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.

Researchers in the field of ecological genomics aim to determine how a genome or a population of genomes interacts with its environment across ecological and evolutionary timescales. Ecological genomics is trans-disciplinary by nature. Ecologists have turned to genomics to be able to elucidate the mechanistic bases of the biodiversity their research tries to understand. Genomicists have turned to ecology in order to better explain the functional cellular and molecular variation they observed in their model organisms.

We provide an advanced-level book that covers this recent research and proposes future development for this field. A synthesis of the field of ecological genomics emerges from this volume."Ecological Genomics"covers a wide array of organisms (microbes, plants and animals) in order to be able to identify central concepts that motivate and derive from recent investigations in different branches of the tree of life.

"Ecological Genomics"covers 3 fields of research that have most benefited from the recent technological and conceptual developments in the field of ecological genomics: the study of life-history evolution and its impact of genome architectures; the study of the genomic bases of phenotypic plasticity and the study of the genomic bases of adaptation and speciation.

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Pancreatic cancer is a formidable disease, and advances in early detection and improved therapeutics have been slow to come forth. With new advances in molecular genetics in the field of pancreatic tumorigenesis, it is an opportune time to use these recent discoveries to enhance our understanding of pancreatic cancer biology and to improve outcomes in patients. In this volume, leading experts in the field shed light on these findings describing the mutational landscape of pancreatic cancer, including new inroads into our understanding of familial pancreatic cancer, epidemiology, the biology of K-ras signaling, and the emerging contribution of epigenetic alterations to disease initiation and progression. The distinctive pancreatic cancer-stroma ecosystem as determined by the dynamic interplay of inflammation, hallmark mutations, EMT, and cancer stem cells is described, and implications of these interactions in the context of development of novel, personalized therapeutic options are explored.

"BetaSys" uses the example of regulated exocytosis in pancreatic -cells, and its relevance to diabetes, to illustrate the major concepts of systems biology, its methods and applications.

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.

The mechanisms and physiological functions of urea transporters across biological membranes are subjects of long-standing interests. Although urea represents roughly 40% of all urinary solutes in normal human urine, the handling of urea in the tissues has been largely neglected in the past and few clinical or experimental studies now report data on urea. Most recent physiological text books include chapters on water and electrolyte physiology but no chapter on urea. Our aim in writing this book is to stimulate further research in new directions by providing novel and provocative insights into the further mechanisms and physiological significance of urea metabolism and transport in mammals. This book offers a state-of-the-art report on recent discoveries concerning urea transport and where the field is going. It mainly focuses on advances made over the past 20 years on the biophysics, genetics, protein structure, molecular biology, physiology, pathophysiology and pharmacology of urea transport in mammalian cell membranes. It will help graduate students and researchers to get an overall picture of mammalian urea transporters and may also yield benefits for pharmaceutical companies with regard to drug discovery based on the urea transporter. Baoxue Yang is a professor and vice chairman of the Department of Pharmacology, Peking University. He is also an adjunct professor of Jilin University and a visiting professor of Northeast Normal University. Prof. Yang has been researching urea transporters for nearly 20 years and has published more than 70 original research articles in this field.

One of the primary advances for the 21st century is progress beyond the need to defend the findings of behavioral genetic investigations of intelligence. With the advent of developmental behavioral genetics and molecular genetics researchers have taken their discoveries far beyond simple nature/nurture constructs to a finer understanding of how genes and environment intersect to affect cognitive function.

"Behavior Genetics of Cognition across the Lifespan" presents the state of the field in well-documented detail as noted experts examine gene-environment interactions in cognitive function from childhood into old age. Fluidity is at the heart of this coverage: normative and non-normative brain development get equal attention, and statistical, molecular, biological, brain imaging, and neurobiological approaches contribute separately and in combination to the findings.

All major life stages are examined as periods of gene-based cognitive change, including midlife, which until recently has been considered a period for marking time until "real" age-related change occurs. And the book is written so that individual chapters can be as useful on their own as the volume is as a whole. Among the topics covered in depth:

Cognitive abilities in childhood and adolescenceGenetic and environmental influences on intellectual disabilities in childhoodCognition in middle adulthoodGene by environment interplay in cognitive agingDementia: genes, environments, interactionsBrain imaging and cognition

By synthesizing where the field is today--and identifying issues that need further attention--"Behavior Genetics of Cognition across the Lifespan" is a bedrock text for behavioral geneticists, cognitive psychologists and neuroscientists."

Over the past few years, DNA methylation technologies and our knowledge of DNA methylation patterns have been advancing at a breathtaking pace. Due to this fact, DNA Methylation: Methods and Protocols, Second Edition completely revises, updates, and expands upon the popular first edition with the most current novel techniques, easier to use and more refined by the tested experience of leading experts. This revision reflects contemporary study of the subject: the analysis of gene-specific DNA methylation patterns has been complemented by genome-wide approaches, and epigenomics takes a central place. Written in the highly successful Methods in Molecular Biology series format, the chapters in this volume present brief introductions to the topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes which highlight tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, DNA Methylation: Methods and Protocols, Second Edition is the perfect resource for scientists who wish to further our understanding of the molecular processes that determine the genomic DNA methylation landscape and for those who aim to identify and implement DNA methylation-based biomarkers for clinical and diagnostic applications."

High-throughput RNAi screening remains one of the most widely used technologies to perform target identification and validation studies in an unbiased manner. These assays are equally important for research and development across academic, biotech, and pharmaceutical industries. The success of these screening efforts is dependent on robust methodologies to perform these screens. In High-Throughput RNAi Screening: Methods and Protocols, expert researchers in the field share protocols and methods for performing high-throughput RNAi (HT-RNAi) screens. These include the use of various RNAi platforms and delivery methods in mammalian and non-mammalian systems, whole organism and cell models, and various applications, such as drug sensitizer identification. Finally, the book examines the latest advancements in the fields of assay development, library screening, data analysis, and hit selection. 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, High-Throughput RNAi Screening: Methods and Protocols provides a comprehensive source of protocols and other necessary information to make robust and successful assays possible for all who wish to apply HT-RNAi in their research.

Reflecting developments in genome editing, this third edition volume fully updates a collection of key techniques for the study of functional genomics. The book is broken up into sections on bioinformatics, DNA, RNA, and protein analysis, as well as a closing section entitled "From Genotype to Phenotype." 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. Updated and authoritative, Functional Genomics: Methods and Protocols, Third Edition seeks to aid scientists in establishing or extending technologies and techniques in their laboratories.

In most peroxisomal disorders the nervous system is severely affected which explains the clinical and community burden they represent. This is the first book to focus not only on the mutations causing these inherited illnesses, but also on mechanisms that regulate, suppress or enhance expression of genes and their products (enzymes). Indeed since the success and completion of the Human Genome Project all genes (coding DNA sequences) are known. However, of many, their function, and the role of the gene product has not been determined. An example is X-linked adrenoleukodystrophy, the most frequent peroxisomal disorder. Children are born healthy, but in more than 1 out of 3, demyelination of the brain starts unpredictably and they die in a vegetative state. The gene mutated in most families has been known for 10 years; but the true role of the encoded protein, ALDp, is still speculative; and within the same family, very severe and asymptomatic clinical histories co-exist, unexplained by the mutation.

This book is unique in covering a wide range of design and analysis issues in genetic studies of rare variants, taking advantage of collaboration of the editors with many experts in the field through large-scale international consortia including the UK10K Project, GO-T2D and T2D-GENES. Chapters provide details of state-of-the-art methodology for rare variant detection and calling, imputation and analysis in samples of unrelated individuals and families. The book also covers analytical issues associated with the study of rare variants, such as the impact of fine-scale population structure, and with combining information on rare variants across studies in a meta-analysis framework. Genetic association studies have in the last few years substantially enhanced our understanding of factors underlying traits of high medical importance, such as body mass index, lipid levels, blood pressure and many others. There is growing empirical evidence that low-frequency and rare variants play an important role in complex human phenotypes. This book covers multiple aspects of study design, analysis and interpretation for complex trait studies focusing on rare sequence variation. In many areas of genomic research, including complex trait association studies, technology is in danger of outstripping our capacity to analyse and interpret the vast amounts of data generated. The field of statistical genetics in the whole-genome sequencing era is still in its infancy, but powerful methods to analyse the aggregation of low-frequency and rare variants are now starting to emerge. The chapter Functional Annotation of Rare Genetic Variants is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

The Ontogeny of Human Bonding Systems takes an interdisciplinary look at the phenomena of human bonding. The authors draw upon behavioral genetics, molecular genetics of behavior, cognitive and affective neuroscience, evolutionary psychology, human ethology, behavioral ecology, and the study of attachment processes within developmental psychology. The topics will emphasize human reproduction, and fertility-related behavior in particular, and the evolutionary origins and neural underpinnings of such behavior. This book is for anyone interested in the evolutionary origins, neural underpinnings, and psychological structure involved in human relationships.

This volume provides a cross-section of RNA exosome research protocols, applied to a diversity of model organisms. Chapters guide readers through methods that e.g. delineate eukaryotic exosomes' origins in prokaryotes, probe its RNA substrates, adapter complexes and macromolecular interaction of networks, and establish critical structural-function relationships. 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, The Eukaryotic RNA Exosome: Methods and Protocols aims to ensure successful results in the further study of this vital field.

This book describes important developments and emerging trends in experimental and clinical cancer gene therapy. It reflects the tremendous advances made over recent years with respect to immunogenes, suicide genes and gene correction therapies, as well as in gene suppression and miRNA therapies. Many of the described strategies focus on the generation of more efficient and specific means of attack at known and novel cellular targets associated with tumor development and progression. The book also details parallel improvements in vector design, vector delivery, and therapeutic efficacy. It offers readers a stimulating, broad overview of advances in the field, linking experimental strategies to their clinical applications.

Researchers seeking problems that offer more hope of success often avoid subjects that seem to be difficult to approach experimentally, or subjects for which experimental results are difficult to interpret. The breakdown part of protein turnover in vivo, particularly in nervous tissue, was such a subject in the past - it was difficult to measure and difficult to explore the mechanisms involved. For factors that influence protein metabolism, it was thought that protein content, function, and distribution are controlled only by the synthetic mechanisms that can supply the needed specificity and response to stimuli. The role of breakdown was thought to be only a general metabolic digestion, elimination of excess polypeptides. We now know that the role of breakdown is much more complex: it has multiple functions, it is coupled to turnover, and it can affect protein composition, function, and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions: it serves to activate and inactivate enzymes, modulate membrane function, alter receptor channel properties, affect transcription and cell cycle, form active peptides, and much more. The hydrolysis of peptide bonds often involves multiple steps, many enzymes, and cycles (such as ubiquination), and often requires the activity of enzyme complexes. Their activation, modification, and inactivation can thus play an important role in biological functions, with numerous families of proteases participating. The specific role of each remains to be elucidated.

The discovery of wide-spread RNA-based regulation in bacteria has led to new evaluations of the importance of bacterial regulatory RNA in every aspect of bacterial physiology. In Bacteria Regulatory RNA: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study bacterial regulatory RNA. These include methods and techniques to identify regulatory RNAs, characterizing the function and expression of regulatory RNAs in bacterial cells, RNA structure prediction, and interactions between regulatory RNAs and proteins. 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 practical, Bacteria Regulatory RNA: Methods and Protocols seeks to aid scientists in the further study of bacterial regulatory RNA.

This volume provides an interdisciplinary perspective of applying Next Generation Sequencing (NGS) technology to cancer research. It aims to systematically introduce the concept of NGS, a variety of NGS platforms and their practical implications in cancer biology.This unique and comprehensive text will integrate the unprecedented NGS technology into various cancer research projects as opposed to most books which offer a detailed description of the technology. This volume will present true experimental results with concrete data processing pipelines, discuss the bottleneck of each platform for real project in cancer research. In additional, single cancer cell sequencing as the proof of concept will be introduced in this book, along with cutting-edge information provided will help the intended audience to develop a comprehensive understanding of the NGS technology and practical whole genome sequencing data analysis and rapidly translate into their own research, specifically in the field of cancer biology.

Should parents aim to make their children as normal as possible to increase their chances to "fit in"? Are neurological and mental health conditions a part of children's identity and if so, should parents aim to remove or treat these? Should they aim to instill self-control in their children? Should prospective parents take steps to insure that, of all the children they could have, they choose the ones with the best likely start in life? This volume explores all of these questions and more. Against the background of recent findings and expected advances in neuroscience and genetics, the extent and limits of parental responsibility are increasingly unclear. Awareness of the effects of parental choices on children's wellbeing, as well as evolving norms about the moral status of children, have further increased expectations from (prospective) parents to take up and act on their changing responsibilities. The contributors discuss conceptual issues such as the meaning and sources of moral responsibility, normality, treatment, and identity. They also explore more practical issues such as how responsibility for children is practiced in Yoruba culture in Nigeria or how parents and health professionals in Belgium perceive the dilemmas generated by prenatal diagnosis.

This volume provides a comprehensive overview of the experimental and computational methodologies used to study the function of long non-coding RNA (ncRNAs) expressed from enhancers. Chapter detail both wet-lab and dry-lab techniques and annotating long ncRNAs and exploring transcription by assessing where transcription starts and generally how it occurs.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, Enhancer RNAs: Methods and Protocols aims to ensure successful results in this rapidly developing field.

This book presents the statistical aspects of designing, analyzing and interpreting the results of genome-wide association scans (GWAS studies) for genetic causes of disease using unrelated subjects. Particular detail is given to the practical aspects of employing the bioinformatics and data handling methods necessary to prepare data for statistical analysis. The goal in writing this book is to give statisticians, epidemiologists, and students in these fields the tools to design a powerful genome-wide study based on current technology. The other part of this is showing readers how to conduct analysis of the created study.

Design and Analysis of Genome-Wide Association Studies provides a compendium of well-established statistical methods based upon single SNP associations. It also provides an introduction to more advanced statistical methods and issues. Knowing that technology, for instance large scale SNP arrays, is quickly changing, this text has significant lessons for future use with sequencing data. Emphasis on statistical concepts that apply to the problem of finding disease associations irrespective of the technology ensures its future applications. The author includes current bioinformatics tools while outlining the tools that will be required for use with extensive databases from future large scale sequencing projects. The author includes current bioinformatics tools while outlining additional issues and needs arising from the extensive databases from future large scale sequencing projects.

Annual Reports in Medicinal Chemistry provides timely and critical reviews of important topics in medicinal chemistry together with an emphasis on emerging topics in the biological sciences, which are expected to provide the basis for entirely new future therapies.

Part of the "Studies in Biology, Economy and Society" series, this book looks at Sir Francis Galton (1822-1911), a grandson of Erasmus Darwin. In his twenties he won fame as an explorer, writing "The Art of Travel", and was on the council of the Geographical Society for many years. He worked at the prediction of weather, and described his discovery of the anticyclone to the Royal Society in 1862 and in "Meteorographica" (1863). He first became an anthropologist in 1862 when he joined the Ethnological Society, which emerged to become the Anthropological Institute in 1871 - Galton was president from 1885 to 1889. He initiated anthropometry and the measurement of human variation, and the use of photography for the analysis of differences, or individual characteristics, in a group. He recognized the uniqueness of "Finger Prints" (1893), and, in 1875, first used the records of pairs of identical twins in his research into the laws of heredity. It was on the publication of the "Origin of the Species" by his cousin Charles that he realized the importance of inheritance and the transmission of characters of body and brain from parent to child. His "Hereditary Genius" came out in 1869, "Inq

Chemical genomics technology has been steadily improving, delivering new biological probes and drugs, and the explicit use of the term 'chemical proteomics' has increased with it, as proteins have always been at the heart of this technology. In "Chemical Genomics and Proteomics: Reviews and Protocols," experts in the field present updated reviews of the chemistry of small molecules and their interaction with protein targets as well as detailed protocols that cover different types of ligands, carbohydrates, and lipids. For example, the generation of their protein targets and methods for measuring their interactions is covered. Written in the highly successful "Methods in Molecular Biology " series format, methodology 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.

Thorough and up to date, "Chemical Genomics and Proteomics: Reviews and Protocols" aims to provide inspiration to those who wish to use chemical genomics and proteomics in their work and develop this young field into full maturity through the incorporation of the new biological and chemical technologies beginning to emerge here."