ThediscoveryofmicroRNAshasrevealedanunexpectedandspectacularadditional levelof?netuningofthegenomeandhowgenesareusedagainandagainin differentcombinationstogeneratethecomplexitythatunderliesforinstancethe brain. SincetheinitialstudiesperformedinC. elegans,wegavegoneafarwayto begintounderstandhowmicroRNApathwayscanhaveanimpactonhealthand diseaseinhuman. AlthoughmicroRNAsareabundantlyexpressedinthebrain, relativelylittleisknownaboutthemultiplefunctionsoftheseRNAmoleculesinthe nervous system. Nevertheless,we knowalready that microRNA pathways play majorrolesintheproliferation,differentiation,functionandmaintenanceofneu- nalcells. SeveralintriguingstudieshavelinkedmicroRNAsasmajorregulatorsof theneuronalphenotype,andhaveimplicatedspeci?cmicroRNAsintheregulation ofsynapseformationandplasticity. DysfunctionofmicroRNApathwaysisalso slowlyemergingasapotentialimportantcontributortothepathogenesisofmajor neurodegenerativedisorderssuchasAlzheimer'sdiseaseandParkinson'sdisease. Thesenovelinsightsappeartobeparticularpromisingfortheunderstandingofthe veryfrequentandbadlyunderstoodsporadicformsofthesediseasesascomparedto thegeneticforms. Thus,thebetterunderstandingoftheimplicationsofthisnovel ?eldofmolecularbiologyiscrucialforthebroadareaofneurosciences,fromthe fundamentalaspectstotheclinic,andfromnoveldiagnostictopotentiallythe- peuticapplicationsforsevereneurologicalandmaybepsychiatricdiseases. The presentvolumegatherscontributionstotheColloqueMe'decineetRechercheonthe implicationsofmicroRNAsinneuroscienceorganizedbytheFondationIpsen,in Paris,onApril20,2009. Ithadasobjectivetobringtogetherneuroscientistsfrom differentareasofresearchtodiscusstheircurrentinsightsintothewonderfulworld ofmicroRNAs,andtohearanddiscusstheirresearchandviewsaboutmicroRNA biologyinneuronalprocessesandinbraindisorders. BartdeStrooper YvesChristen v Acknowledgments The editors wish to thank Jacqueline Mervaillie and Sonia Le Cornec for the organizationofthemeetingandMaryLynnGagefortheeditingofthebook. vii Contents Pro?lingthemicroRNAs ...1 KennethS. Kosik,ThalesPapagiannakopoulos,NaXu, KawtherAbu-Elneel,TsunglinLiu,andMinJeongKye TheWideVarietyofmiRNAExpressionPro?les intheDevelopingandMatureCNS ...9 MarikaKapsimali InteractionsbetweenmicroRNAsandTranscription FactorsintheDevelopmentandFunction oftheNervousSystem ...19 DavidJ. Simon AmicroRNAFeedbackCircuitinMidbrainDopamineNeurons ...27 AsaAbeliovich Fine-tuningmRNATranslationatSynapseswithmicroRNAs ...35 GerhardM. Schratt NeuronalP-bodiesandTransportofmicroRNA-Repressed mRNAs ...4 5 FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation inStemCells ...57 KeithSzulwach,ShuangChang,andPengJin microRNAsinCNSDevelopmentandNeurodegeneration: InsightsfromDrosophilaGenetics ...69 StephenM. Cohen ix x Contents DrosophilaasaModelforNeurodegenerativeDisease: RolesofRNAPathwaysinPathogenesis ...79 NancyM. Bonini microRNAsinSporadicAlzheimer'ThediscoveryofmicroRNAshasrevealedanunexpectedandspectacularadditional levelof?netuningofthegenomeandhowgenesareusedagainandagainin differentcombinationstogeneratethecomplexitythatunderliesforinstancethe brain. SincetheinitialstudiesperformedinC. elegans,wegavegoneafarwayto begintounderstandhowmicroRNApathwayscanhaveanimpactonhealthand diseaseinhuman. AlthoughmicroRNAsareabundantlyexpressedinthebrain, relativelylittleisknownaboutthemultiplefunctionsoftheseRNAmoleculesinthe nervous system. Nevertheless,we knowalready that microRNA pathways play majorrolesintheproliferation,differentiation,functionandmaintenanceofneu- nalcells. SeveralintriguingstudieshavelinkedmicroRNAsasmajorregulatorsof theneuronalphenotype,andhaveimplicatedspeci?cmicroRNAsintheregulation ofsynapseformationandplasticity. DysfunctionofmicroRNApathwaysisalso slowlyemergingasapotentialimportantcontributortothepathogenesisofmajor neurodegenerativedisorderssuchasAlzheimer'sdiseaseandParkinson'sdisease. Thesenovelinsightsappeartobeparticularpromisingfortheunderstandingofthe veryfrequentandbadlyunderstoodsporadicformsofthesediseasesascomparedto thegeneticforms. Thus,thebetterunderstandingoftheimplicationsofthisnovel ?eldofmolecularbiologyiscrucialforthebroadareaofneurosciences,fromthe fundamentalaspectstotheclinic,andfromnoveldiagnostictopotentiallythe- peuticapplicationsforsevereneurologicalandmaybepsychiatricdiseases. The presentvolumegatherscontributionstotheColloqueMe'decineetRechercheonthe implicationsofmicroRNAsinneuroscienceorganizedbytheFondationIpsen,in Paris,onApril20,2009. Ithadasobjectivetobringtogetherneuroscientistsfrom differentareasofresearchtodiscusstheircurrentinsightsintothewonderfulworld ofmicroRNAs,andtohearanddiscusstheirresearchandviewsaboutmicroRNA biologyinneuronalprocessesandinbraindisorders. BartdeStrooper YvesChristen v Acknowledgments The editors wish to thank Jacqueline Mervaillie and Sonia Le Cornec for the organizationofthemeetingandMaryLynnGagefortheeditingofthebook. vii Contents Pro? lingthemicroRNAs ...1 KennethS. Kosik,ThalesPapagiannakopoulos,NaXu, KawtherAbu-Elneel,TsunglinLiu,andMinJeongKye TheWideVarietyofmiRNAExpressionPro?les intheDevelopingandMatureCNS ...9 MarikaKapsimali InteractionsbetweenmicroRNAsandTranscription FactorsintheDevelopmentandFunction oftheNervousSystem ...19 DavidJ. Simon AmicroRNAFeedbackCircuitinMidbrainDopamineNeurons ...27 AsaAbeliovich Fine-tuningmRNATranslationatSynapseswithmicroRNAs ...35 GerhardM. Schratt NeuronalP-bodiesandTransportofmicroRNA-Repressed mRNAs ...45 FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation inStemCells ...57 KeithSzulwach,ShuangChang,andPengJin microRNAsinCNSDevelopmentandNeurodegeneration: InsightsfromDrosophilaGenetics ...69 StephenM. Cohen ix x Contents DrosophilaasaModelforNeurodegenerativeDisease: RolesofRNAPathwaysinPathogenesis ...79 NancyM. Bonini microRNAsinSporadicAlzheimer'sDiseaseandRelated Dementias ...91 Se'bastienS. He'bert,WimMandemakers,AikateriniS. Papadopoulou, andBartDeStrooper microRNADysregulationinPsychiatricDisorders ...99 BinXu,JosephA. Gogos,andMariaKarayiorgou Index ...1 19 Contributors Abeliovich Asa Columbia University Medical Center, 630 West 168th Street, Room15-405,NewYork,NY10032,USA,aa900@columbia. edu Abu-ElneelKawther NeuroscienceResearchInstitute,DepartmentofMolecular CellularandDevelopmentalBiology,UniversityofCaliforniaSantaBarbara,USA BoniniNancyM. UniversityofPennsylvania,306LeidyLaboratories,Depa- mentofBiology,Philadelphia,PA19104,USA,nbonini@sas. upenn. edu Chang Shuang Department of Human Genetics, Emory University School of Medicine,Atlanta,GA30322,USA CohenStephenM. TemasekLifeSciencesLaboratoryLimited,1ResearchLink National University of Singapore, 117604 Singapore, SINGAPORE, steve@ tll. org. sg DeStrooperBart Centerforhumangenetics,K. U. LeuvenandDepartmentof molecularanddevelopmentalgenetics,VIBLeuven,BELGIUM GogosJosephA. DepartmentofPhysiology&CellularBiophysicsandDepa- mentofNeuroscience,ColumbiaUniversity,NewYork,USA He'bert Se'bastien S. Centre de Recherche du CHUQ (CHUL), Axe Neur- ciences,Universite'Laval,De'partementdeBiologieme'dicale,2705Boul. Laurier, LocalRC-9800,Que'bec,Qc,Canada,sebastien. hebert@crchul. ulaval. ca JinPeng DepartmentofHumanGeneticsandGraduatePrograminGeneticsand MolecularBiology,EmoryUniversitySchoolofMedicine,Atlanta,GA30322, USA,pjin@genetics. emory. edu ' ' ' ' KapsimaliMarika INSERMU784,GenetiqueMoleculaireduDeveloppement, ' Ecole Normale Superieure, 46 rue d'Ulm, 75230 PARIS Cedex 05 FRANCE, kapsimal@biologie. ens. fr xi xii Contributors Karayiorgou Maria Columbia University, Department of Psychiatry, 1051 RiversideDrive,Unit#28,NewYorkNY10032,USA,mk2758@columbia. edu Kosik Kenneth S. Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, University of California Santa Barbara, BiologyII,Room6139A,SantaBarbara,CA93106,USA,kosik@lifesci. ucsb.

The Human Genome Diversity Project (HGDP) was launched in 1991 by a group of population geneticists whose aim was to map genetic diversity in hundreds of human populations by tracing the similarities and differences between them. It quickly became controversial and was accused of racism and 'bad science' because of the special interest paid to sampling cell material from isolated and indigenous populations. The author spent a year carrying out participant observation in two of the laboratories involved and provides fascinating insights into daily routines and technologies used in those laboratories and also into issues of normativity, standardization and naturalisation. Drawing on debates and theoretical perspectives from across the social sciences, M'charek explores the relationship between the tools used to produce knowledge and the knowledge thus produced in a way that illuminates the HGDP but also contributes to our broader understanding of the contemporary life sciences and their social implications.

The Human Genome Diversity Project (HGDP) was launched in 1991 by a group of population geneticists whose aim was to map genetic diversity in hundreds of human populations by tracing the similarities and differences between them. It quickly became controversial and was accused of racism and 'bad science' because of the special interest paid to sampling cell material from isolated and indigenous populations. The author spent a year carrying out participant observation in two of the laboratories involved and provides fascinating insights into daily routines and technologies used in those laboratories and also into issues of normativity, standardization and naturalisation. Drawing on debates and theoretical perspectives from across the social sciences, M'charek explores the relationship between the tools used to produce knowledge and the knowledge thus produced in a way that illuminates the HGDP but also contributes to our broader understanding of the contemporary life sciences and their social implications.

Do real stem cells and stem cell lineages exist in lower organisms? Can stem cells from one organism parasitize the soma and/or the germ line of conspecifics? Can differentiated cells in marine organisms be re-programmed to regenerate tissues, organs and appendages through novel de-differentiation, transdifferentiation, or re-differentiation processes, leading to virtually all three germ layers, including the germline? The positive answers to above questions open a new avenue in stem cell research: the biology of stem cells in marine organisms. It is therefore unfortunate that while the literature on stem cell from terrestrial organisms is rich and expanding at an exponential rate, investigations on marine organisms stem cells are very limited and scarce.

By presenting theoretical chapters, overview essays and specific research results, this book summarises the knowledge and the hypotheses on stem cells in marine organisms through major phyla and specific model organisms. The study on stem cells from marine invertebrates may shed lights on mechanisms promoting immunity, developmental biology, regeneration and budding processes in marine invertebrates, body maintenance, aging and senescence. It aims in encouraging a larger scientific community to follow and study the novel phenomena of stem cells behaviours as depicted from the few currently studied marine invertebrates.

This book outlines comprehensive information on the global trends, policies, research priorities and frontier innovations made in the research domain of breeding, biotechnology, biofortification and quality enhancement of wheat and barley. With contributions by international group of leading wheat and barley researchers, this book offers data-based insights along with a holistic view of the subject and serve as a vital resource of information for scientists engaged in breeding future high-yielding biofortified varieties. It catalogs both conventional as well as modern tools for gene identification and genome editing interventions for enhancing the yield, grain quality, disease and pest resistance, nutrient-use efficiency and abiotic stress tolerance. The prospects of processing high quality wheat end-products with long term storage and high nutritional quality are also discussed. This book is of interest to teachers, researchers, molecular breeders, cereal biochemists and biotechnologist, policymakers and professionals working in the area of wheat and barley research, food and cereal industry. Also, the book serves as an additional reading material for the undergraduate and graduate students of agriculture and food sciences. National and international agricultural scientists, policy makers will also find this book to be a useful read. Volume 2 of New Horizons in Wheat and Barley Research covers topics in crop protection and resource management.

Collected for the first time in a single volume are essays which examine the developments in three fundamental biological disciplines - embryology, evolutionary biology, and genetics. These disciplines were in conflict for much of the twentieth century and the essays in this collection examine key methodological problems within these disciplines and the difficulties faced in overcoming the conflicts between them. Burian skilfully weaves together historical appreciation of the settings within which scientists work, substantial knowledge of the biological problems at stake and the methodological and philosophical issues faced in integrating biological knowledge drawn from disparate sources. The final chapter describes what recent findings in development biology and genetics can tell us about the history and development of animals. Written in a clear, accessible style this collection should appeal to students and professionals in philosophy of science, and the philosophy and history of biology.

Collected for the first time in a single volume are essays which examine the developments in three fundamental biological disciplines - embryology, evolutionary biology, and genetics. These disciplines were in conflict for much of the twentieth century and the essays in this collection examine key methodological problems within these disciplines and the difficulties faced in overcoming the conflicts between them. Burian skilfully weaves together historical appreciation of the settings within which scientists work, substantial knowledge of the biological problems at stake and the methodological and philosophical issues faced in integrating biological knowledge drawn from disparate sources. The final chapter describes what recent findings in development biology and genetics can tell us about the history and development of animals. Written in a clear, accessible style this collection should appeal to students and professionals in philosophy of science, and the philosophy and history of biology.

Bioinformatics is a relatively new field of research. It evolved from the requirement to process, characterize, and apply the information being produced by DNA sequencing technology. The production of DNA sequence data continues to grow exponentially. At the same time, improved bioinformatics such as faster DNA sequence search methods have been combined with increasingly powerful computer systems to process this information. Methods are being developed for the ever more detailed quantification of gene expression, providing an insight into the function of the newly discovered genes, while molecular genetic tools provide a link between these genes and heritable traits. Genetic tests are now available to determine the likelihood of suffering specific ailments and can predict how plant cultivars may respond to the environment. The steps in the translation of the genetic blueprint to the observed phenotype is being increasingly understood through proteome, metabolome and phenome analysis, all underpinned by advances in bioinformatics. Bioinformatics is becoming increasingly central to the study of biology, and a day at a computer can often save a year or more in the laboratory.

The volume is intended for graduate-level biology students as well as researchers who wish to gain a better understanding of applied bioinformatics and who wish to use bioinformatics technologies to assist in their research. The volume would also be of value to bioinformatics developers, particularly those from a computing background, who would like to understand the application of computational tools for biological research. Each chapter would include a comprehensive introduction giving an overview of the fundamentals, aimed at introducing graduate students and researchers from diverse backgrounds to the field and bring them up-to-date on the current state of knowledge. To accommodate the broad range of topics in applied bioinformatics, chapters have been grouped into themes: gene and genome analysis, molecular genetic analysis, gene expression analysis, protein and proteome analysis, metabolome analysis, phenome data analysis, literature mining and bioinformatics tool development. Each chapter and theme provides an introduction to the biology behind the data describes the requirements for data processing and details some of the methods applied to the data to enhance biological understanding.

What are the agents of life? Central to our conception of the biological world is the idea that it contains various kinds of individuals, including genes, organisms, and species. How we conceive of these agents of life is central to our understanding of the relationship between life and mind, the place of hierarchical thinking in the biological sciences, and pluralistic views of biological agency. Genes and the Agents of Life rethinks the place of the individual in the biological sciences, drawing parallels with the cognitive and social sciences. Genes, organisms, and species are all agents of life, but how are each of these conceptualized within genetics, developmental biology, evolutionary biology, and systematics? The book includes highly accessible discussions of genetic encoding, species and natural kinds, and pluralism above the levels of selection, drawing on work from across the biological sciences. A companion to Boundaries of the Mind, (Cambridge, 2004) where the focus is on the cognitive sciences, this volume will appeal to professionals and students in philosophy, biology, and the history of science. Robert A. Wilson is Professor of Philosophy at the University of Alberta. He is the author of Cartesian Psychology and Physical Minds (Cambridge, 1995).

The development of gene-based technologies has been rapid over the past decade and has consequently resulted in a surge of interest in human gene therapy, the deliberate transfer of genes to somatic cells to cure or alleviate disease symptoms.
Hundreds of clinical protocols involving variously designed vectors for efficient gene transfer have been developed. However, the use of such complex 'gene medicines'’ containing potentially heritable genes has raised numerous concerns regarding quality, efficacy and safety.
Encompassing recent developments in the field and addressing current concerns this book:

• surveys many of the current technologies for preparing vectors for use in gene therapy protocols
• reviews the application of gene-mediated therapies to a range of medical conditions
• considers the regulatory aspects of gene therapy including product quality and safety requirements
• appraises the transfer of technologies from laboratory to clinic with regard to the attendant requirements and facilities for:
• good laboratory practice (GLP) conditions in the R&D laboratory
• large-scale production methods and good manufacturing practice (GMP)
• current in-process and final product testing

Written by international experts knowledgeable about many aspects of human somatic gene therapy, this book will be an essential guide for those embarking on gene therapy technologies relevant to specifications of production and testing of products (and procedures) required to meet existing regulations, including quality, efficacy and safety considerations.

Adult neurogenesis has been questioned for many years. In the early 1900s, a dogma was established that denied new neuron formation in the adult brain. In the last century however, new discoveries have demonstrated the real existence of proliferation in the adult brain, and in the last decade, these studies led to the identification of neural stem cells in mammals. Adult neural stem cells are undifferentiated cells that are present in the adult brain and are capable of dividing and differentiating into glia and new neurons. Newly formed neurons terminally differentiate into mature neurons in the olfactory bulb and the dentate gyrus of the hippocampus. Since then, a number of new research lines have emerged whose common objective is the phenotypical and molecular characterization of brain stem cells. As a result, new therapies are successfully being applied to animal models for certain neurodegenerative diseases or stroke. At present, and in years to come, this finding extends to the adult human brain, and gives reason and hope to all the previous studies.

Statistical genetics has become a core course in many graduate programs in public health and medicine. This book presents fundamental concepts and principles in this emerging field at a level that is accessible to students and researchers with a first course in biostatistics. Extensive examples are provided using publicly available data and the open source, statistical computing environment, R.

Historically, philosophers of biology have tended to sidestep the problem of development by focusing primarily on evolutionary biology and, more recently, on molecular biology and genetics. Quite often too, development has been misunderstood as simply, or even primarily, a matter of gene activation and regulation. Nowadays a growing number of philosophers of science are focusing their analyses on the complexities of development, and in Embryology, Epigenesis and Evolution Jason Scott Robert explores the nature of development against current trends in biological theory and practice and looks at the interrelations between development and evolution (evo-devo), an area of resurgent biological interest. Clearly written, this book should be of interest to students and professionals in the philosophy of science and the philosophy of biology.

This collection of essays considers the foundation and historical development of population biology and its relationship to population genetics and population ecology. It also considers its relationship to the rapidly growing fields of molecular quantitative genetics, genomics and bioinformatics. Although set in historical context, the volume's up-to-date coverage of relevant material reveals the central role of population biology in all aspects of its connection to population genetics and population ecology.

Nature has long used nucleic acid aptamers and enzymes for regulatory activities, such as the recently discovered riboswitches involved in gene expression. The existence of a large array of natural and artificial functional nucleic acids has generated tremendous enthusiasm and new opportunities for molecular scientists from diverse disciplines to devise new concepts and real applications that take advantage of those nucleic acids for sensing and other analytical applications. This book provides a timely and comprehensive overview of recent advances in the field, from leading experts in biology, chemistry, and engineering. A variety of topics are covered, from fundamentals of functional nucleic acids, to their applications as sensors, to nanotechnologies; as well as integration of functional nucleic acids into practical analytical systems.

An accurate description of current scientific developments in the field of bioinformatics and computational implementation is presented by research of the BioSapiens Network of Excellence. Bioinformatics is essential for annotating the structure and function of genes, proteins and the analysis of complete genomes and to molecular biology and biochemistry.

Included is an overview of bioinformatics, the full spectrum of genome annotation approaches including; genome analysis and gene prediction, gene regulation analysis and expression, genome variation and QTL analysis, large scale protein annotation of function and structure, annotation and prediction of protein interactions, and the organization and annotation of molecular networks and biochemical pathways. Also covered is a technical framework to organize and represent genome data using the DAS technology and work in the annotation of two large genomic sets: HIV/HCV viral genomes and splicing alternatives potentially encoded in 1% of the human genome.

Due to the vital biological importance of RNA and proteins functioning together within a cell, a protocol volume describing experimental procedures to study their interactions should find a home in many laboratories. RNA-Protein Interaction Protocols, Second Edition updates, complements, and expands upon the popular first edition by providing a collection of cutting-edge techniques developed or refined in the past few years along with tried-and-true methods. The expert contributors explore the isolation and characterization of RNA-protein complexes, the analysis and measurement of RNA-protein interaction, and related novel techniques and strategies. Written in the highly successful Methods in Molecular Biologya"[ series format, the chapters include brief introductions to the material, lists of necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and a Notes section which highlights tips on troubleshooting and avoiding known pitfalls.

Comprehensive and up-to-date, RNA-Protein Interaction Protocols, Second Edition is an ideal guide for researchers continuing the study of this all-important biological partnership.

Insect pests remain one of the main constraints to food and fiber production worldwide despite farmers deploying a range of techniques to protect their crops. Modern pest control is guided by the principles of integrated pest management (IPM) with pest resistant germplasm being an important part of the foundation. Since 1996, when the first genetically modified (GM) insect-resistant maize variety was commercialized in the USA, the area planted to insect-resistant GM varieties has grown dramatically, representing the fastest adoption rate of any agricultural technology in human history. The goal of our book is to provide an overview on the role insect-resistant GM plants play in different crop systems worldwide. We hope that the book will contribute to a more rational debate about the role GM crops can play in IPM for food and fiber production.

Anomalous epigenetic patterns touch many areas of study including biomedical, scientific, and industrial. With perspectives from international experts, this resource offers an all-inclusive overview of epigenetics, which bridge DNA information and function by regulating gene expression without modifying the DNA sequence itself. Epigenetics, in its most basic form, means heredity is not the sole determining factor in disease development. Rather, environmental and dietary factors can trigger a gene to behave in an unintended way, while the gene itself remains unchanged. Epigenetics in Biology and Medicinediscusses cell biology and epigenetics' role in human, animal, and plant diseases, including distortions in DNA methylation. The text also covers histone modifications, and epigenomics, as well as dietary and environmental impacts on epigenetic changes. Addresses These Important Questions: How promising are HDACi drugs as anti-tumor agents? Will restoring normal levels of miRNAs change the course of devastating diseases? Is it possible to alter epigenetic mechanisms once they are triggered? Is it possible to correct the abnormalities in methylation patterns that impact auto-immunities? Represents a Landmark Publication in this Cutting-Edge Field Dr. Manel Esteller, the editor of the volume, is a leading expert in molecular genetics of endometrial carcinoma. Under his editorial guidance, this publication goes beyond heredity to explain the crucial role of epigenetics in plants and physical and psychological diseases. This text is applicable to a wide range of researchers, including those invested in the applications of cell biology, those involved in disease research and deciding genetic patterns, and those coalitions concerned with the impact of epigenetics and possible cures. As a result, it has the potenti

This unique book is concerned with the general principles and theories of population ecology, based on the idea that the rules governing the dynamics of populations are relatively simple, and that the rich behavior we observe in nature is a consequence of the structure of the system rather than of the complexity of the underlying rules. From this perspective, the dynamic behavior of single-species populations is examined and an elementary feedback model of the population system is developed. This single-species model is refined and generalized by examining the mechanisms of population regulation.

RNA interference (RNAi), in which RNA silences RNA, is the most recent discovery to revolutionize the study of biology. In RNAi: Design and Applications, leaders in the field contribute state-of-the-art, easy to follow methods and bench protocols designed for practical, everyday use of RNAi in biological research. Divided into two parts, this comprehensive volume covers fundamentals including designs of RNAi, biochemical assay protocols for the major components of RNAi, and study of potential off-target effects, followed by an extensive section covering various applications of RNAi in diverse model organisms and systems, from antiviral and anticancer applications to altering flower color in plants. Cutting edge and clearly written, RNAi: Design and Applications enables a researcher with standard molecular biological training to perform major RNAi-related experiments and contribute to this revolutionary, growing field.

Kary Mullis was awarded a Nobel Prize for inventing the PCR technique more than 15 years ago in 1993. Since its "discovery," multiple adaptations and variations of the standard PCR technique have been described, with many of these adaptations and variations currently being used in clinical, diagnostic and academic laboratories across the world. Further, these techniques are being applied at the diagnostic level (e.g. as high throughput testing methodologies to detect minimum residual disease, the presence/absence of specific pathogens etc), as well as to increase our understanding of fundamental disease processes.

Frequently, PCR technicians and specialists limit their understanding of PCR to one particular methodology. However, this approach limits their appreciation of the range of versatile PCR techniques currently available, techniques that may be applicable and indeed more suitable to their own laboratory situation.

This manual aims to provide the reader with a guide to the standard PCR technique and its many available modifications, with particular emphasis on the role of PCR techniques in the diagnostic laboratory (the central theme of this manual). Further, many important technical issues have been addressed, including types of PCR template material, PCR optimization, the analysis of PCR products, quality control and quality assurance, variants and adaptations of the standard PCR protocol, quantitative PCR and in situ PCR. The reader of this manual will be excellently informed about the fundamental principles of PCR and the true potential of PCR within clinical laboratory practice.

In 1901 William Bateson, Professor of Biology at Cambridge, published a renewed version of a lecture which he had delivered the year before to the Royal Horticultural Society in London (reprinted in the book as an appendix). In this lecture he recognized the importance of the work completed by Gregor Mendel in 1865, and brought it to the notice of the scientific world. Upon reading Bateson's paper, Archibald Garrod realized the relevance of Mendel's laws to human disease and in 1902 introduced Mendelism to medical genetics. The first part of A Century of Mendelism in Human Genetics takes a historical perspective of the first 50 years of Mendelism, including the bitter argument between the Mendelians and the biometricians. The second part discusses human genetics since 1950, ending with a final chapter examining genetics and the future of medicine. The book considers the genetics of both single-gene and complex diseases, human cancer genetics, genetic linkage, and natural selection in human populations. Besides being of general medical significance, this book will be of particular interest to departments of genetics and of medical genetics, as well as to historians of science and medicine.

Reshaping Life is an eminently authoritative and lucid description of modern molecular biology and genetics, and the ethical implications of genetic engineering. Now in its third edition, it is fully revised and updated, taking advantage of a decade of progress in genetics and biotechnology. It offers a concise working knowledge of DNA science and of those aspects of cell biology needed to understand such issues as animal cloning, genetically modified food, and gene therapy. It examines the debates on the sociological and ethical issues surrounding modern technology, laying out the issues for the reader, while urging a rational approach.

Reshaping Life is an eminently authoritative and lucid description of modern molecular biology and genetics, and the ethical implications of genetic engineering. Now in its third edition, it is fully revised and updated, taking advantage of a decade of progress in genetics and biotechnology. It offers a concise working knowledge of DNA science and of those aspects of cell biology needed to understand such issues as animal cloning, genetically modified food, and gene therapy. It examines the debates on the sociological and ethical issues surrounding modern technology, laying out the issues for the reader, while urging a rational approach.