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簡(jiǎn)介：TIBIALCOMPONENTFIXATIONWITHAPERIAPATITECOATINGEVALUATIONBYRADIOSTEREOMETRICANALYSISINACANINETOTALKNEEARTHROPLASTYMODELMATTHEWJALLEN,VETMB,PHD,YKENDALLALEONE,BS,YMICHAELJDUNBAR,MD,PHD,ZAMOSRACE,PHD,YPAULAFROSENBAUM,PHD,§ANDJONATHANMSACKS,MS,MBA∥ABSTRACTCEMENTLESSFIXATIONFORTHETIBIALCOMPONENTINTOTALKNEEARTHROPLASTYTKAREMAINSPROBLEMATICPERIAPATITEPA,ASOLUTIONDEPOSITEDHYDROXYAPATITE,ISUNDERINVESTIGATIONASANOPTIONFORIMPROVINGTHEFIXATIONOFCEMENTLESSTIBIALCOMPONENTSINTHISSTUDY,RADIOSTEREOMETRICANALYSISWASUSEDTODOCUMENTIMPLANTMIGRATIONIN48DOGSTHATUNDERWENTTKAWITHCEMENTLESS,PACOATED,ORCEMENTEDTIBIALCOMPONENTSMIGRATIONAT12WEEKSWASSIMILARINTHE2GROUPSAT12MONTHS,THEREWASGREATERMIGRATIONINTHEPACOATEDGROUP,BUTTHEDIFFERENCEBETWEENTHE2GROUPSWASBELOWTHETHRESHOLDCONSIDEREDCLINICALLYSIGNIFICANTINTHISCANINETKAMODEL,CEMENTLESSFIXATIONWITHPAPERFORMEDLESSWELLTHANDIDCEMENTEDFIXATION,BUTNOTTOADEGREETHATWOULDMAKEACLINICALDIFFERENCEINTHESHORTTERMKEYWORDSIMPLANTMIGRATION,DOG,ARTHROPLASTY,BONECEMENT,HYDROXYAPATITE?2012ELSEVIERINCALLRIGHTSRESERVEDCEMENTLESSFIXATIONOFFERSSIGNIFICANTPOTENTIALADVANTAGESOVERCEMENTEDFIXATIONFORTOTALJOINTARTHROPLASTYINADDITIONTOTHEELIMINATIONOFBONECEMENTASASOURCEOFPARTICULATEDEBRIS13,CEMENTLESSFIXATIONISMOREAMENABLETOMINIMALLYINVASIVESURGICALAPPROACHESANDBETTERPRESERVESPERIPROSTHETICBONESTOCKATTHETIMEOFSURGERY4,5WITHTHECURRENTTRENDTOWARDPERFORMINGTOTALJOINTARTHROPLASTYINYOUNGERPATIENTS6ANDPATIENTSWITHHIGHERBODYMASSINDICES7,PRESERVATIONOFBONEMASSMAYBECRITICALLYIMPORTANTINOPTIMIZINGTHEMECHANICALINTEGRITYOFTHEBONEIMPLANTINTERFACEANDENSURINGIMPLANTLONGEVITYALTHOUGHCEMENTLESSIMPLANTSHAVEASUCCESSFULTRACKRECORDINTOTALHIPARTHROPLASTY810,EXPERIENCETODATEWITHTRADITIONALBONEINGROWTHSURFACESBEADS,FIBERMESH,ETCHAVEPRODUCEDMIXEDRESULTSWITHTOTALKNEEARTHROPLASTYTKAIMPLANTS1113DATAFROMTHESWEDISHKNEEARTHROPLASTYREGISTRYINDICATETHATTHERISKOFASEPTICLOOSENINGISSIGNIFICANTLYHIGHERWITHCEMENTLESSTKAIMPLANTSTHANWITHCEMENTEDIMPLANTS14THEUSEOFABIOACTIVECOATINGSUCHASHYDROXYAPATITEHAHASBEENSHOWNTOENHANCEBONEAPPOSITIONANDIMPROVEIMPLANTFIXATIONINANIMALMODELS1517,ANDTHEREISWIDESPREADINTERESTINDEVELOPINGTHESECOATINGSFORTKAIMPLANTSHOWEVER,CONCERNSREMAINTHATVARIATIONSINCOATINGCOMPOSITIONANDDEPOSITIONMETHODSMAKEITVERYHARDTOOBTAINPREDICTABLEOSSEOINTEGRATIONINTKAASNEWCOATINGMETHODOLOGIESANDINGROWTHSURFACESAREDEVELOPED,THEREISAPRESSINGNEEDFORPRECLINICALDATATOSUPPORTTHESAFETYANDEFFICACYOFTHESECANDIDATECOATINGSANDFIXATIONSURFACESINANIMALMODELSTHATFAITHFULLYRECAPITULATETHECLINICALFEATURESOFTKAINHUMANSTHESPECIFICAIMOFTHISSTUDYWASTODETERMINEWHETHERANEW,SOLUTIONDEPOSITEDFORMOFHAPERIAPATITE,ORPASTRYKERORTHOPAEDICS,MAHWAH,NJ18PROVIDESEFFECTIVEFIXATIONOFTHETIBIALCOMPONENTINCEMENTLESSTKABECAUSEMOSTPRECLINICALRESEARCHONFROMTHEDEPARTMENTOFVETERINARYCLINICALSCIENCES,THEOHIOSTATEUNIVERSITY,COLUMBUS,OHIOYDEPARTMENTOFORTHOPEDICSURGERY,SUNYUPSTATEMEDICALUNIVERSITY,SYRACUSE,NEWYORKZDEPARTMENTOFORTHOPEDICSURGERY,DALHOUSIEUNIVERSITY,NOVASCOTIA,CANADA§DEPARTMENTOFPUBLICHEALTHANDPREVENTIVEMEDICINE,SUNYUPSTATEMEDICALUNIVERSITY,SYRACUSE,NEWYORKAND∥STRYKERORTHOPAEDICS,MAHWAH,NEWJERSEYSUBMITTEDAPRIL26,2011ACCEPTEDDECEMBER24,2011THECONFLICTOFINTERESTSTATEMENTASSOCIATEDWITHTHISARTICLECANBEFOUNDATDOI101016/JARTH201112029REPRINTREQUESTSMATTHEWJALLEN,VETMB,PHD,DEPARTMENTOFVETERINARYCLINICALSCIENCES,THEOHIOSTATEUNIVERSITY,601VERNONLTHARPST,COLUMBUS,OH43210?2012ELSEVIERINCALLRIGHTSRESERVED08835403/270600523600/0DOI101016/JARTH2011120291138THEJOURNALOFARTHROPLASTYVOL27NO62012RADIOGRAPHSWEREOBTAINEDTODOCUMENTACCURATEPOSITIONINGOFTHEIMPLANT,ASECONDDOSEOFANTIBIOTICSWASADMINISTERED,ANDAROBERTJONESBANDAGEWASAPPLIEDTHEDOGWASTHENTRANSFERREDTOASTAINLESSSTEELRECOVERYCAGESHORLINE,KANSASCITY,KANFOROVERNIGHTHOUSINGPOSTOPERATIVEPAINMANAGEMENTINCLUDEDOPIATEANALGESICSMORPHINE10MGIMEVERY6TO12HOURSFOR2DAYSPOSTOPERATIVELYNONSTEROIDALANTIINFLAMMATORYAGENTSCARPROFEN100MGORALLY,ONCEDAILYANDANTIBIOTICSCEPHALEXIN500MGORALLY,TWICEDAILYWEREGIVENONTHEFIRSTPOSTOPERATIVEMORNINGANDCONTINUEDFOR7TO10DAYSPOSTSURGERYTHEBANDAGEWASTYPICALLYREMOVED3TO4DAYSPOSTSURGERYSKINSTAPLESWEREREMOVED8TO10DAYSPOSTSURGERYTHEANIMALCARESTAFFCHECKEDTHEANIMALSATLEASTTWICEDAILY,ANDANYANIMALSHOWINGSIGNSOFPAINORDISTRESSWASREFERREDTOTHEATTENDINGVETERINARIANANIMALSWEREALSOEXAMINED5DAYS/WKBYONEOFTHETECHNICIANSONTHESTUDYBODYTEMPERATUREWASRECORDED,ANDTHESKININCISIONWASCHECKEDFORSIGNSOFINFLAMMATIONAND/ORINFECTIONONCETHESKINSTAPLESHADBEENREMOVED,THEFOCUSCHANGEDTOEVALUATINGKNEEFUNCTIONANDLIMBUSEDOGSWEREALLOWEDOUTOFTHEIRKENNELSFORPERIODSOFUPTO15MINUTESFROMWEEKS2THROUGH6,WITHTHEEXPECTATIONBEINGTHATLIMBUSEWOULDGRADUALLYINCREASEOVERTHISPERIODFROMWEEK6ONWARD,DOGSWEREALLOWED30MINUTESOFUNRESTRICTEDACTIVITYPERDAYPASSIVEJOINTRANGEOFMOTIONWASMEASUREDWITHAGONIOMETER,ANDLAMENESSWASEVALUATEDUSINGANESTABLISHEDSCORINGSCHEME27AT6,12,26,AND52WEEKSAFTERSURGERYBIPLANARORTHOGONALVIEWRADIOGRAPHSFORRSAWEREOBTAINEDWITHTHEANIMALUNDERHEAVYSEDATIONWITHMEDETOMIDINEHYDROCHLORIDE750ΜG/M2IVTHEOPERATEDSTIFLEJOINTWASPOSITIONEDINTHEKNEECAGECAGE10RSABIOMEDICALWITHTHELONGAXISOFTHEHINDLIMBPARALLELTOTHEAXESOFTHELABORATORYCOORDINATESYSTEMTHEINITIALBASELINEEXAMINATIONWASTYPICALLYPERFORMED1WEEKAFTERSURGERY,ANDFOLLOWUPEXAMINATIONSWEREPERFORMEDAT6,12,26,AND52WEEKSPOSTSURGERYMIGRATIONOFTHETIBIALTRAYWASDETERMINEDBYMEASURINGRELATIVEMOTIONBETWEENTHEIMPLANTANDTHEPROXIMALTIBIATHEREFERENCESEGMENTTHEMEANERROROFRIGIDBODYFITTINGWASUSEDASANESTIMATEOFTHESTABILITYOFTHEMARKERSWITHINTHEREFERENCEANDMOVINGSEGMENTSINTHISSTUDY,AMEANERROROFLESSTHAN02MMWASCONSIDEREDACCEPTABLE28THEDISTRIBUTIONOFTHEMARKERSWITHINTHE2SEGMENTSWASQUANTIFIEDASTHECONDITIONNUMBER,WITHACONDITIONNUMBEROFLESSTHAN150BEINGCONSIDEREDACCEPTABLEFORTHISSTUDY,ASISCURRENTPRACTICEWITHCLINICALRSAINHUMANS29MIGRATIONOFTHETIBIALTRAYINRELATIONTOTHEPROXIMALTIBIAWASDESCRIBEDASROTATIONAROUNDORTRANSLATIONALONGTHE3CARDINALAXES,X,Y,ANDZGLOBALANALYSISOFMAXIMALIMPLANTMIGRATIONWASPERFORMEDUSINGTHEFIG1ACEMENTEDLEFTANDCEMENTLESSRIGHTTIBIALCOMPONENTSUSEDINTHISSTUDYCLOSEUPIMAGESOFTHEMORPHOLOGYOFTHECEMENTEDBANDCEMENTLESSCFIXATIONSURFACES1140THEJOURNALOFARTHROPLASTYVOL27NO6JUNE2012

簡(jiǎn)介：中文中文7200字出處出處ALLENMJ,LEONEKA,DUNBARMJ,ETALTIBIALCOMPONENTFIXATIONWITHAPERIAPATITECOATINGEVALUATIONBYRADIOSTEREOMETRICANALYSISINACANINETOTALKNEEARTHROPLASTYMODELJJOURNALOFARTHROPLASTY,2012,27611381348犬全膝關(guān)節(jié)置換模型使用犬全膝關(guān)節(jié)置換模型使用PAPA涂層脛骨假體的影像學(xué)評(píng)估涂層脛骨假體的影像學(xué)評(píng)估ALLENMJ,LEONEKA,DUNBARMJ,ETAL摘要摘要全膝關(guān)節(jié)置換脛骨假體的非骨水泥固定仍存在問(wèn)題。PERIAPATITE（PA）是一種溶液沉積羥基磷灰石，可作為一種改善脛骨假體非骨水泥固定的解決方案，相關(guān)研究正在進(jìn)行中。本研究將PA涂層脛骨假體和骨水泥脛骨假體植入48只犬體內(nèi)，使用放射體積測(cè)定法（RADIOSTEREOMETRICANALYSIS，RAS）分析假體移位情況。術(shù)后12周兩組沒(méi)有差異。術(shù)后12個(gè)月PA涂層組位移較大，但兩組間的差異均低于閾值，不存在臨床意義。本次犬模型實(shí)驗(yàn)中PA涂層遜于骨水泥組，但這種差異尚未產(chǎn)生短期臨床差異。相比骨水泥固定而言，全膝關(guān)節(jié)置換非骨水泥固定有著明顯的潛在優(yōu)勢(shì)。除了可以消除骨水泥顆粒碎屑來(lái)源13，因非骨水泥固定符合微創(chuàng)手術(shù)入路，術(shù)中還可更好地保留假體周圍骨量4,5。在當(dāng)前全膝關(guān)節(jié)置換患者更年輕化6、體重指數(shù)更高7的趨勢(shì)背景下，保留骨量在最優(yōu)化骨假體界面的力學(xué)性能完整性以及假體壽命更長(zhǎng)方面有重要意義。盡管在全髖關(guān)節(jié)置換中非骨水泥假體已經(jīng)取得了成功810，然而到目前為止，就常用的全膝關(guān)節(jié)置換骨長(zhǎng)入表面假體（珍珠面假體、纖維網(wǎng)孔假體等）所取得的經(jīng)驗(yàn)很不一致1113。瑞典膝關(guān)節(jié)置換注冊(cè)登記機(jī)構(gòu)的數(shù)據(jù)顯示，非骨水泥假體無(wú)菌性松動(dòng)的風(fēng)險(xiǎn)顯著高于骨水泥型假體14。動(dòng)物模型實(shí)驗(yàn)證實(shí)，生物活性涂層假體如羥基磷灰石（HYDROXYAPATITE，HA）可以促進(jìn)骨沉積，增加假體的穩(wěn)定性1517，由此引起學(xué)術(shù)界研究全髖關(guān)節(jié)置換假體涂層的廣泛興趣。然而，涂層成分和沉積方法的的不同使得預(yù)測(cè)TKA術(shù)后骨形成情況很困難。隨著對(duì)新涂層方法和骨長(zhǎng)入界面的研究開(kāi)發(fā)，目前迫切需要這些候選涂層和固定界面在動(dòng)物模型中安全性和有效性的臨床前數(shù)據(jù)，以便判斷在人TKA中的使用。本研究旨在評(píng)估一種新型溶液沉積形式的羥基磷灰石（PERIAPATITE，PA；STRYKERORTHOPAEDICS，MAHWAH，NJ）18能否在非骨水泥TKA中提供有效脛骨假體固定。由于大多數(shù)脛骨假體固定的臨床前實(shí)驗(yàn)研究均用犬作為實(shí)驗(yàn)對(duì)象1922，本研究同樣也使用犬類模型。由于放射體積測(cè)定分析（RADIOSTEREOMETRICANALYSIS，RSA）是測(cè)量人TKA假體移動(dòng)的標(biāo)準(zhǔn)2326，本次臨床前動(dòng)物實(shí)驗(yàn)也采用此項(xiàng)技術(shù)。本研究假設(shè)PA涂層非骨水泥假體會(huì)比骨水泥假體產(chǎn)生更大的移動(dòng)，但這種差距尚無(wú)臨床意義。材料與方法材料與方法本研究從MARSHALLBIORESOURCES（NORTHBLUFF，NY）采購(gòu)48只骨骼成熟的雄性獵犬（12月齡，體重為25～30千克），在標(biāo)準(zhǔn)實(shí)驗(yàn)室環(huán)境下（12/12小時(shí)晝夜交替；室溫68～72°F；濕度30～70）飼養(yǎng)。使用標(biāo)準(zhǔn)干犬糧喂養(yǎng)（“實(shí)驗(yàn)用5006犬糧”；OLDMOTHERHUBBARD，LOWELL，MASS），術(shù)后第一周加用桶裝犬糧（“NEUTRAMEAT”；OLDMOTHERHUBBARD）。動(dòng)物被隨機(jī)分入兩組（骨水泥組與非骨水泥組），每組又分為4小組，分別于術(shù)后6周、12周、26周或52周（表1）處死實(shí)驗(yàn)動(dòng)物。所有涉及動(dòng)物的操作均接受動(dòng)物飼養(yǎng)使用委員會(huì)全程檢查并獲得批準(zhǔn)。鈷鉻合金（COCR）鑄造（美國(guó)材料實(shí)驗(yàn)協(xié)會(huì)F75）股骨部分與脛骨組件。假體僅有一個(gè)型號(hào)（圖1A）。水泥型脛骨組件固定表面經(jīng)標(biāo)準(zhǔn)噴砂磨光處理（圖1B）。非骨水泥型的人類全膝置換相對(duì)應(yīng)，本研究還分析了某點(diǎn)受到的合力（MAXIMUMTOTALPOINTMOTION，MTPM），測(cè)量串珠受力后的最大點(diǎn)運(yùn)動(dòng)，因?yàn)樵摍z查常用于測(cè)量假體的固定情況25。最后通過(guò)測(cè)量Y軸上下的平移分別評(píng)估脛骨托的上抬和下沉情況29。由于文獻(xiàn)中尚無(wú)RSA在犬類TKA中的數(shù)據(jù)，本研究在46條犬身上進(jìn)行了171次重復(fù)RSA檢查，了解該方法在犬類中應(yīng)用的精確性（可重復(fù)性）。所有實(shí)驗(yàn)動(dòng)物均接受兩次影像學(xué)檢查，希望減少兩次檢查中的水平和旋轉(zhuǎn)誤差至0。計(jì)算零運(yùn)動(dòng)對(duì)比中誤差的標(biāo)準(zhǔn)差，評(píng)價(jià)其精確度30，根據(jù)ALTMAN等31的方法測(cè)量三軸位移的95可信區(qū)間31。研究結(jié)束時(shí)靜脈注射過(guò)量戊巴比妥（FATALPLUS；VORTECHPHARMACEUTICALS，DEARBORN，MICH）處死實(shí)驗(yàn)動(dòng)物。髖部離斷右后肢，清理軟組織，拍攝其正側(cè)位片。切斷脛骨近端，將其包裹在濕紗布中，準(zhǔn)備進(jìn)行機(jī)械力學(xué)測(cè)試。取出超高分子聚乙烯脛骨內(nèi)襯，用牙科水泥將脛骨遠(yuǎn)端固定在方形鋁框中。根據(jù)脛骨托內(nèi)部形狀定做夾具，確保假體與固定框之間對(duì)線恒定。為提供測(cè)量脛骨假體微動(dòng)時(shí)的骨性參考，在脛骨上打入一根不銹鋼釘。鉆頭導(dǎo)引器指向脛骨托，確保鋼釘位置恒定。將測(cè)試標(biāo)本固定于材料測(cè)試系統(tǒng)（MATERIALSTESTINGSYSTEM，MTS）的框架上，配以軸向和旋轉(zhuǎn)調(diào)節(jié)器和444N的元件，此時(shí)脛骨托與調(diào)節(jié)器平行。使用一個(gè)指向脛骨托的鋼制托盤，支撐一個(gè)鋁臂和一對(duì)鋼球（圖2）。將內(nèi)外側(cè)夾具標(biāo)尺安裝于鋁臂和脛骨上的參照鋼針之間。這些標(biāo)尺記錄脛骨托相對(duì)于脛骨的內(nèi)外側(cè)傾角和上下位移。將平行的線狀推桿插入脛骨平臺(tái)上的鋼球中。鋼球同心于脛骨內(nèi)襯的球形表面。通過(guò)一個(gè)離軸的樞轉(zhuǎn)板將載荷從MTS十字頭轉(zhuǎn)移至推桿，此時(shí)可以通過(guò)旋轉(zhuǎn)調(diào)節(jié)器調(diào)整內(nèi)外側(cè)載荷。向假體承重板施加100N的軸向載荷并維持。隨后在±14°之間旋轉(zhuǎn)調(diào)節(jié)器，頻率為025赫茲，使假體內(nèi)外側(cè)載荷在100N的10～90之間周期性變化。記錄夾具標(biāo)尺在調(diào)節(jié)器旋轉(zhuǎn)極端的數(shù)值，共58個(gè)循環(huán)。由于參考釘?shù)拈L(zhǎng)度已知，可以使用夾具標(biāo)尺的位移計(jì)算內(nèi)外側(cè)的傾斜度。使用SPSS170（SPSSINC，CHICAGOILL）軟件統(tǒng)計(jì)分析描述性和分析性RSA數(shù)據(jù)。根據(jù)最近的RSA臨床指南29，本研究在比較兩組間位移時(shí)采用絕對(duì)值。在描述階段匯總因變量（X、Y、Z軸上的旋轉(zhuǎn)和平移；MTPM；RV；最大下沉和抬高）的頻率，并計(jì)算各個(gè)時(shí)間點(diǎn)（術(shù)后6周、12周、26周和52周）的均值和標(biāo)準(zhǔn)差、最小值、最大值和四分位數(shù)。大多數(shù)變量為非正態(tài)分布，因此使用MANNWHITNEYU檢驗(yàn)比較兩組在各個(gè)時(shí)間點(diǎn)的差異，P005）。術(shù)后X片確認(rèn)所有實(shí)驗(yàn)動(dòng)物的假體均準(zhǔn)確植入。盡管本研究?jī)H使用同一尺寸的脛骨假

簡(jiǎn)介：中文中文1萬(wàn)字萬(wàn)字出處出處MEDAF,FOLCIM,BACCARELLIA,ETALTHEEPIGENETICSOFAUTOIMMUNITYJCELLULARMOLECULARIMMUNOLOGY,2011,83226236自身免疫表觀遺傳學(xué)自身免疫表觀遺傳學(xué)摘要摘要自身免疫性疾病的病因始終不為人們所知。同卵雙生子的疾病共顯率低于50，然而全基因組關(guān)聯(lián)研究只在一小部分病人發(fā)現(xiàn)了顯著關(guān)聯(lián)性。這個(gè)證據(jù)強(qiáng)烈支持了還有其他的補(bǔ)充機(jī)制涉及到了基因表達(dá)的調(diào)節(jié)過(guò)程最終導(dǎo)致了顯著的自身免疫病。組蛋白翻譯后修飾以及DNA甲基化是兩個(gè)主要的表觀遺傳學(xué)機(jī)制可能導(dǎo)致免疫耐受的下降以及自身免疫疾病的持續(xù)。在最近幾年對(duì)臨床以及實(shí)驗(yàn)的研究中提出了表觀遺傳學(xué)可能使我們更容易理解自身免疫病的起病和疾病的持續(xù)。更特殊的是，數(shù)據(jù)顯示表觀遺傳學(xué)的改變?cè)谙到y(tǒng)性紅斑狼瘡，風(fēng)濕性關(guān)節(jié)炎，多發(fā)性硬化以及其他自身免疫病的影響，在某些病例是基于機(jī)械的觀察。在這篇文章，我們討論一下目前所知道的以及我們對(duì)未來(lái)的展望。最后，表觀遺傳學(xué)的治療已經(jīng)被用于腫瘤學(xué)，也可能在自身免疫病的治療中有良好的作用。為何研究表觀遺傳學(xué)為何研究表觀遺傳學(xué)自身免疫病通常被認(rèn)為是一種復(fù)雜的疾病。遺傳背景使得人們對(duì)疾病有一定的易感性或抵抗性，但是它并不能成為疾病發(fā)展的使動(dòng)原因。許多發(fā)病時(shí)環(huán)境的相似性已經(jīng)證實(shí)了，但是自身免疫性疾病的病因還不為人們所知。全基因組關(guān)聯(lián)研究已經(jīng)證實(shí)了強(qiáng)烈的遺傳背景的存在，但是這個(gè)研究并沒(méi)有證實(shí)免疫耐受下降的單基因機(jī)制，并且強(qiáng)烈的基因關(guān)聯(lián)性也只在一小部分人中被證實(shí)。在同卵雙生子自身免疫性疾病的不完全共顯率強(qiáng)烈的支持其他補(bǔ)充機(jī)制可能涉及到基因表達(dá)的調(diào)節(jié)，最終導(dǎo)致自身免疫疾病?；谶@些觀察，用一些新的方法來(lái)分析組蛋白修飾和DNA甲基化支持了表觀遺傳學(xué)可能在引起自身免疫性疾病中起了重要的作用這一概念。表觀遺傳學(xué)研究的機(jī)制即決定和維持基因組的功能，不伴有DNA序列的改變。表觀遺傳基因組和表觀遺傳基因型被認(rèn)為是細(xì)胞通過(guò)表觀遺傳學(xué)機(jī)制誘導(dǎo)基因表大的特異的和穩(wěn)定的模式。在功能上，表觀遺傳學(xué)機(jī)制，確實(shí)在細(xì)胞分化過(guò)程中占重要的角色，它能夠誘導(dǎo)基因穩(wěn)定的表達(dá)和抑制。表觀遺傳學(xué)也能夠干預(yù)細(xì)胞的代謝，以此使細(xì)胞適應(yīng)周圍環(huán)境的改變。表觀遺傳學(xué)對(duì)環(huán)境和基因相互作用中扮演的角色，已經(jīng)在一些有趣的實(shí)驗(yàn)中證實(shí)，當(dāng)環(huán)境改變，會(huì)對(duì)基因表達(dá)產(chǎn)生修飾。首先，一項(xiàng)生殖的研究調(diào)查食物成分的改變對(duì)其影響，食物中富含甲基供體，為了改變懷孕刺鼠到的毛色，與喂養(yǎng)普通食物組對(duì)比，這些特殊食物所謂養(yǎng)出來(lái)的刺鼠后代毛色有特殊的改變。這個(gè)現(xiàn)象被證實(shí)有很明顯的DNA甲基化的改變，這就是非常徹底的表觀遺傳學(xué)的研究機(jī)制。這個(gè)過(guò)程是IAP逆轉(zhuǎn)錄病毒插入元件靜息，最終限制了刺鼠等位基因的表現(xiàn)。另一個(gè)典型的例子就是荷蘭人在二戰(zhàn)期間在子宮內(nèi)和兒童時(shí)期挨餓，對(duì)于胰島素樣生長(zhǎng)因子表達(dá)調(diào)節(jié)區(qū)DNA甲基化分析，證明暴露組與非暴露組相比存在一個(gè)高度保守的低甲基化狀態(tài)。最近的觀察研究已經(jīng)證實(shí)，DNA甲基化與一些遺傳因素有關(guān)，包括懷孕前吸煙，酒精攝入，環(huán)境污染物?；谶@些觀察，表觀遺傳學(xué)機(jī)制應(yīng)該被視為是環(huán)境和基因組作用的先驅(qū)。這樣就結(jié)合了那句老話“壞基因，壞運(yùn)氣”。這個(gè)被實(shí)驗(yàn)證據(jù)所支持，DRFRAGA和其同事證明了表觀遺傳學(xué)也許能夠解釋同卵雙生子自生免疫疾病非共顯率的問(wèn)題。隨著年齡的增長(zhǎng)，表型的異常顯著的增加，被稱為“表觀遺傳學(xué)流”，它是基于不同環(huán)境暴露所產(chǎn)生的。500個(gè)堿基對(duì)組成，CG的含量超過(guò)過(guò)55，CPG島有一個(gè)關(guān)鍵的調(diào)節(jié)功能，它存在于啟動(dòng)子區(qū)域并占了大部分的區(qū)域。改變CPG島的甲基化狀態(tài)，也許能改變?nèi)旧|(zhì)結(jié)構(gòu)，最終能調(diào)節(jié)啟動(dòng)轉(zhuǎn)錄因子與轉(zhuǎn)錄機(jī)制的相互作用。作為結(jié)果，在大多數(shù)的例子中，這種獲得性的和遺傳性的的甲基化狀態(tài)能夠?qū)е禄虮磉_(dá)的抑制，另外，CPG島甲基化狀態(tài)能與一種叫甲基CPG結(jié)合域的蛋白相互作用，盡管他們?cè)诓煌?xì)胞，不同位點(diǎn)的不同作用還不為大家所知，MBP蛋白被認(rèn)為通過(guò)結(jié)合甲基化的DNA來(lái)抑制基因的表達(dá)，這個(gè)過(guò)程將會(huì)導(dǎo)致染色質(zhì)的修飾和重塑。DNA甲基化在基因表達(dá)中的重要性，通過(guò)性染色體的平衡呈現(xiàn)出來(lái)，女性X染色體的轉(zhuǎn)錄被部分抑制，這個(gè)事實(shí)通過(guò)對(duì)特異性的序列甲基化來(lái)實(shí)現(xiàn)的。哺乳動(dòng)物的基因包含分散的基因簇，他從親代繼承的甲基化狀態(tài)決定了他某些特異性基因的表達(dá)機(jī)體繼承了這些表達(dá)了的或?yàn)楸磉_(dá)的富含CPG的基因序列，被稱為基因印跡。因此，這些基因印跡甲基化過(guò)程的錯(cuò)誤能夠使這些基因表達(dá)被繼承下來(lái)。從臨床的角度，DNA甲基化的重要性，尤其是甲基化損傷，是體現(xiàn)在兩個(gè)疾病，SILVERRUSSEL不對(duì)稱身材矮小性發(fā)育異常綜合征和BECKWITHWIEDEMANN。這兩種狀況都來(lái)自于11號(hào)染色體上基因印跡甲基化的錯(cuò)誤，這種錯(cuò)誤發(fā)生在編碼IGFF2以及母源基因表達(dá)（H19）。在生理情況系這些基因只在父源等位基因發(fā)生甲基化。BECKWITHWIEDEMANN綜合征由于父源母源的等位基因都發(fā)生甲基化而過(guò)多表達(dá)IGF2，然而，如果是這兩個(gè)印跡中心甲基化消失會(huì)導(dǎo)致IGF2位點(diǎn)的抑制以及H19表達(dá)增加最終導(dǎo)致SILVERRUSSEL綜合征。MICRORNAMICRORNA是翻譯后的調(diào)節(jié)因子，它涉及很多生理的過(guò)程，包括生長(zhǎng)，分化，增殖、凋亡。MIRNA是一個(gè)22NT長(zhǎng)非編碼RNA，他通過(guò)結(jié)合互補(bǔ)MRNA來(lái)抑制翻譯，并導(dǎo)致特定的RNA的降解。MIRNAS是基因編碼MRNA并且通過(guò)RNA聚合酶Ⅱ翻譯，與普通的編碼蛋白質(zhì)的RNA一樣，最近在自身免疫疾病和慢性炎癥中發(fā)現(xiàn)了他們。最著名的表觀遺傳學(xué)調(diào)節(jié)就是MIRNADNA相互作用，其代表就是女性X染色體的靜息。事實(shí)，兩條X染色體有一條在女性通過(guò)表觀遺傳學(xué)調(diào)節(jié)而處于靜息，導(dǎo)致X染色體的會(huì)存在劑量補(bǔ)償。這種平衡是通過(guò)X染色體靜息中心的X染色體靜息基因的轉(zhuǎn)錄來(lái)調(diào)節(jié)，這就使女性的基因表達(dá)與男性相適應(yīng)。XIST編碼一個(gè)非編碼MRNA包裝X染色體以此過(guò)程使得一大群在X染色體上的基因序列靜息。組蛋白抑制性標(biāo)記物和DNA甲基化是這種靜息變得很穩(wěn)定，因?yàn)檫@些發(fā)生在X染色體上表觀遺傳學(xué)的錯(cuò)誤能夠涉及到某些疾病的發(fā)病機(jī)制，包括自身免疫疾病。這確實(shí)是富有吸引人的假說(shuō)，這就能夠解釋某些自身免疫病女性占優(yōu)勢(shì)的原因。自身免疫疾病和表觀遺傳修飾自身免疫疾病和表觀遺傳修飾表觀遺傳學(xué)對(duì)在所有復(fù)雜疾病中的影響里在快速的提高，并很快會(huì)在我們對(duì)醫(yī)學(xué)的理解中占重要的地位，我們也許可以假想表觀遺傳學(xué)將填補(bǔ)在特定情況下疾病發(fā)病機(jī)制中關(guān)于基因和環(huán)境因素的之間關(guān)系的空白。在某些自身免疫性疾病，免疫細(xì)胞的表觀遺傳學(xué)調(diào)節(jié)過(guò)程中出現(xiàn)的特異性損害可能會(huì)導(dǎo)致免疫耐受下降，這個(gè)過(guò)程涉及到基因低甲基化和轉(zhuǎn)錄抑制。在自身免疫性疾病中，表觀遺傳學(xué)主要是通過(guò)人類外周血單核細(xì)胞核或用動(dòng)物模型來(lái)研究。在體和體外研究模型已經(jīng)證實(shí)，表觀基因組的變異也許可以導(dǎo)致自身反應(yīng)性T細(xì)胞克隆的發(fā)生，特異性的表觀遺傳學(xué)缺陷與某些自身免疫性疾病是有關(guān)的。例如，通過(guò)表觀遺傳學(xué)的調(diào)控，輔助性T細(xì)胞分化成TH1細(xì)胞亞群并產(chǎn)生IFN?并能夠?qū)辜?xì)菌，TH2細(xì)胞產(chǎn)生IL4和IL13。TH1細(xì)胞有的IFNΓ啟動(dòng)子區(qū)域去甲基化，

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簡(jiǎn)介：FULLTERMSNIELSENSU,AKIN,BROSSARD,SCHEUFELE,XENOS,2015FROMAWIDERANGEOFMETHODOLOGICALANDTHEORETICALTRADITIONSSCHOLARSHAVEPRODUCEDEXPANSIVEQUANTITATIVESTUDIESONTHETRENDSINMEDIACOVERAGEOFCLIMATECHANGEEG,UZELGUNCASTRO,2015,SUSTAINABLEFOODSYSTEMSLOCKIE,2006,ANDSUSTAINABILITYATLARGEBARKEMEYER,FIGGE,HOLT,WETTSTEIN,2009,WHEREASOTHERSHAVETAKENACRITICALPERSPECTIVEANDFOCUSEDQUALITATIVECRITIQUESONGENDEREDANDRACIALSTEREOTYPESPORTRAYEDINPOPULARFILMSABOUTCLIMATECHANGEANDSUSTAINABILITYEG,MCGREAVYLINDENFELD,2014ALTHOUGHTHISDIVERSEBODYOFMASSCOMMUNICATIONSCHOLARSHIPHASADVANCEDDISCIPLINARYUNDERSTANDINGOFMEDIATRENDSANDEFFECTS,ITOFTENTIMESFAILSTOENGAGEQUESTIONSABOUTWHAT,IFANYTHING,SHOULDBEDONETOCHANGETHESEDISCURSIVEPRODUCTIONSMASSCOMMUNICATIONRESEARCHISINHERENTLYASOCIALLYRELEVANTLINEOFRESEARCH,ANDWESEEKEYAREASOFGROWTHFORTHEFIELDININTEGRATINGMASSCOMMUNICATIONSCHOLARSHIPWITHRESEARCHBEINGDONEINTRANSDISCIPLINARYSUSTAINABILITYSCIENCETEAMSTHATAREFOCUSEDONSOLVINGPRESSINGSOCIETALPROBLEMSSUSTAINABILITYSCIENCEHASDEVELOPEDINANATTEMPTTOADDRESSSOCIETY’SMOSTCOMPLEXENVIRONMENTAL,ECONOMIC,ANDSOCIALPROBLEMS,ANDITCALLSFORANEWLEVELOFENGAGEMENTFROMACADEMICSANDCITIZENSALIKESUSTAINABILITYSCIENCEPOSITSTHATTRANSDISCIPLINARYTEAMSOFSCHOLARS,DECISIONMAKERS,ANDSTAKEHOLDERSFROMVARIOUSBACKGROUNDSCANPRODUCEMOREACTIONABLERESULTSTHANANYOFTHESE2SMITH,SULDOVSKY,LINDENFELDDOWNLOADEDBYAUSTRALIANNATIONALUNIVERSITYAT125504JUNE2016

簡(jiǎn)介：5300英文單詞，英文單詞，31500英文字符，中文英文字符，中文9900字文獻(xiàn)出處文獻(xiàn)出處SMITH,HOLLIE,BRIANNESULDOVSKY,ANDLAURALINDENFELD“MASSCOMMUNICATIONRESEARCHINSUSTAINABILITYSCIENCEMOVINGTOWARDANENGAGEDAPPROACHTOADDRESSSOCIETY’SSUSTAINABILITYDILEMMA“MASSCOMMUNICATIONANDSOCIETY1952016118MASSCOMMUNICATIONRESEARCHINSUSTAINABILITYSCIENCEMOVINGTOWARDANENGAGEDAPPROACHTOADDRESSSOCIETY’SSUSTAINABILITYDILEMMAHOLLIESMITHBRIANNESULDOVSKYLAURALINDENFELDMASSCOMMUNICATIONSCHOLARSHIPPROVIDESINVALUABLEINSIGHTINTOHOWDISCURSIVETRENDSINMEDIAREFLECT,PRODUCE,ANDOBSCURESOCIETY’SMOSTPRESSINGSUSTAINABILITYISSUES,YETTOOOFTENTHISRESEARCHFALLSSHORTOFCREATINGACTION,INTERVENTIONS,ORCHANGEINTHISARTICLE,WEARGUETHATMASSCOMMUNICATIONSHOULDBECONSIDEREDACORNERSTONEDISCIPLINEFORSUSTAINABILITYSCIENCERESEARCH,PARTICULARLYWITHINTRANSDISICIPLINARYSUSTAINABILITYSCIENCETEAMSWECONTENDTHATMASSCOMMUNICATIONRESEARCHERSCANADVANCESUSTAINABILITYEFFORTSBYMOVINGTOWARDAMOREENGAGEDAPPROACHINANEFFORTTOSUPPORTSCHOLARS’TRANSITIONTOSUCHENGAGEMENT,WECONSIDERHOWTRADITIONALMASSCOMMUNICATIONTHEORIESCANADDVALUETOACTIONORIENTEDTRANSDISCIPLINARYSUSTAINABILITYSCIENCEEFFORTSANDPROVIDEEXAMPLESOFENGAGED,TRANSDISCIPLINARYMASSCOMMUNICATIONSCHOLARSHIPINTRODUCTIONTHESPECIALCALLFORTHISISSUEOFMASSCOMMUNICATIONANDSOCIETYRAISEDAKEYQUESTIONWHATARETHEROLESOFMASSMEDIAANDOTHERFORMSOFCOMMUNICATIONWITHREGARDTOCLIMATEANDSUSTAINABILITYPROGRAMSTHISQUESTIONISPARTICULARLYRELEVANTGIVENTHERAPIDADVANCEMENTINGLOBALRISKSWEFACEASASOCIETYASWECONSIDERCOMMUNICATION’SROLEWITHINCLIMATEANDSUSTAINABILITYPROGRAMS,WEEXTENDTHISLINEOFQUESTIONINGTOREEVALUATETHEROLEOFMASSMEDIAANDCOMMUNICATIONRESEARCHERSWITHINSUSTAINABILITYRESEARCHANDPRACTICEASWELLMASSMEDIAANDCOMMUNICATIONSCHOLARSHAVELONGSTUDIEDSUSTAINABILITYISSUESEG,LEWIS,2000NIELSENSU,AKIN,BROSSARD,SCHEUFELE,WESEEMASSCOMMUNICATIONRESEARCHASAKEYPARTOFTHISEFFORTMASSCOMMUNICATIONSCHOLARSHIPISSOVASTLYIMPORTANTTOCOPRODUCTIONCORNWELLPOMERANZETAL,2014RAMACHANDRALEMOSPOHL,2008TRANSDISCIPLINARITYREQUIRESANITERATIVEAPPROACHTORESEARCH,WHERERESEARCHERSWORKBEYONDDISCIPLINARYBOUNDARIESTOENGAGESTAKEHOLDERSINTHECREATIONANDIMPLEMENTATIONOFRESEARCHBASEDPOLICIESANDPROJECTSKEYHEREISTHENEEDFORTHEMUTUALUNDERSTANDINGTHATDIVERSEKINDSOFKNOWLEDGEHAVEVALUEANDMUSTBEINCLUDEDINRESEARCHDESIGN,DATACOLLECTION,ANDKNOWLEDGEOUTCOMESWITHINTRANSDISCIPLINARYSUSTAINABILITYSCIENCE,RESEARCHERSHAVEONETYPEOFKNOWLEDGEANDSTAKEHOLDERSHAVEANOTHER,ANDBOTHHAVEEQUALVALUATIONINTHERESEARCHPROCESSANADóN,GIMéNEZ,BALLESTAR,HAGE,LEROY,DONK,METAG,KOHRIN,TEWKSBURYSCHEUFELE,2009,ANDCRITIQUESTEREOTYPICALPORTRAYALSOFMARGINALIZEDGROUPSMCGREAVYLINDENFELD,2015THESESTUDIESAREESSENTIALTOUNDERSTANDINGMEDIAPROCESSES,TRENDS,ANDEFFECTS,YETTHEYRELYONQUANTITATIVEANDQUALITATIVEANALYSISOFCOUNT,SURVEY,ORTHEMATICDATA,ANDRARELY,IFEVER,REQUIREENGAGEMENTWITHSCIENTISTSFROMOTHERDISCIPLINESORTHEDIRECTENGAGEMENTWITHHUMANSUBJECTSEVENMOREDISTINCTISTHELACKOFSTAKEHOLDERINCLUSIONINMASSCOMMUNICATIONRESEARCH,BEITTHEINCLUSIONOFLOCALMEDIACONSUMERS,JOURNALISTS,ORDIVERSEVOICESMASSCOMMUNICATIONRESEARCHERSNEEDTOBEINCLUDEDINTHESETRANSDISCIPLINARYEFFORTS,ASMEDIAEFFECTSTHEORIESOFFERACRUCIALUNDERSTANDINGOFISSUESTHATTHESETEAMSDEALWITHINALMOSTEVERYISSUEWHYPEOPLEPERCEIVESUSTAINABILITYISSUESINCERTAINWAYSANDWHATSHAPESTHEIRBEHAVIORINRESPONSEIFMASSCOMMUNICATIONTHEORIESAREIGNOREDINTHESUSTAINABILITYSCIENCEDESIGN,WERISKMISSINGANUNDERSTANDINGOFHOWMASSMEDIAPLAYAKEYROLEINCREATINGASHAREDCULTURALUNDERSTANDINGOFSUSTAINABILITYPHENOMENAINOURCOMMUNITIES,NATIONALLY,ANDGLOBALLYINCLUSIONINTHISIMPORTANTEFFORT,HOWEVER,DOESNOTJUSTMEANANSWERINGATRANSDISCIPLINARY

簡(jiǎn)介：THEEPIGENETICSOFAUTOIMMUNITYFRANCESCAMEDA1,2,MARCOFOLCI1,ANDREABACCARELLI3,ANDCARLOSELMI1,21DEPARTMENTOFMEDICINEANDHEPATOBILIARYIMMUNOPATHOLOGYUNIT,IRCCSISTITUTOCLINICOHUMANITAS,ROZZANO,MILAN,ITALY2DEPARTMENTOFTRANSLATIONALMEDICINE,UNIVERSITYOFMILAN,ROZZANO,MILAN,ITALY3HARVARDSCHOOLOFPUBLICHEALTH,EXPOSURE,EPIDEMIOLOGYTEL390282245129FAX390282244590CARLOSELMIUNIMIITNIHPUBLICACCESSAUTHORMANUSCRIPTCELLMOLIMMUNOLAUTHORMANUSCRIPTAVAILABLEINPMC2011MAY13PUBLISHEDINFINALEDITEDFORMASCELLMOLIMMUNOL2011MAY83226–236DOI101038/CMI201078NIHPAAUTHORMANUSCRIPTNIHPAAUTHORMANUSCRIPTNIHPAAUTHORMANUSCRIPTEPIGENETICCHANGESKNOWNSOFAR,ANDTHEREFORETHEIRUNDERLYINGPROCESSESWILLBEDISCUSSEDBELOWINFURTHERDETAILSMOREOVER,THENEWESTFIELDOFMICRORNAWILLBEBRIEFLYILLUSTRATEDASANADDITIONALGENEREGULATORYMECHANISMHISTONEMODIFICATIONSASMENTIONEDBEFORE,HISTONESAREHIGHLYCONSERVEDPROTEINSTHATRESIDEWITHINNUCLEIOFEUKARYOTICCELLSTHEYCANBECLASSIFIEDINTOTWOMAINGROUPS1COREHISTONESH2A,H2B,H3,ANDH4THATAREPARTOFTHENUCLEOSOMECORE,THEBASICUNITOFDNAPACKAGINGINEUKARYOTICS,AND2LINKERHISTONESH1,H5TWOOFEACHOFTHECOREHISTONESASSEMBLETOFORMANOCTAMERICNUCLEOSOMECOREPARTICLEBYWRAPPINGABOUT147BASEPAIRSOFDNAAROUNDTHEPROTEINSPOOLINA17LEFTHANDEDSUPERHELICALTURN9FIGURE1,THUSPROVIDINGDNACONDENSATIONANDORGANIZATIONINTHENUCLEUS,ASWELLASMODULATINGDNAACCESSIBILITYTOTHETRANSCRIPTIONMACHINERYTHISLATTERPROCESSCOULDBEREPRESENTEDASADRAWERTHATCANBEOPENEDORCLOSEDFOLLOWINGSPECIFICSTIMULIINFACT,EACHHISTONESUBTYPECANBEMODIFIEDBYDIFFERENTCHEMICALMODIFICATIONATDEFINEDAMINOACIDSLEADINGTOTRANSCRIPTIONMODULATIONAND,THEREFORE,CELLCYCLEREGULATION,DEVELOPMENT,ANDDIFFERENTIATIONEACHOFTHEFOURCOREHISTONESSHARESTHESAMEFOLDINGSTRUCTUREKNOWNASHISTONEFOLDDOMAINHFD,WHICHCONSISTSOFTHREEΑHELICESΑ1,Α2,ANDΑ3SEPARATEDBYTWOLOOPSL1ANDL210THEHFDFOLDTOGETHERINANTIPARALLELPAIRSH3WITHH4ANDH2AWITHH2BTOCONSTITUTETETRAMERSTHESUBSEQUENTASSEMBLYOFTWOTETRAMERSFORMSTHEOCTAMERICCORESTRUCTUREH3/H4H2A/H2B1OFTHENUCLEOSOME11THENTERMINALREGIONSOFHISTONESPROTRUDEOUTSIDETHENUCLEOSOMECOREANDAREPRONETOPOSTTRANSLATIONALMODIFICATIONS,WHICHAREIMPORTANTINCHROMATINCOMPACTIONANDGENEREGULATIONHISTONEPOSTTRANSLATIONALMODIFICATIONSCONCURTODETERMINETHEPATTERNDEFINEDAS“HISTONECODE”ANDWILLBESUMMARIZEDBELOWALLTHESEHISTONEMODIFICATIONSARECAUSEDBYSPECIFICENZYMESWHICHRECOGNIZEHISTONETAILSANDCANWORKTOADDORREMOVEFUNCTIONALGROUPSWHICHAREINTURNRECOGNIZEDBYNUCLEARFACTORSSPECIFICPROTEINSHAVEAFFINITYFORMODIFIEDAMINOACIDRESIDUESFORINSTANCEBROMODOMAINSBINDACETYLATEDLYSINESORCHROMODOMAINSMETHYLATEDLYSINESANDPROMOTESPECIFICCHANGESINCHROMATINDETERMININGRESPECTIVELYTHEACTIVATIONORTHESILENCINGOFGENETRANSCRIPTIONFIGURE2AMONGHISTONEMODIFICATIONS,ACETYLATIONORDEACETYLATIONAREONEOFTHEMOSTIMPORTANTGENEEXPRESSIONREGULATORYMECHANISMSTHESEPROCESSESINVOLVESELECTEDLYSINERESIDUESINTHETAILSOFNUCLEOSOMALHISTONESANDAREINDUCEDBYHISTONEACETYLTRANSFERASEHATANDHISTONEDEACETYLASEHDACENZYMES,RESPECTIVELY12–15HATENZYMESSHARETHEABILITYTOPROMOTEGENEEXPRESSIONBYTRANSFERRINGACETYLGROUPSTOLYSINE16–18WHILEHDACSREMOVEACETYLGROUPSANDGENERALLYASSOCIATEWITHGENEREPRESSION19–21ASECONDMECHANISMINVOLVESHISTONEMETHYLATIONANDITSEFFECTSDEPENDONTHEPOSITIONOFTHEMODIFIEDLYSINERESIDUEWITHINTHEHISTONETAILANDONTHENUMBEROFMETHYLGROUPSADDEDTOSUCHRESIDUESASANEXAMPLE,THEPRESENCEOFTHREEMETHYLGROUPSONLYSINE4RESIDUEONHISTONEH3MEH3K4,HASBEENASSOCIATEDWITHTRANSCRIPTIONALACTIVATIONWHEREASTHETRIPLEMETHYLATIONOFRESIDUES9OR27DETERMINESREPRESSION3,22–26ASATHIRDMECHANISM,ARGININECANALSOBEMETHYLATED/DEMETHYLATEDBYSPECIFICENZYMESANDPLAYACRITICALROLEINTHEDYNAMICREGULATIONOFGENEEXPRESSION27METHYLATIONOFARGININERESIDUE3ONHISTONEH4H4R3ANDARGININE17ONHISTONEH3H3R17HAVEBEENSHOWNTOINDUCEGENEACTIVATION23,28–30FINALLY,UBIQUITINISA76AMINOACIDPROTEINTHATISINVOLVEDINSPECIFICPROTEINLABELINGUBIQUITINATEDPROTEINSARECOMMITTEDTOPROTEOSOMALDEGRADATIONANDUBIQUITINATIONTHUSCONTROLLINGTHESTABILITYANDINTRACELLULARLOCALIZATIONOFNUMEROUSPROTEINSUBIQUITINATIONULTIMATELYINFLUENCESTHESTATUSOFHISTONESMETHYLATIONORMEDAETALPAGE3CELLMOLIMMUNOLAUTHORMANUSCRIPTAVAILABLEINPMC2011MAY13NIHPAAUTHORMANUSCRIPTNIHPAAUTHORMANUSCRIPTNIHPAAUTHORMANUSCRIPT

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簡(jiǎn)介：23519789?2015PUBLISHEDBYELSEVIERBVTHISISANOPENACCESSARTICLEUNDERTHECCBYNCNDLICENSEHTTP//CREATIVECOMMONSORG/LICENSES/BYNCND/40/PEERREVIEWUNDERRESPONSIBILITYOFAHFECONFERENCEDOI101016/JPROMFG201507931PROCEDIAMANUFACTURING320156483–6489AVAILABLEONLINEATWWWSCIENCEDIRECTCOMSCIENCEDIRECT6THINTERNATIONALCONFERENCEONAPPLIEDHUMANFACTORSANDERGONOMICSAHFE2015ANDTHEAFFILIATEDCONFERENCES,AHFE2015CONTRIBUTIONSOFERGONOMICSTOANAFFECTIVESUSTAINABILITYINCHILDREN’SFURNITURECRISTINASALVADORCENTRODEINVESTIGA??OEMARQUITECTURA,URBANISMOEDESIGN,FACULDADEDEARQUITECTURADAUNIVERSIDADEDELISBOA,RUASáNOGUEIRA,PóLOUNIVERSITáRIO,ALTODAAJUDA,1349055LISBOA,PORTUGALABSTRACTWITHINTHECONTEXTOFANINVESTIGATIONINPRODUCTDESIGN,FOCUSINGONCHILDREN’SFURNITUREHIGHCHAIRS,ARESEARCHWASMADE,DEALINGWITHISSUESASAFFECTIVESUSTAINABILITY,LEADINGTOWASTEREDUCTIONANDPRODUCTOPTIMIZATIONTHECHILDISASPECIALTARGET,SINCETHENEEDOFAFFECTIONANDSUPPORTANDTHEPOTENTIALINTENSITYOFEMOTIONALBONDSAREHIGHLYPRESENTINTHISEARLYSTAGEOFHUMANDEVELOPMENTALONGWITHLITERARYREVIEW,THEUSEOFERGONOMICSANDHUMANFACTORSASATOOL,INORDERTOOBSERVEANDANALYZECHILDREN’SBEHAVIORTOWARDSSPECIFICTYPESOFFURNITURETHROUGHANINTERVIEWBASEDSTUDY,MAYCONTRIBUTETOABIGGERUNDERSTANDINGOFWHATENABLESANEMOTIONALCONNECTIONBETWEENSUBJECTANDOBJECTANDWHATARETHEIRPARENTS’CHOICESBASEDONERGONOMICSMAYBEANESSENTIALKEYTOTHISUNDERSTANDING,ASITHELPSUNRAVELHOWHUMANSINTERACTWITHTHEIRSURROUNDINGSINAFULLEXTENT,BOTHPHYSICALLYANDPSYCHOLOGICALLYCONCLUSIONSMAYNOTRESULTINAMAGICFORMULAINORDERTOCREATESUPEROBJECTS,WHICHEVERYCHILDRENWOULDWANTANDLOVE,BUTATLEASTGIVESABETTERUNDERSTANDINGONHOWSENSITIVEANDSUBJECTIVECHILD’SATTACHMENTTOOBJECTSCANBEANDHOWDECISIVECANERGONOMICSBEINTHERESEARCHPROCESSFORADESIGNPROJECT?2015THEAUTHORSPUBLISHEDBYELSEVIERBVPEERREVIEWUNDERRESPONSIBILITYOFAHFECONFERENCEKEYWORDSERGONOMICSANDHUMANFACTORSPRODUCTDESIGNCHILDREN’SFURNITUREAFFECTIVESUSTAINABILITYCORRESPONDINGAUTHORTEL351213615000FAX351213615001EMAILADDRESSCRISTINASALVADORFAULISBOAPT?2015PUBLISHEDBYELSEVIERBVTHISISANOPENACCESSARTICLEUNDERTHECCBYNCNDLICENSEHTTP//CREATIVECOMMONSORG/LICENSES/BYNCND/40/PEERREVIEWUNDERRESPONSIBILITYOFAHFECONFERENCE6485CRISTINASALVADOR/PROCEDIAMANUFACTURING320156483–6489TABLE1INTERVIEWQUESTIONSACHILDREN’SCHAIR01DOYOUHAVEONEORMORECHILDREN’SHIGHCHAIRS02WHATARETHEBRAND,MODELANDCOLOR03THEACQUISITIONWASON1STOR2NDHAND04WHATWERETHEFEATURESTHATINFLUENCEDYOURCHOICE05DIDTHECHAIRREQUIRESPECIALMAINTENANCE06CANYOUDESCRIBETECHNICALOROTHERPROBLEMSTHATHAVEBEENIDENTIFIED07HOWWOULDYOUDESCRIBEITSPERFORMANCEINTERMSOFENDURANCEANDEFFICIENCYBADAPTATION08THECHILDRECEIVEDTHECHAIRATWHATAGE09HOWOLDISTHECHILD10DIDTHECHILDEXPERIENCETHECHAIRBEFORETHEACQUISITION11WHATWASHER/HISFIRSTREACTION12HOWWASTHEADAPTATION13WERETHEREANYFALLS,INSTABILITYORMISUSEBYTHECHILD14DOESTHECHILDIDENTIFYTHECHAIRASHER/HISOWN15DOESSHE/HESEEMSTOHAVECREATEDEMOTIONALTIESWITHTHEOBJECT16DOESSHE/HECOMPLAINWHENSOMEBODYTRIESTOSITONTHECHAIR17DIDSHE/HETRYTOCUSTOMIZETHECHAIRWITHDRAWINGSORSTICKERSCUSE18THECHAIRISUSEDFORWHATKINDOFACTIVITIES19HOWLONGWILLTHECHILDBESEATEDDURINGONEOFTHESEACTIVITIES20DOESSHE/HENEEDSECURITYSYSTEMS21DOESTHECHILDMANAGETOSITALONE22DOESSHE/HEHAVETOBEFORCEDTOSIT23ISTHECHILDCOMFORTABLEORCOMPLAINSSHE/HEWANTSTOGETOUT24DOESTHECHILDFALLASLEEPONTHECHAIR25ISITEASYTOCLEANONADAILYBASISDCONCLUSION26BASEDONTHECHAIR’SPERFORMANCE,WOULDYOURECOMMENDIT27INCASEITISANEVOLUTIVECHAIRTHATFOLLOWSCHILD’SGROWTH,DOYOUINTENDTOKEEPIT28INCASEITISNOTANEVOLUTIVECHAIR,AFTERTHECHILDIS23YEARSOLD,DOYOUINTENDTOREPLACEITBYACHAIRFORADULTS29DOYOUHAVEANYFURTHERCOMMENTSABOUTTHECHAIR22RESULTSRESULTSOFTHEINTERVIEWSARESUMMARIZEDIN4TABLESTABLE2WITHRESULTSABOUTTHEPARENT’SCHOICEANDACQUISITION,PROBLEMSIDENTIFIEDANDAPPRECIATIONINTERMSOFEFFICIENCYTABLE3WITHRESULTSABOUTTHECHILDREN’SEMOTIONALRESPONSETOTHEPRODUCTTABLE4WITHTHERESULTSABOUTTHECHILDREN’SUSEOFTHEPRODUCTTABLE5WITHRESULTSABOUTPARENTS’SATISFACTIONANDINTENTIONSFORTHEPRODUCT’SFUTURETHESAMPLEOF26HIGHCHAIRSFORCHILDRENWASEVENLYDIVIDEDBETWEENTWOTYPESOFCHAIRS–THECHAIRSTHATCANFOLLOWCHILD’SGROWTHUNTILADULTHOODANDTHEONESTHATCAN’TTRIPPTRAPP?CHAIRFROMSTOKKE?,DESIGNEDBYPETEROPSVIK,WHOSEWORKDESERVEDFURTHERRESEARCHINPREVIOUSSTUDIESBYTHEAUTHOR12,REPRESENTS50OFTHESAMPLEPOLLYCHAIRFROMCHICCO?REPRESENTS38,5ANDANTILOPCHAIRFROMIKEA?REPRESENTSTHEREMAINING11,5OFTHESAMPLETHEACQUISITIONISMOSTLYIN1STHANDANDTHEFEATURESORFACTORSTHATINFLUENCEDTHECHOICEAREVARIABLEPARENTSWHOCHOOSETRIPPTRAPP?CHAIRSAREMORECONCERNEDWITHDURABILITY,CLASSICTIMELESSDESIGN,QUALITY,BRAND,SAFETYANDECOLOGYINWHATSEEMSTOBEAMORESUSTAINABLEPRODUCTIMAGES,FROMEACHMODELINTHEIRUSERSHOME,CANBESEENINFIG1A,BANDC