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.

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.

According to the National Institute of Health, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of basic biological processes affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine. In addition, rapid advances in understanding the patterns of human genetic variation and maturing high-throughput, cost-effective methods for genotyping are providing powerful research tools for identifying genetic variants that contribute to health and disease. (good paragraph)
This burgeoning science merges the principles of statistics and genetics studies to make sense of the vast amounts of information available with the mapping of genomes. In order to make the most of the information available, statistical tools must be tailored and translated for the analytical issues which are original to large-scale association studies. This book will provide researchers with advanced biological knowledge who are entering the field of genome-wide association studies with the groundwork to apply statistical analysis tools appropriately and effectively. With the use of consistent examples throughout the work, chapters will provide readers with best practice for getting started (design), analyzing, and interpreting data according to their research interests. Frequently used tests will be highlighted and a critical analysis of the advantages and disadvantage complimented by case studies for each will provide readers with the information they need to make the right choice for their research. Additional tools including links to analysis tools, tutorials, and references will be available electronically to ensure the latest information is available.
* Easy access to key information including advantages and disadvantage of tests for particular applications, identification of databases, languages and their capabilities, data management risks, frequently used tests
* Extensive list of references including links to tutorial websites
* Case studies and Tips and Tricks

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 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.

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.

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.

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.

Circadian rhythms are such an innate part of our lives that we rarely pause to speculate why they even exist. Some studies have suggested that the disruption of the circadian system may be causal for obesity and manifestations of Metabolic Syndrome (MetS). Shift-work, sleep-deprivation and bright-light-exposure at night are related to increased adiposity (obesity) and prevalence of MetS. It has been provided evidence of clock genes expression in human adipose tissue and demonstrated its association with different components of the MetS. Moreover, current studies are illustrating the particular role of different clock genes variants and their predicted haplotypes in MetS.

The purpose of Chronobiology and Obesity is to describe the mechanisms implicated in the interaction between chonodisruption and metabolic-related illnesses, such as obesity and MetS, with different approaches."

Together with early theoretical work in population genetics, the debate on sources of genetic makeup initiated by proponents of the neutral theory made a solid contribution to the spectacular growth in statistical methodologies for molecular evolution. Evolutionary Genomics: Statistical and Computational Methods is intended to bring together the more recent developments in the statistical methodology and the challenges that followed as a result of rapidly improving sequencing technologies. Presented by top scientists from a variety of disciplines, the collection includes a wide spectrum of articles encompassing theoretical works and hands-on tutorials, as well as many reviews with key biological insight. Volume 2 begins with phylogenomics and continues with in-depth coverage of natural selection, recombination, and genomic innovation. The remaining chapters treat topics of more recent interest, including population genomics, -omics studies, and computational issues related to the handling of large-scale genomic data. Written in the highly successful Methods in Molecular Biology (TM) series format, this work provides the kind of advice on methodology and implementation that is crucial for getting ahead in genomic data analyses. Comprehensive and cutting-edge, Evolutionary Genomics: Statistical and Computational Methods is a treasure chest of state-of the-art methods to study genomic and omics data, certain to inspire both young and experienced readers to join the interdisciplinary field of evolutionary genomics.

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

Due to their novel concepts and extraordinary high-throughput sequencing capacity, the "next generation sequencing" methods allow scientists to grasp system-wide landscapes of the complex molecular events taking place in various biological systems, including microorganisms and microbial communities. These methods are now being recognized as essential tools for a more comprehensive and deeper understanding of the mechanisms underlying many biological processes. In High-Throughput Next Generation Sequencing: Methods and Applications, experts in the field explore the most recent advances in the applications of next generation sequencing technologies with an emphasis on microorganisms and their communities; however, the methods described in this book will also offer general applications relevant to the study of any living organisms. 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 cutting-edge, High-Throughput Next Generation Sequencing: Methods and Applications is an excellent collection of chapters to aid all scientists who wish to apply these innovative research tools to enhance their own pursuits in microbiology and also biology in general.

This manual offers detailed protocols for fluorescence in situ hybridization (FISH) and comparative genomic hybridization approaches, which have been successfully used to study various aspects of genomic behavior and alterations. Methods using different probe and cell types, tissues and organisms, such as mammalians, fish, amphibians (including lampbrush-chromosomes), insects, plants and microorganisms are described in 57 chapters. In addition to multicolor FISH procedures and special applications such as the characterization of marker chromosomes, breakpoints, cryptic aberrations, nuclear architectures and epigenetic changes, as well as comparative genomic hybridization studies, this 2nd edition describes how FISH can be combined with other techniques. The latter include immunostaining, electron microscopy, single cell electrophoresis and microdissection. This well-received application guide provides essential protocols for beginning FISHers and FISH experts alike working in the fields of human genetics, microbiology, animal and plant sciences.

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

Neuropsychiatric disorders such as schizophrenia, mood disorders, Alzheimer s disease, epilepsy, alcoholism, substance abuse and others are one of the most debilitating illnesses worldwide characterizing by the complexity of the causes, and lacking the laboratory tests that may promote diagnostic and prognostic procedures. Recent advances in neuroscience, genomic, genetic, proteomic and metabolomic knowledge and technologies have opened the way to searching biomarkers and endophenotypes, which may offer powerful and exciting opportunity to understand the etiology and the underlying pathophysiological mechanisms of neuropsychiatric disorders. The challenge now is to translate these advances into meaningful diagnostic and therapeutic advances. This book offers a broad synthesis of the current knowledge about diverse topics of the biomarker and endophenotype strategies in neuropsychiatry.

The book is organized into four interconnected volumes: Neuropsychological Endophenotypes and Biomarkers (with overview of methodological issues of the biomarker and endophenotype approaches in neuropsychiatry and some technological advances), Neuroanatomical and Neuroimaging Endophenotypes and Biomarkers, Metabolic and Peripheral Biomarkers and Molecular Genetic and Genomic Markers . The contributors are internationally and nationally recognized researchers and experts from 16 countries. This four-volume handbook is intended for a broad spectrum of readers including neuroscientists, psychiatrists, neurologists, endocrinologists, pharmacologists, clinical psychologists, general practitioners, geriatricians, health care providers in the field of neurology and mental health interested in trends that have crystallized in the last decade, and trends that can be expected to further evolve in the coming years. It is hoped that this book will also be a useful resource for the teaching of psychiatry, neurology, psychology and mental health. "

Despite the best efforts of many and despite landmark discoveries and experimental ingenuity, challenges in the pursuit of research related to olfactory receptors (ORs) continue to exist. In Olfactory Receptors: Methods and Protocols, experts in the field contribute chapters that serve to address these challenges. The volume consists of several sections: knowledge dissemination of ORs, theoretical assessments of OR structure and function, as well as development and use of expression systems and experimental functional analysis. 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 tips on troubleshooting and avoiding known pitfalls. Concise and practical, Olfactory Receptors: Methods and Protocols seeks to aid researchers in furthering the knowledge of olfaction and moving us ever closer to the thrilling discoveries that will follow.

"Regulatory Non-Coding RNAs: Methods and Protocols" offers a collection of methods for those interested in the discovery, localization, and functional analysis of these non-coding transcripts that have the potential and ability to orchestrate and control gene expression. After a review of the field, this detailed volume continues with methods useful for the study of siRNAs, microRNAs and their targets, techniques concerned with long non-coding RNAs, as well as studies of the critical parameters of functional non-coding RNA protein-RNA interactions and the environment in which they act. Written for the highly successful "Methods in Molecular Biology" series, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and tips for troubleshooting and avoiding known pitfalls.

Dependable and easy to use, "Regulatory Non-Coding RNAs: Methods and Protocols" provides a current, state-of-the-art collection of methods and approaches that will be of value to researchers in this expanding and fascinating field.

Progress in functional proteomics has been limited for a long time, partially caused by limitations in assay sensitivity and sample capacity; however, protein microarrays have the ability to overcome these limitations so that a highly parallel analysis of hundreds of proteins in thousands of samples is attainable. In Protein Microarrays: Methods and Protocols, expert researchers in the field present an up-to-date collection of robust strategies in the field of protein microarrays and summarize recent advantages in the field of printing technologies, the development of suitable surface materials, as well as detection and quantification technologies. 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 notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Protein Microarrays: Methods and Protocols aims to stimulate the application and further advancement of this powerful technology in labs worldwide.

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

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

Many fundamental discoveries concerning epigenetics and the elucidation of mechanisms of epigenetic regulation have developed from studies performed in plants. In Plant Epigenetics and Epigenomics: Methods and Protocols, leading scientists in the epigenetics field describe comprehensive techniques that have been developed to understand the plant epigenetic landscape. These include recently developed methods and techniques for analysis of epigenetically regulated traits, such as flowering time, transposon activation, genomic imprinting and genome dosage effects. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoidance of known pitfalls. Authoritative and practical, Plant Epigenetics and Epigenomics: Methods and Protocols seek to aid scientists in the further study of plant epigenetic phenomena using advanced contemporary methods.

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

Plants are amazing organisms to study, some are important sources for pharmaceuticals, and others can help to elucidate molecular mechanisms required for a plant's development and its interactions with the biotic or abiotic environment. Functional genomics is vastly lagging behind the speed of genome sequencing as high-throughput gene function assays are difficult to design, specifically for non-model plants. Bioinformatics tools are useful for gene identification and annotation but are of limited value for predictions concerning gene functions as gene functions are uncovered best by experimental approaches. Virus-Induced-Gene-Silencing (VIGS) is an easy to use, fast, and reliable method to achieve down regulation of target gene expression. Virus-Induced Gene Silencing: Methods and Protocols provides detailed protocols for VIGS experiments in several plant species including model and non-model plants. Also included in this book are recently developed protocols for VIGS-derived microRNA production in the plant or protein over expression, as well as chapters devoted to summarizing the molecular mechanisms of VIGS action and the vector systems developed so far. 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, Virus-Induced Gene Silencing: Methods and Protocols serves as a valuable resource for researchers from diverse fields of plant biology interested in experimental approaches to analyzing gene functions.