discussed.

Cell Therapy: cGMP Facilities and Manufacturing is the source for a complete discussion of facility design and operation with practical approaches to a variety of day-to-day activities, such as staff training and competency, cleaning procedures, and environmental monitoring. This in-depth book also includes detailed reviews of quality, the framework of regulations, and professional standards. It meets a previously unmet need for a thorough facility-focused resource, Cell Therapy: cGMP Facilities and Manufacturing will be an important addition to the cell therapy professionala (TM)s library.

Additional topics in Cell Therapy: cGMP Facilities and Manufacturinga ]

• Standard operating procedures
• Supply management
• Facility equipment
• Product manufacturing, review, release and administration
• Facility master file

Now in its third edition and supplemented with more online material, this book aims to make the "new" information-based (rather than gene-based) bioinformatics intelligible both to the "bio" people and the "info" people. Books on bioinformatics have traditionally served gene-hunters, and biologists who wish to construct family trees showing tidy lines of descent. While dealing extensively with the exciting topics of gene discovery and database-searching, such books have hardly considered genomes as information channels through which multiple forms and levels of information have passed through the generations. This "new bioinformatics" contrasts with the "old" gene-based bioinformatics that so preoccupies previous texts. Forms of information that we are familiar with (mental, textual) are related to forms with which we are less familiar (hereditary). The book extends a line of evolutionary thought that leads from the nineteenth century (Darwin, Butler, Romanes, Bateson), through the twentieth (Goldschmidt, White), and into the twenty first (the final works of the late Stephen Jay Gould). Long an area of controversy, diverging views may now be reconciled.

The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10-13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

This book deals with the paradoxical role of autophagy in tumor suppression and tumor promotion in cancer cells. Autophagy plays opposing, context-dependent roles in tumors; accordingly, strategies based on inhibiting or stimulating autophagy could offer as potential cancer therapies. The book elucidates the physiological role of autophagy in modulating cancer metastasis, which is the primary cause of cancer-associated mortality. Further, it reviews its role in the differentiation, development, and activation of multiple immune cells, and its potential applications in tumor immunotherapy. In addition, it examines the effect of epigenetic modifications of autophagy-associated genes in regulating tumor growth and therapeutic response and summarizes autophagy's role in the development of resistance to a variety of anti-cancer drugs in cancer cells. In closing, it assesses autophagy as a potential therapeutic target for cancer treatment. Given its scope, the book offers a valuable asset for all oncologists and researchers who wish to understand the potential role of autophagy in tumor biology.

Insulin-like growth factors (IGFs), their binding proteins and their receptors play important roles in regulating growth, metabolism, proliferation and survival for many cells and tissues throughout lifespan in humans and other species. Circulating IGF1 is known to be an endocrine regulator, with metabolic effects related to, and partly convergent with, insulin signalling. IGF1 also mediates many of the growth promoting effects of GH, and there is an ongoing debate as to the relative contributions of endocrine-, vs locally-derived IGF1 for systemic growth. More recently however, it has become clear that IGFs may be key local growth and cellular survival factors for many different tissues, active from early in embryonic development, essential for normal maturation and growth during foetal life. IGFs continue to play important roles throughout adult life in many diverse processes such as tissue repair, cellular proliferation, tissue remodelling and metabolic regulation. IGF systems are tightly regulated; orderly control of cellular repair and metabolism is central to healthy ageing, whilst uncontrolled proliferation can lead to cancer.

This cutting-edge book brings advances in genetics, neurobiology, and psychopharmacology to the clinic to enhance treatment for neurodevelopmental disorders. Significant progress has been made in identifying the neurobiological mechanisms of several disorders and targeted treatments are modifying the outcome of these disorders. However, the ability to utilize this knowledge has not been summarized in one place for the practicing clinician. This book will fill that gap by providing the theoretical underpinnings and the latest advances in targeted treatments. Several neurodevelopmental disorders are reviewed in detail including clinical features and behavioral phenotypes, standard treatments and new targeted treatments based on the latest advances in neurobiology and the animal model studies that have lead to new treatments. The disorders covered include psychiatric disorders: schizophrenia, depression, autism and ADHD; single gene disorders including Tuberous Sclerosis, Fragile X Syndrome and fragile X- associated disorders, Angelman Syndrome, PKU, and Muscular Dystrophies; and complex genetic disorders such as Down syndrome. This book also highlights the commonalities across disorders and new genetic and molecular concepts in an easy to read format. This is a very exciting time for new targeted treatments and this volume is a landmark treatise on this new age of treatment.

This edited reflects the current state of knowledge about the role of microRNAs in the formation and progression of solid tumours. The main focus lies on computational methods and applications, together with cutting edge experimental techniques that are used to approach all aspects of microRNA regulation in cancer. We are sure that the emergence of high-throughput quantitative techniques will make this integrative approach absolutely necessary in the near future. This book will be a resource for researchers starting out with cancer microRNA research, but is also intended for the experienced researcher who wants to incorporate concepts and tools from systems biology and bioinformatics into his work. Bioinformaticians and modellers are provided with a general perspective on microRNA biology in cancer, and the state-of-the-art in computational microRNA biology.

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 generation of genetically modified mice is absolutely crucial to gene function studies today, primarily because mice are genetically similar to man and because gene function studies in mice are in the context of a whole organism, making them particularly useful. In Transgenic Mouse Methods and Protocols, Second Edition, expert research explore current advances in the field through detailed laboratory protocols. Chapters provide a general introduction outlining how to deal with mice and how to generate transgenic mouse models, explore the generation of conditional and induced knockout and transgenic mice, and offer alternative routes to studying gene function in mice. Composed in the highly successful Methods in Molecular Biology (TM) series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Comprehensive and state of the art, Transgenic Mouse Methods and Protocols, second Edition is the ideal guide for all researchers interested in the latest information about the production and analysis of transgenic and knockout mice.

The study of carbonic anhydrase has spanned multiple generations of scientists. Carbonic anhydrase was first discovered in 1932 by Meldrum and Roughton. Inhibition by sulfanilamide was shown in 1940 by Mann and Keilin. Even Hans Krebs contributed to early studies with a paper in 1948 showing the relationship of 25 different sulfonamides to CA inhibition. It was he who pointed out the importance of both the charged and uncharged character of these compounds for physiological experiments. The field of study that focuses on carbonic anhydrase (CA) has exploded in recent years with the identification of new families and isoforms. The CAs are metalloenzymes which are comprised of 5 structurally different families: the alpha, beta, gamma, and delta, and epsilon classes. The alpha class is found primarily in animals with several isoforms associated with human disease. The beta CAs are expressed primarily in plants and are the most divergent. The gamma CAs are the most ancient. These are structurally related to the beta CAs, but have a mechanism more similar to the alpha CAs. The delta CAs are found in marine algae and diflagellates. The epsilon class is found in prokaryotes in which it is part of the carboxysome shell perhaps supplying RuBisCO with CO2 for carbon fixation. With the excitement surrounding the discovery of disease-related CAs, scientists have redoubled their efforts to better understand structure-function relationships, to design high affinity, isotype-specific inhibitors, and to delineate signaling systems that play regulatory roles over expression and activity. We have designed the book to cover basic information of mechanism, structure, and function of the CA families. The authors included in this book bring to light the newest data with regard to the role of CA in physiology and pathology, across phylums, and in unique environmental niches.

The fields of rare diseases research and orphan products development continue to expand with more products in research and development status. In recent years, the role of the patient advocacy groups has evolved into a research partner with the academic research community and the bio-pharmaceutical industry. Unique approaches to research and development require epidemiological data not previously available to assist in protocol study design and patient recruitment for clinical trials required by regulatory agencies prior to approval for access by patents and practicing physicians.

This book discusses a broad range of basic and advanced topics in the field of protein structure, function, folding, flexibility, and dynamics. Starting with a basic introduction to protein purification, estimation, storage, and its effect on the protein structure, function, and dynamics, it also discusses various experimental and computational structure determination approaches; the importance of molecular interactions and water in protein stability, folding and dynamics; kinetic and thermodynamic parameters associated with protein-ligand binding; single molecule techniques and their applications in studying protein folding and aggregation; protein quality control; the role of amino acid sequence in protein aggregation; muscarinic acetylcholine receptors, antimuscarinic drugs, and their clinical significances. Further, the book explains the current understanding on the therapeutic importance of the enzyme dopamine beta hydroxylase; structural dynamics and motions in molecular motors; role of cathepsins in controlling degradation of extracellular matrix during disease states; and the important structure-function relationship of iron-binding proteins, ferritins. Overall, the book is an important guide and a comprehensive resource for understanding protein structure, function, dynamics, and interaction.

The book examines the social and cultural context of new genetic knowledge associated with breast cancer. It looks at how this knowledge and technologies are used and received in two contrasting social arenas - cancer genetic clinics and a breast cancer research charity.

The Short QT Syndrome (SQTS) is characterized by abbreviated QT intervals on the electrocardiogram, increased risk of cardiac arrhythmias and sudden death. Although several gene mutations have been identified in SQT patients, the role of these mutations in promoting arrhythmogenesis is still not completely understood. Consequently, this thesis employs multidisciplinary approaches to develop a 3D virtual heart, which is then used to elucidate how the short QT syndrome facilitates and maintains ventricular arrhythmias and to determine its effects on ventricular mechanical contraction. The findings in this thesis provide a comprehensive and mechanistic explanation for a number of gene mutations associated with potassium channels in terms of susceptibility to arrhythmia. The multiphysics models developed provide a powerful platform for identifying the root causes of various arrhythmias and investigating therapeutic interventions for these diseases.

The thesis was examined by Prof. Chris Huang of the University of Cambridge, the most authoritative figure in cardiac electrophysiology, who has described the work as outstanding. "

The last decades of the past century have brought relentless progress in molecular genetics, opening dramatic opportunities for modifying human life by gene therapy or by cloning new human beings. In this frenzy of new discoveries the names of Cecile and Oskar Vogt, who one hundred years ago envisaged these developments and laid the foundation for modern, genetically oriented neuroscience, have been practically forgotten. This makes most timely the treatise by Igor Klatzo, who spent several years with the Vogts at their Brain Research Institute in the Black Forest, Germany, and then continued his brain research as the Chief of the Laboratory of Neuropathology and Neuroanatomical Sciences at the NIH in Bethesda, MD. Klatzo brings, in addition to the recognition of the Vogts' greatness in pioneering modern brain research, a lively picture of their personalities, which includes their struggles against the rigid rules of society, and political suppression, the latter associated with the risk of their lives.

The present monograph develops a versatile and profound mathematical perspective of the Wright--Fisher model of population genetics. This well-known and intensively studied model carries a rich and beautiful mathematical structure, which is uncovered here in a systematic manner. In addition to approaches by means of analysis, combinatorics and PDE, a geometric perspective is brought in through Amari's and Chentsov's information geometry. This concept allows us to calculate many quantities of interest systematically; likewise, the employed global perspective elucidates the stratification of the model in an unprecedented manner. Furthermore, the links to statistical mechanics and large deviation theory are explored and developed into powerful tools. Altogether, the manuscript provides a solid and broad working basis for graduate students and researchers interested in this field.

Medicine has recently discovered spectacular tools for human enhancement. Yet to date, it has failed to use them well, in part because of ethical objections. Meanwhile, covert attempts flourish to enhance with steroids, mind-enhancing drugs, and cosmetic surgery-all largely unstudied scientifically. The little success to date has been sporadic and financed privately. In How to Build a Better Human, prominent bioethicist Gregory E. Pence argues that people, if we are careful and ethical, can use genetics, biotechnology, and medicine to improve ourselves, and that we should publicly study what people are doing covertly. Pence believes that we need to transcend the two common frame stories of bioethics: bioconservative alarmism and uncritical enthusiasm, and that bioethics should become part of the solution-not the problem-in making better humans.

Bacterial Artificial Chromosomes, Second Edition expands upon the previous edition with current, detailed methods developed for working with BACs. Updated chapters included in this edition present fundamental techniques used for BAC construction and characterization, advanced procedures for introducing modifications, achieving gene expression from BAC vectors, applications of BACs in model organisms, and medical genetics and 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 reproducible laboratory protocols, and tips to troubleshoot and avoid known pitfalls. Authoritative and cutting-edge, Bacterial Artificial Chromosomes, Second Edition seeks to aid scientists in advancing their research using these exciting BAC techniques and strategies.

Stem Cell therapy for lysosomal diseases (LSDs) is developing rapidly. This volume discusses the history, current practice and future perspectives of stem cells in inborn errors of metabolism (IEM) and provides an international perspective on progress, limitations, and future directions (e.g. gene therapy, iPS, ES) in the field. Beginning with an overview of these diseases, the book covers the breadth of this topic from treatment options, bone marrow transplantation, and alternative treatment options, through long-term outcomes and future perspectives.

This detailed volume explores the latest methods that can be used to probe mRNA decay pathways and identify mRNA-binding protein targets as well as miRNA targets. Subjects include metabolic labelling and RNAseq methods for determining RNA decay rates, approaches for discovering RNA-binding protein targets, bioinformatics, miRNA targets and novel components of the miRNA-directed decay pathway, and recently developed approaches for studying nonsense-mediated mRNA decay, among other areas. Written for the highly popular 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. Authoritative and practical, mRNA Decay: Methods and Protocols serves as an ideal guide for molecular biologists, geneticists, and developmental biologists with an interest in understanding how normal development and tissue homeostasis is regulated and how these processes are perturbed in inherited and acquired diseases.