RANKL poolt indutseeritud transkriptsioonifaktorite tuvastamine tüümuse epiteelis

Ligipääs piiratud kuni 01.01.20162016-01-0

Jaapani keele tõlkimise probleemid Otsuichi lühijuttude "Õnn on kassipoja kujuline" ja "Hidamari no shi" näitel

Käesoleva magistritöö teema on kahe Otsuichi (kodanikunimega Hirotaka Adachi) lühijutu – „Õnn on kassipoja kujuline“ ja „Hidamari no shi“ tõlge eesti keelde ja nende tõlgete analüüs. Analüüsi osa on jaotatud laialt kolme osasse – probleemid, mis puudutasid keelt grammatika tasemel, probleemid keele eripära tasemel ning ka küsimused, mis puudutasid jaapani kultuuriruumile omaste terminite tõlget või siis tõlkimata jätmist. Üks läbivatest teemadest oli ka see, kui palju silmnähtavalt peent, kuid tegelikult sügavat sisu kandvaid detaile peavad minema eesti keelde tõlkides kaotsi.http://www.ester.ee/record=b4606079*es

Canonical notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). However, the mechanisms controlling cTEC and mTEC production from the common TEPC are not understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPCs at the expense of cTEC differentiation. Finally, we uncover a cross-regulatory relationship between NOTCH and FOXN1, a master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development, and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo

TNF perekond ja AIRE tüümuse diferentseerumise ja Candida albicans-vastase kaitse ristteedel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneT-rakkude koordineeritud küpsemine tüümuses on üks kesksetest moodustest, millega hoitakse ära autoimmuunsust. Seal õpetatakse lümfotsüütidele vahet tegema kehaomastel ja võõrastel antigeenidel. Antud protsess on suuresti kontrollitud tüümuse säsi epiteelirakkude (mTEC – medullary thymic epithelial cells) poolt, mis esitavad arenevatele T-rakkudele suurt hulka koespetsiifilisi antigeene, millest paljude ekspressioon on kontrollitud Autoimmuunregulaatori (AIRE) geeni poolt. AIRE puudulikkus põhjustab inimestel APECED-i (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy), haigust, mida iseloomustavad krooniline kandidoos, autoimmuunrünnakud sisenõrenäärmete vastu ja autoantikehad, mis neutraliseerivad mitmeid põletikulisi tsütokiine. mTEC-id ekspresseerivad AIRE-t ja seega suudavad täismahus koordineerida T-rakkude diferentseerumist ainult teatud küpsusastmes, mistõttu on tarvis uurida nende rakkude talitlust, AIRE ekspressiooni kontrollivaid mehhanisme ja erinevate APECED-i aspektide rolle haiguse sümptomaatika väljakujunemises. Käesolevas väitekirjas on kirjeldatud olulisemaid tüümuse epiteelirakkude küpsemist suunavaid transkriptsioonilisi mehhanisme ning uuritud lähemalt signaalradu, mis kontrollivad AIRE aktivatsiooni. Leiti, et signaaliedastus läbi NF-кB retseptori aktivaatori (RANK - receptor activator of NF-κB) aktiveerib vahetult AIRE ekspressiooni läbi kanoonilise NF-κB raja ning et AIRE mängib olulist rolli mTEC-ide küpsemise suunamises, mille lõpus muunduvad mTEC-id keratiniseerunud Hassall’i kehadeks. Samuti hinnati osade APECED-i patsientides leiduvate autoantikehade võimet esile kutsuda kandidoosi. Leiti, et neutraliseerivad autoantikehad IL-22 vastu võivad potentsiaalselt olla eelsoodumusteguriks Candida infektsioonile. Kokkuvõttes avardab antud väitekiri meie teadmisi võtmemehhanismidest, mis reguleerivad erinevaid protsesse tüümuses ja on keskse tähtsusega immuuntolerantsi väljakujunemiseks.One of the key mechanisms of preventing autoimmunity is the coordinated development of T-cells in the thymus, where developing lymphocytes are taught to differentiate between self and non-self. This process is largely under the control of medullary thymic epithelial cells (mTECs), which present developing T-cells with a wide array of otherwise tissue specific antigens, a large number of which are under transcriptional control of Autoimmune Regulator (AIRE). AIRE deficiency in humans leads to APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy), a disease characterized by candidiasis, autoimmune attacks against multiple endocrine organs and autoantibodies against multiple inflammatory cytokines. Since mTECs express AIRE and are thus capable of facilitating proper T-cell development only in a short maturation window, it is necessary to understand how these cells function, what are the underlying mechanisms regulating AIRE expression as well as the pathogenic potential of various aspects of APECED. This thesis describes the key transcriptional networks associated with thymic epithelial cell functions necessary for the establishment of the thymic microenvironment and explores in detail the activation principles of AIRE in the thymic epithelium. It was determined that signalling through receptor activator of nuclear factor kappa-B (RANK) directly induces AIRE expression through the activation of the canonical NF-κB pathway and that AIRE plays an important role in coordinating the mTEC maturation process, which ends in the formation of Hassall’s corpuscles. The potential of autoantibodies against cytokines found in APECED patients to precipitate Candida infections were also assessed, where it was found that neutralizing autoantibodies against IL-22 could act as a susceptibility factor for candidiasis. All in all, this thesis expands our knowledge of the key mechanisms that regulate thymic processes central to the formation of immune tolerance

Temporal regulation of terpene synthase gene expression in Eucalyptus globulus leaves upon ozone and wounding stresses: relationships with stomatal ozone uptake and emission responses

© 2018 Elsevier B.V. Ozone and wounding are key abiotic factors but, their interactive effects on temporal changes in terpene synthase gene expression and emission responses are poorly understood. Here, we applied combined acute ozone and wounding stresses to the constitutive isoprenoid-emitter Eucalyptus globulus and studied how isoprene, 1,8-cineole, and isoledene synthase genes were regulated, and how the gene expression was associated with temporal changes in photosynthetic characteristics, product emission rates, and stomatal ozone uptake through recovery phase. Photosynthetic characteristics and emission rate of isoprene, 1,8-cineole, and isoledene were synergistically altered, while three TPS gene expressions were antagonistically altered by combined stress applications. A time-delay analysis indicated that the best correspondences between gene expression and product emission rates were observed for 0 h time-shift for wounding and 0–2 h time-shifts for separate ozone, and combined ozone and wounding treatments. The best correspondence between ozone uptake and gene expression was observed for 0–4 h time-shifts for separate ozone and combined ozone and wounding treatments. Overall, this study demonstrated that expression profiles of isoprene, the monoterpene 1,8-cineole, and the sesquiterpene isoledene synthase genes differentially influenced their corresponding product emissions for separate and combined ozone and wounding treatments through recovery