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[{"key": "dc.contributor.author", "value": "Laitalainen, Jarkko", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2014-01-04T11:35:03Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2014-01-04T11:35:03Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2013", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1290783", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/42755", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Soluspesifinen geenien ilmentyminen on molekyylibiologian yksi suurista tutkimusalueista. Geenit aktivoituvat eri solutyypeiss\u00e4 eri tavoin, vaikka soluissa on sama geneettinen perim\u00e4. Tutkimuksissa on l\u00f6ydetty useita tekij\u00f6it\u00e4 mm. enhanserit ja enhanseri-RNA molekyylit, jotka vaikuttavat mm. solukohtaiseen geenin ilmentymiseen. Enhanserit ovat alueita genomissa, jotka sitovat proteiineja ja vuorovaikuttavat transkriptiokompleksin kanssa lis\u00e4ten geenin transkriptiota. Enhanseri-RNA:t ovat enhaserialueilta tuottettuja RNA-molekyylej\u00e4. Geenin ilmentymiseen vaikuttaa todella moniulotteinen s\u00e4\u00e4telyj\u00e4rjestelm\u00e4, kun mukaan lasketaan kaikki transkriptioon ja translaatioon vaikuttavat tekij\u00e4t.\n\nEndoteelisolut ovat veri- ja imusuonten sein\u00e4mien soluja, jotka muodostavat ohuen kerroksen suonten sis\u00e4pinnalle. Solukerroksen teht\u00e4v\u00e4 on s\u00e4\u00e4dell\u00e4 mm. nesteiden ja ravinteiden p\u00e4\u00e4sy\u00e4 suonesta ymp\u00e4r\u00f6iv\u00e4\u00e4n kudokseen. Endoteelisolut ovat my\u00f6s suuressa roolissa uusien verisuonten muodostumisessa niin normaalioloissa kuin sy\u00f6viss\u00e4kin. Hypoksia on er\u00e4s tekij\u00e4, joka aktivoi verisuonten muodostumista endoteelisoluista. Hypoksia on fysiologinen tila, jossa solu, kudos tai koko keho k\u00e4rsii hapen puutteesta. Hypoksia johtaa vakavimmillaan hapenpuutteesta k\u00e4rsiv\u00e4n kudoksen kuolemaan eli nekroosiin. Hypoksia voi muodostua, mik\u00e4li verenkierto h\u00e4iriintyy esim. verisuonen tukkeuman tms. takia eik\u00e4 veri kulkeudu normaalisti kudokseen.\n\nTy\u00f6n tarkoitus oli luoda endoteelispesifisi\u00e4 hypoksia-aktivoituvia vektoreita. Genomista valittiin yksi promoottori, kolme enhanseria ja kolme 3\u2019-UTR-aluetta. Alueet kloonattiin napanuoran verisuonten endoteelisoluista (HUVEC) eristetyst\u00e4 genomista ja liitettiin pGL4.10 pohjaisiin lusiferaasi-vektoreihin. Tuotetut konstruktit transfektoitiin viiteen solulinjaan, joista kaksi oli endoteelisolulinjoja. Transfektion j\u00e4lkeen soluja kasvatettiin 24 tuntia normaalissa happipitoisuudessa tai 1%-hypoksiassa. K\u00e4sittelyiden j\u00e4lkeen konstruktien lusiferaasi-aktiivisuus mitattiin soluista ja aktiivisuuksia vertailtiin kesken\u00e4\u00e4n.\n\nTulokset osoittavat soluspesifisyyden ja hypoksia-aktivoitumisen olevan monen eri tekij\u00e4n summa. Geenin ilmentyminen oli suurempaa kahdella konstruktilla kahdessa solulinjassa verrattuna kontrolleihin. Konstruktien luciferaasi-geeni aktivoitui endoteelisoluissa, mutta my\u00f6s muissa solulinjoissa. Hypoksia-aktivoitumisesta oli tilastollisesti merkitt\u00e4vi\u00e4 tuloksia yhden konstruktin kohdalla, joskin rohkaisevia tuloksia saatiin my\u00f6s muilla konstrukteilla.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Cell specific gene expression is one of the most interesting fields in molecular biology. Genes are expressed differently in different cell types even the cells have same genetic material. Studies have found multiple factors affecting cell specific gene expression, enhancer regions and enhancer-RNA (eRNA) molecules among other things. Enhancers are DNA regions that can bind transcription factors and then interact with transcription complexes enhancing the expression. eRNAs are RNA-molecules transcribed from the enhancer regions. Cell specific gene expression is a complex system when all factors affecting transcription and translation are counted in.\n\nEndothelial cells are a thin layer of cells in blood- and lymphatic vessel walls. Main functions of endothelial cells are to regulate access of fluids and nutrients from vessels to the surrounding tissues. Endothelial cells play also a critical role in angiogenesis in normal situations and also in cancers and in cardiovascular diseases. Hypoxia is one factor that can activate angiogenesis. Hypoxia is a physiological condition where a cell, a tissue or the whole body is lacking oxygen. It can lead to cell deaths or even tissue necrosis. Hypoxia can be formed when blood circulation is disturbed for example by partial blockage of a blood vessel so that blood cannot flow freely.\n\nThe aim of this study was to produce endothelial-specific hypoxia-regulated vectors. One promoter-, three enhancer- and three 3\u2019UTR-regions were selected to be cloned from the genome of human umbilical vein endothelial cells (HUVEC). Cloned regions were inserted into pGL4.10 based vectors containing luciferase gene. The constructs were transfected into five cell lines where two of them were endothelial cells. After transfection cells were subjected to normoxia or 1%-hypoxia. After the treatments luciferase activities were measured and compared.\n\nResults indicate that cell specific gene expression and enhancing is sum of a multiple factors. Gene expressions were higher with two of the constructs compared to the controls. All constructs expressed luciferase in endothelial cells but also in other cell types. One construct showed statistically significant hypoxia activation and the other constructs gave promising results of hypoxia activation.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Jarkko Laitalainen (jarjuhla) on 2014-01-04 11:35:03.004087. Form: Pro gradu -lomake (1 tekij\u00e4) (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake-1-tekijae). JyX data:", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by jyx lomake-julkaisija (jyx-julkaisija@noreply.fi) on 2014-01-04T11:35:03Z\nNo. of bitstreams: 2\nURN:NBN:fi:jyu-201401041022.pdf: 969869 bytes, checksum: 9f97a99d1a4937701a003f454dda6365 (MD5)\nlicense.html: 4904 bytes, checksum: d8f5f0afb253e48a30b862b8d5247e9c (MD5)", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2014-01-04T11:35:03Z (GMT). No. of bitstreams: 2\nURN:NBN:fi:jyu-201401041022.pdf: 969869 bytes, checksum: 9f97a99d1a4937701a003f454dda6365 (MD5)\nlicense.html: 4904 bytes, checksum: d8f5f0afb253e48a30b862b8d5247e9c (MD5)\n Previous issue date: 2013", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (40 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "hypoxia", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "endothelial cells", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "promoter", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "enhancer", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "UTR", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "gene therapy", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Constructing endothelial-specific hypoxia-regulated vectors", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201401041022", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.date.updated", "value": "2014-01-04T11:35:04Z", "language": null, "element": "date", "qualifier": "updated", "schema": "dc"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": 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