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Bart de Strooper: Macro Roles for MicroRNAs in the Life and Death of Neurons

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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.

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Dr Karen H Jobes,Mois Silva: Invitation to the Septuagint

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This comprehensive yet user-friendly primer to the Septuagint (LXX) acquaints readers with the Greek versions of the Old Testament. It is accessible to students, assuming no prior knowledge about the Septuagint, yet is also informative for seasoned scholars. The authors, both prominent Septuagint scholars, explore the history of the LXX, the various versions of it available, and its importance for biblical studies. This new edition has been substantially revised, expanded, and updated to reflect major advances in Septuagint studies. Appendixes offer helpful reference resources for further study.

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Craig Robson: Birds of South-East Asia

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The up-to-date text covers the identification, voice, habitat, behaviour and range of all the 1270 species and distinctive subspecies of this magnificent bird-rich region. The authoritative text is accompanied by over 140 full-colour plates painted by a range of expert artists and covering major plumage variations. Birds of South-East Asia is a complete field and reference guide to the birds of Thailand, Peninsular Malaysia, Singapore, Myanmar, Laos, Vietnam and Cambodia. It also covers a wide range of species found in the Indian subcontinent, China, Taiwan, Sumatra, Java, Bali, Borneo and the Philippines.

The Shack has touched millions of readers with its portrayal of a compassionate God in the face of great evil. Many have identified with the main character's Great Sadness, the terrible burden of grief that often accompanies and follows a deep loss, for the Great Sadness is part of the human condition. And it compels us to ask, Where is God? Who is God? Roger Olson, who has faced Birds of South-East Asia free epub his own Great Sadness, finds a good deal of comfort in this much beloved, story as have so many others. Some may ask, however, Is God really like that? Is that really how God responds to evil? Can God be trusted? Olson also viewsThe Shack with a theologian's eye and finds much sound truth. He delves into many of the significant issues raised by the book such as forgiving those who have done us great evil, how God acts in the world, how God is three persons in one and what difference this makes to us. While he offers his own criticisms of the book, he largely finds the truth about God in The Shack.

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Neal Shusterman,Brendan Shusterman: Challenger Deep

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National Book Award and Golden Kite Award Winner A captivating novel about mental illness that lingers long beyond the last page, Challenger Deep is a heartfelt tour de force by New York Times bestselling author Neal Shusterman. Caden Bosch is on a ship that's headed for the deepest point on Earth: Challenger Deep, the southern part of the Marianas Trench. Caden Bosch is a brilliant high school student whose friends are starting to notice his odd behavior. Caden Bosch is designated the ship's artist in residence to document the journey with images. Caden Bosch pretends to join the school track team but spends his days walking for miles, absorbed by the thoughts in his head. Caden Bosch is split between his allegiance to the captain and the allure of mutiny. Caden Bosch is torn. Challenger Deep is a deeply powerful and personal novel from one of today's most admired writers for teens. Laurie Halse Anderson, award-winning author of Speak, calls Challenger Deep "a brilliant journey across the dark sea of the mind; frightening, sensitive, and powerful. Simply extraordinary."

In World War One: A Short History, Norman Stone provides a terse, opinionated and wry short history of the First World War. In 1914 a new kind of war, and a new kind of world, came about. Fourteen million combatants died, a further twenty million were wounded, four empires were destroyed and even the victors' empires were fatally damaged. The First World War marked a revolution in the technology Challenger Deep download book of slaughter as trench warfare, artillery barrages, tanks and chemical warfare made their mark on the battlefield for the first time. The sheer complexity and scale of the war have encouraged historians to write books on a similar scale. But in only 140 pages, Norman Stone distils a lifetime of teaching, arguing and thinking to reframe the overwhelming disaster whose aftershocks shaped the rest of the twentieth century. 'Bold, provocative and witty ...one of the outstanding historians of our age' Spectator 'Do we need another history of the First World War? The answer in the case of Norman Stone's short book is, yes - because of its opinionated freshness and the unusual, sharp facts that fly about like shrapnel' Literary Review 'Exhilarating ...scintillating ...a heady cocktail' Observer 'Entertaining and insightful .

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David Evans: Art of Walking: A Field Guide

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"The Art of Walking: A Field Guide" is a unique look at walking as a mode of artistic practice and is the first book to explore this fascinating subject of how walking can be used as an artistic medium. An introductory essay identifies breaks and continuities between walking artists now and the pedestrian activities of the historic- and neo-avant-gardes of the early- and mid-20th Century, respectively. Subsequent visually-led sections deal with recent art engaging with different types of walkers including pilgrims, peripatetic writers and philosophers, dandies, drifters, marchers, stalkers, tour guides and dog walkers. Artists to be evaluated include Marina Abramovic and Ulay, Vito Acconci, Dennis Adams, Francis Alys, Keith Arnatt, Tim Brennan, Stanley Brouwn, Bruce Nauman, Sophie Calle, Janet Cardiff and George Bures Miller, Jeremy Deller, Simon Faithfull, Hamish Fulton, Regina Jose Galindo, Mona Hatoum, Akira Kanayama, Richard Long, The Long March Foundation, Melanie Manchot, Yoko Ono, Adrian Piper, Simon Pope and Kryzysztov Wodiczko.

Liza Campbell was the last child to be born at Cawdor Castle, as featured in "Macbeth". Her father Hugh, the 25th Thane of Cawdor, inherited good looks, wealth, an ancient title, three stately homes and 100,000 acres of land. But increasingly overwhelmed by his enormous responsibilities, Hugh turned to drink, drugs, and extramarital affairs. Until the castle was transformed into an arena of reckless profligacy, abuse and terrifying domestic violence, leading to the abrupt termination of a legacy that had been passed Death of a Hero download PDF down through the family for six hundred years. "Title Deeds" is a dark yet funny, contemporary fairy story about growing up in an old family where ancient curses and grisly past events are matched by the turmoil of a confusing and frightening present. Liza Campbell shows how even enormous wealth and privilege can hide unspoken abuse and misery: and what it is like to watch your father destroy himself and everything he holds dear.

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Harold Hall: Lathework: A Complete Course

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If fear of the unknown is all that is preventing you from embarking on the satisfying hobby of model engineering, then this is the book that will banish your concerns. Author Harold Hall has established his reputation as a mentor to tyro model engineers through the pages of Model Engineer magazine and Model Engineers' Workshop, of which he was the editor for a number of years. This book assumes no previous experience and using the medium of twelve lathe turning projects will lead prospective model engineers through all of the basic techniques needed to tackle ambitious projects. All of the projects are extensively illustrated and full working drawings accompany the text. Once followed through, the reader will have amassed a wealth of practical skills and a range of useful workshop tools and equipment.

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Mick Fleetwood,Anthony Bozza: Play on: Now, Then and Fleetwood Mac

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"After forty-six years of being on the road, now is the right time to look back in a way I've never done before: now and then. I'm looking forward to sharing it with you." Mick Fleetwood has been part of one of the world's most successful and adored bands for over four decades. Here he tells the full and candid story of that life, and what it is to be part of the ever evolving Fleetwood Mac. His all-access autobiography spans the career of one of classic rock's greatest drummers and band leaders, the co-founder of the deeply loved super group that bears his name. In this intimate portrait of a life lived in music, Fleetwood vividly recalls his upbringing in Cornwall, Egypt and Norway tapping along to whatever song was playing on the radio; his experiences as a musician in Sixties London; the early days of the band featuring Peter Green, and his close friendship with George Harrison and seemingly all of music royalty. Play On sheds new light on Fleetwood Mac's raucous history describing the highs and lows of being part of a band that he often single-handedly kept together. His love affair with Stevie Nicks, the creation of landmark albums like Rumours and Tusk, and the many incredible and outrageous moments of recording, touring, fighting, and loving with Fleetwood Mac: all are here. He describes his life's moments with the honesty and immediacy that his fans expect, taking us to the very heart of this multi layered life. It's been a tumultuous journey with the excesses of the band's huge success at times threatening to destroy what they strived so hard to create. But through it all it's been the drive to play on that has won out. Now, then, and always, it's Fleetwood Mac.

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Editors of Penthouse: Letters to Penthouse: Wives Gone Wild

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Donnel B. Stern: Partners in Thought: Working with Unformulated Experience, Dissociation, and Enactment

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Building on the innovative work of Unformulated Experience, Donnel B. Stern continues his exploration of the creation of meaning in clinical psychoanalysis with Partners in Thought. The chapters in this fascinating book are undergirded by the concept that the meanings which arise from unformulated experience are catalyzed by the states of relatedness in which the meanings emerge. In hermeneutic terms, what takes place in the consulting room is a particular kind of conversation, one in which patient and analyst serve as one another's partner in thought, an emotionally responsive witness to the other's experience. Enactment, which Stern theorizes as the interpersonalization of dissociation, interrupts this crucial kind of exchange, and the eventual breach of enactments frees analyst and patient to resume it. Later chapters compare his views to the ideas of others, considering mentalization theory and the work of the Boston Change Process Study Group. Approaching the link between dissociation and enactment via hermeneutics, metaphor, and narrative, among other perspectives, Stern weaves an experience-near theory of psychoanalytic relatedness that illuminates dilemmas clinicians find themselves in every day. Full of clinical illustrations showing how Stern works with dissociation and enactment, Partners in Thought is destined to take its place beside Unformulated Experience as a major contribution to the psychoanalytic literature.

This picture of the London of Queen Elizabeth (1558-1603) is the result of Liza Picard's curiosity about the practical details of daily life that almost every history book ignores. As seen in her two previous, highly acclaimed books-Restoration London and Dr. Johnson's London-she has immersed herself in contemporary sources of every kind. She begins with the River Thames, the lifeblood of Elizabethan London. The city, on the north bank of the river, was still largely confined within old Roman walls. Upriver at Westminster were the royal palaces, and between them and the crowded city the mansions of the great and the good commanded the river frontage. She shows us the interior decor of the rich and the not-so-rich, and what they were likely to be growing in their gardens. Then the Londoners of the time take the stage, in all their amazing finery. Plague, small-pox, and other diseases afflicted them. But food and drink, sex and marriage and family life provided comfort, a good education was always useful, and cares could be forgotten in a playhouse or the bear-baiting rings, or watching a good cockfight. Liza Picard's wonderfully skillful and vivid evocation of the London of four hundred years ago enables us Partners in Thought: Working with Unformulated Experience, Dissociation, and Enactment download ebook pdf to share the delights, as well as the horrors, of the everyday lives of sixteenth century Britain.

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Jonathan Herring: Criminal Law: Text, Cases, and Materials

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