There are several types of damage that can be found in the male gamete. Genetic damage in spermatozoa can originate during spermatogenesis, or it can originate during transit in both male and female genital tracts. Damage can also be due to ageing, environmental or iatrogenic conditions, as well as to the protocols to cryopreserve and to select spermatozoa in assisted reproduction techniques. The purpose of this book is to provide a comprehensive resource for all possible DNA damages in sperm, the relation to fertility and infertility, and possible transgenerational heritable effects.

This volume seeks to understand how organisms and gene functions are influenced by environmental cues while accounting for variation that takes place within and among environmental populations and communities. Microbial Environmental Genomics (MEG) guides readers through methods to analyse the diversity of different organism types (archaea, bacteria, fungi, protists and microfauna), interactions between fungi and trees, and methods to identify and characterize functions and functional diversity of both pro- and eukaryotes. Written for the 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, Microbial Environmental Genomics (MEG) will serve as a primary research reference for researchers and research managers in environmental microbiology working in the expanding field of molecular ecology and environmental genomics.

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.

The ability of a single genome to give rise to hundreds of functionally distinct cell type programs is in itself remarkable. Pioneering studies over the past few decades have demonstrated that this plasticity is retained throughout development, a phenomenon of epigenetic programming and reprogramming that remains one of the most fascinating areas of modern biology, with major relevance to human health and disease. This book presents the basic biology involved, including key mechanistic insights into this rapidly growing field.

This second edition focuses on the study of human interphase chromosomes and its relation to health and disease. Orchestrated organization and behavior of the human genome in interphase nuclei at chromosomal level has been repeatedly shown to play a significant role in almost all basic biological processes involved in the processing and inheritance of genetic information within and between species. Accordingly, post-genomic bioscience appeals to basic and applied studies of interphase nuclei genetics and genomics with special attention to interphase chromosome behavior in health and disease. Additionally, elucidating the role of interphase chromosome behavior during development, chromosome/DNA replication, DNA reparation opens new horizons for basic and applied bioscience Studies of interphase nuclei have an appreciable impact on different areas of biomedical sciences such as cell biology, neurobiology, cancer research, developmental biology, epigenetics, cytogenetics, and medical genetics, as a whole. Moreover, development of innovative and emergent technologies to analyze interphase nuclei are closely associated with application of these techniques in diagnostic and research practices to solve reproductive problems (including infertility and spontaneous abortions), to investigate congenital malformations (including those produced by aneuploidy and other chromosome abnormalities); genetic diseases (including cardiac, immune, neurological and psychiatric diseases), and cancer. This second edition serves as a source of updated valuable information and promising ideas for a wide audience of professionals in biomedicine including researchers, scientists, and healthcare professionals in human genetics, cytogenetics, and developmental biology.

Written by leading researchers, this text explores the intersection of genetics and metabolomics, and points the way to more comprehensive studies of inborn variation of metabolism. All chapters refer to one or more published experimental datasets.

Today, individuals have greater access to information about their healththaneverbefore(Randeree,2009;Eysenbach,2008).Muchofthis changeisdue, inlargepart, toadvancesinbiotechnologyandtheseque- ing of the human genome (Manolio & Collins, 2009). It is now possible, forexample, forindividualstologontotheInternetand, forafeeofs- eral hundred dollars, order an at-home DNA collection kit and have the resultsofamyriadofgenetictestsdelivereddirectlytotheire-mailinbox (Gurwitz&Bregman-Eschet,2009).Insomecases, thesetestresultsmay indicatepersonalriskforcommonchronicdiseases, suchascertainforms ofcancer, diabetes, cardiovasculardisease, andseveralothers.Companies marketing these test kits often claim that promoting greater access to and awareness of the association between genes and health, and one's genetic susceptibilities to disease, leads to more proactive and insig- fulmethodsofindividualhealthmanagement(Hogarth, Javitt,&Melzer, 2008). Moreover, it is consistent with an emerging trend in medicine - that of consumer-oriented medicine - which places health information toolsdirectlyinthehandsofpatientsunderthepremiseoffosteringbetter patient-providercollaboration(Silvestre, Sue,&Allen,2009). Though the principles behind this direct-to-consumer approach to genetics seem laudable and perhaps even exciting, there is consid- ablecontroversyastowhat, ifany, utilitytheinformationactuallyholds (Geransar&Einsiedel,2008;Wasson, Cook,&Helzlsouer,2006).Unlike geneticteststhatarediagnostic(e.g., chromosomeanalysisforDowns- drome)orhighlypredictive(e.g., BRCA1andBRCA2testingforhereditary breast-ovarian cancer risk), this new wave of presymptomatic predictive genetictestsforcommondiseaseyieldsresultsthataremuchmoreunc- tainbecausethestatisticalmodelsonwhichtheyarepresentlybasedare imperfectandwithlimiteddata(Ng, Murray, Levy,&Venter,2009). Theabovescenarioraisesmanyquestionsfortoday'shealth-carec- sumers. For example, for whom is this information applicable, and for whatpopulationsorsubpopulationsisitnot?Underwhatcircumstances might this information be useful, and when should it be disregarded as irrelevant?Andperhapsmostimportantly, what, ifanything, canbedone inlightofinformationaboutpersonalgeneticrisktoeffectivelylowerthe oddsofbecomingsickandraisetheoddsofstayinghealthy? vii viii PREFACE Becausetheprevalenceofmostdiseasesvariesasafunctionofage, gender, race/ethnicity, and other personal characteristics, answers to these questions are complex and many are just beginning to be und- stood(Khouryetal.,2009).Someexpertshaveconcludedthattheanswers tosuchquestionsremainoutofreachatthepresenttimeandmayc- tinue to be elusive for another 5-10 years (Frazer, Murray, Schork, & Topol,2009).Yet, twenty-?rstcenturyhealth-careconsumers, providers, and policy makers face these choices now about incorporating personal genetic information into health management and often do so without a complete and accurate understanding of the potential impact of their decisionsonmultiplelevels(Carlson,2009).

The huge potential for gene therapy to cure a wide range of diseases has led to high expectations and a great increase in research efforts in this area, particularly in the study of delivery via viral vectors, widely considered to be more efficient than DNA transfection. In Viral Vectors for Gene Therapy: Methods and Protocols, experts in the field present a collection of their knowledge and experience featuring methodologies that involve virus production, transferring protocols, and evaluating the efficacy of gene products. While thoroughly covering the most popular viral vector systems of adenovirus, retrovirus, and adeno-associated virus, this detailed volume also explores less common viral vector systems such as baculovirus, herpes virus, and measles virus, the growing interest in which is creating a considerable demand for large scale manufacturing and purification procedures. Written in the highly successful Methods in Molecular Biology (TM) series format, many chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Viral Vectors for Gene Therapy: Methods and Protocols provides basic principles accessible to scientists from a wide variety of backgrounds for the development of gene therapy viral products that are safe and effective.

Medical research involving human subjects has contributed to considerable advancements in our knowledge, and to medical benefits. At the same time the development of new technologies as well as further globalisation of medical research raises questions that require the attention of researchers from a range of disciplines. This book gathers the contributions of researchers from nine different countries, who analyse recent developments in medical research from ethical, historical, legal and socio-cultural perspectives. In addition to reflections on innovations in science such as genetic databases and the concept of "targeted therapy" the book also includes analyses regarding the ethico-legal regulation of new technologies such as human tissue banking or the handling of genetic information potentially relevant for participants in medical research. Country and culture-specific aspects that are relevant to human medical research from a global perspective also play a part. The value of multi- and interdisciplinary analysis that includes the perspectives of scholars from normative and empirical disciplines is a shared premise of each contribution.

In this volume of Methods in Molecular Biology (TM), expert investigators offer comprehensive, complementary, and cutting-edge technologies for studies of gene regulation. The chapters of Gene Regulation: Methods and Protocols are organized to provide an integrated and a coherent view of control systems and their associated components. The protocols are broad in their scope. They include molecular, biochemical, spectroscopic techniques as well as high throughput strategies. 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. Comprehensive and broad in their scope, the protocols are useful to researchers in many disciplines including molecular biology, genomics, biochemistry, biomedicine, nutrition, and agricultural sciences.

This book examines in depth the evidence, clinical applications and potential cancer signatures in the circulation and discusses alterations in circulating cell-free nucleic acids, and circulating tumor DNA, as well as the epigenome, genome, transcriptome (coding and noncoding), proteome (both traditional serum proteins and proteomic profiles) and metabolome. Further, it highlights the clinical applications of circulating tumor cells for each cancer type and addresses the emerging importance of extracellular vesicular contents, including miRNA, oncogenes and drug resistant factors. As such, it offers a valuable reference guide for cancer researchers, oncologists, clinicians, surgeons, medical students, oncology nurses, diagnostic laboratories, and the pharmaceutical industry.

This volume provides a collection of methods and protocols detailing extracellular RNA and hopes to be a useful resource for those interested in this exciting and emerging field. Chapters are divided into four sections covering an overview of the field, approaches for the isolation of exRNA, protocols for detection and quantitation of exRNA, and approaches that can be useful for studies to evaluate potential therapeutic applications. 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, Extracellular RNA: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Signal transduction comprises the intracellular biochemical signals which induce the appropriate cell response to an external stimulus. The players in signal transduction are diverse, from small molecules as first messengers, to proteins, receptors, transcription factors, among many others. The different signaling pathways and the crosstalk between them originates the unique signaling profile of every cell type in the human body. The cell signaling specificity depends on several aspects including protein composition, subcellular localization and complexes and gene promoters. This textbook provides a comprehensive overview of the specific signaling pathways on a variety of human tissues. This information can be of great value for health science researchers, professionals and students to understand key pathways for tissue-specific functions in the plethora of signals, signals receptors, transducers and effectors. Chapter 3 and 15 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Primary immunodeficiency diseases, first recognized 60 years ago, are inherited disorders that affect human adaptive and innate immunity. In most cases, affected individuals experience recurrent infections, but they may also suffer from autoimmune diseases and malignancies. This third edition of Primary Immunodeficiency Diseases provides readers with the historic and scientific background, clinical presentations, immunologic characteristics, and the molecular/genetic underpinnings of this rapidly enlarging class of diseases. With up-to-date diagnostic tools and therapeutic options - from prophylactic anti-infective measures to hematopoietic stem cell transplantation and gene therapy - this volume will remain an authoritative resource on this increasingly important area.

Our understanding of the genetic and developmental mechanisms underlying scoliosis is rapidly evolving, this timely second edition of The Genetics and Development of Scoliosis is to provide researchers, clinicians, and students with the most current views in this field. This volume brings together leaders in understanding congenital and idiopathic scoliosis to present the current state of research, and to compare the genetic etiology of these conditions, in order to identify potential shared developmental mechanisms. This book will summarize the recent advances in studies of spinal development and how disruptions during embryogenesis in embryonic segmentation can lead to congenital vertebral defects. In addition, recent reports of genetic loci predisposing patients to develop juvenile and adolescent idiopathic scoliosis will be presented, and key clinical features are reviewed. Finally, there will be discussion of how genetic heterogeneity and gene-environment interactions may contribute to congenital scoliosis and isolated vertebral malformations.

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.

Angiogenesis is the growth of new blood vessels and is a key process which occurs during pathological disease progression. Excessive and damaging angiogenesis occurs in diseases such as cancer, diabetic retinopathies, age-related macular degeneration and atherosclerosis. In other diseases such as stroke and myocardial infarction, insufficient or improper angiogenesis results in tissue loss and ultimately higher morbidity and mortality. In this book we will begin by providing the reader with an overview of the process of angiogenesis including normal embryological development of blood vessels. The following chapters will each focus on a key angiogenic disease incorporating current scientific knowledge concerning the causes of activation of the "angiogenic switch," pathological consequences, current treatment options and future perspectives. Where appropriate, results from pre-clinical trials, novel imaging modalities and nanotechnological approaches will be incorporated into these sections. Finally, since it is now believed that the process of angiogenesis operated via different signalling mechanisms in different vascular beds, we will discuss our current understanding of this phenomenon. The target audience for this book would include researchers in all the basic sciences; post-graduate students at Universities and Institutes; pharmaceutical industries; clinicians working in vascular biology or tissue imaging; pathologists; neurologists; tumour biologists; ophthalmologists and cardiologists.

Androgens and androgen receptors (AR) play critical roles in the development and progression of prostate cancer, the most frequently diagnosed cancer and second leading cause of cancer death in US males. AR is an androgen-dependent DNA-binding transcription factor that regulates the expression of androgen-responsive genes. Identification and characterization of androgen-responsive genes provide insights into the cellular mechanisms of androgen action and may lead to new approaches in diagnosis, prognosis, prevention and/or treatment of prostate cancer. This volume provides critical information from well respected experts in the field. Some of the exciting topics include the new understanding of mechanisms underlining the regulation of androgen-responsive gene expression, and functions of various androgen-responsive genes in biological processes essential in carcinogenesis including cell growth, angiogenesis, and epithelial-to-mesenchyme transition (EMT). Other important aspects addressed are the current and potential clinic applications of knowledge on androgen-responsive gene regulation and function. This book is intended for researchers, scientists, faculty, and advanced graduate students with an interest in androgen action and prostate cancer.

There are now compelling human epidemiological and animal experimental data that indicate the risk of developing adult-onset complex diseases and neurological disorders are influenced by persistent epigenetic adaptations in response to prenatal and early postnatal exposures to environmental factors. Epigenetics refers to heritable changes in gene function that occur without a change in the sequence of the DNA. The main components of the epigenetic code are DNA methylation, histone modifications, and non-coding RNAs. The epigenetic programs are established as stem cell differentiate during embryogenesis, and they are normally faithfully reproduced during mitosis. Moreover, they can also be maintained during meiosis, resulting in epigenetic transgenerational disease inheritance, and also potentially introducing phenotypic variation that is selected for in the evolution of new species. The objective of this book is to provide evidence that environmental exposures during early development can alter the risk of developing medical conditions, such as asthma, autism, cancer, cardiovascular disease, diabetes, obesity, and schizophrenia later in life by modifying the epigenome.

Over the last two decades advances in genotyping technology, and the development of quantitative genetic analytical techniques have made it possible to dissect complex traits and link quantitative variation in traits to allelic variation on chromosomes or quantitative trait loci (QTLs). In Quantitative Trait Loci (QTLs):Methods and Protocols, expert researchers in the field detail methods and techniques that focus on specific components of the entire process of quantitative train loci experiments. These include methods and techniques for the mapping populations, identifying quantitative trait loci, extending the power of quantitative trait locus analysis, and case studies. Written in the highly successful Methods in Molecular Biology (TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Quantitative Trait Loci (QTLs):Methods and Protocols aids scientists in the further study of the links between phenotypic and genotypic variation in fields from medicine to agriculture, from molecular biology to evolution to ecology.

The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.

The earliest descriptions of human chromosomes initiated the genomics revolution that is now upon us. Array Comparative Genomic Hybridization: Protocols and Applications explores the scope of what is now possible as far as documenting abnormalities associated with several human cancers. While the technology for interrogating the human genome continues to evolve, refinement of comparative genomic hybridization (CGH) using array CGH and related technologies have provided enormous insight into human cancers at an affordable scale. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Array Comparative Genomic Hybridization: Protocols and Applications provides researchers with well-honed methodologies to learn these techniques for their own use in research or clinical diagnostic laboratories.

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.

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.

Recent developments in stem cell biology have opened new directions in cell therapy. This book provides the state-of-the-art developments in using biomaterials as artificial niches for engineering stem cells, both for the purpose of better understanding their biology under 3D biomimetic conditions as well as for developing new strategies for efficient long term maintenance and directed differentiation of stem cells into various therapeutic lineages. Animal and human stem cells of both embryonic and adult origin are discussed with applications ranging from nerve regeneration, orthopedics, cardiovascular therapy, blood cell generation and cancer therapy. Both synthetic and natural biomaterials are reviewed with emphasis on how material-stem cell interactions direct specific signaling pathways and ultimately modulate the cell fate. This book is valuable for biomaterial scientists, tissue engineers, clinicians as well as stem cell biologists involved in basic research and applications of adult and embryonic stem cells.