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[{"key": "dc.contributor.advisor", "value": "Laajala, Mira", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Marjom\u00e4ki, Varpu", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Aspelin, William", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2020-01-27T07:06:46Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2020-01-27T07:06:46Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2019", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/67530", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Is\u00e4nt\u00e4solut ovat kehitt\u00e4neet useita keinoja tunnistaa viruksia ja est\u00e4\u00e4 niiden lis\u00e4\u00e4ntyminen. Yksi n\u00e4ist\u00e4 keinoista on translaatioon vaadittavan tukiproteiini eukaryotic intiation factor 2:n (eIF2) fosforylaatio, joka est\u00e4\u00e4 translaation tehokkaasti. Kaksijuosteisesta RNA:a (dsRNA) aktivoituva protein kinase dsRNA-dependent-proteiini (PKR) on eIF2 kinaasi, joka itsefosforyloituu aktivoituessaan. Sek\u00e4 PKR:N ett\u00e4 eIF2:n fosforylaatio yhdistet\u00e4\u00e4n usein antiviraaliseen soluviestint\u00e4\u00e4n. Echovirus 1 (EV1) kuuluu enterovirusten B-alaryhm\u00e4\u00e4n, jonka j\u00e4senist\u00e4 useat on yhdistetty tyypin 1 diabeteksen puhkeamiseen sille altistuneissa lapsissa. Se tunkeutuu is\u00e4nt\u00e4soluihin endosominkaltaisissa rakkuloissa ja vapauttaa genominsa proteiinikuoresta n\u00e4iss\u00e4 rakkuloissa. Ei ole t\u00e4ysin varmaa miten EV1 genomi p\u00e4\u00e4see rakkulakalvon l\u00e4pi solulimaan, jossa translaatio ja replikaatio tapahtuvat. T\u00e4ss\u00e4 ty\u00f6ss\u00e4 osoitamme, ett\u00e4 EV1-infektoituihin soluihin transfektoidut virusgenomille komplementaariset oligonukleotidikoettimet aktivoivat PKR:n fosforylaatiota muodostaessaan kompleksin virusgenomin kanssa solulimassa. T\u00e4t\u00e4 fosforylaatiota voi k\u00e4ytt\u00e4\u00e4 osoittamaan, ett\u00e4 EV1 genomi on vapautunut endosomirakkulasta solulimaan, mik\u00e4 tapahtui A549 soluissa noin 2,5\u22123,5 tuntia infektion j\u00e4lkeen. Pidemm\u00e4lle kehitettyn\u00e4 t\u00e4m\u00e4 uusi metodi voi tulevaisuudessa auttaa selvitt\u00e4m\u00e4\u00e4n, miten EV1:n genomi vapautuu endosomista, l\u00f6yt\u00e4m\u00e4\u00e4n siihen liittyvi\u00e4 proteiineja sek\u00e4 kehitt\u00e4m\u00e4\u00e4n l\u00e4\u00e4kkeit\u00e4 ja rokotteita EV1:\u00e4 vastaan.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Pathogens may trigger various antiviral responses in eukaryotic cells. One such response is preventing viral translation by eukaryotic initiation factor 2 (eIF2) phosphorylation. Protein kinase double-stranded RNA-dependent (PKR) is an eIF2 kinase activated by phosphorylation after exposure to double-stranded RNA (dsRNA). Though they act as hub elements for several stress signalling pathways, PKR and eIF2 phosphorylation is strongly associated with antiviral responses. Echovirus 1 (EV1) belongs to the enterovirus subgroup B, many members of which have been implicated in the development of type 1 diabetes in individuals exposed to the virus as infants, sparking interest in their biology and the development of drugs and vaccines. The major entry route of EV1 is via endosomal-like vesicles in which the uncoating of the genome occurs. How and when echoviral genomes cross this membrane barrier to the cytoplasm is not well known. Here we demonstrate that the phosphorylation of PKR can be induced by dsRNA composed of released EV1 genomes and transfected oligonucleotide probes. Furthermore, this phosphorylation can be detected by Western blot and used to demonstrate that echovirus 1 genomes cross the endosomal membrane barrier approximately 2.5\u22123.5 hours post-infection in A549 cells. If developed further, this new method may help characterise the mechanism of endosomal egress and any proteins involved as well as provide a tool for anti-echoviral drug and vaccine development.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2020-01-27T07:06:46Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2020-01-27T07:06:46Z (GMT). No. of bitstreams: 0\n Previous issue date: 2019", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "47", "language": "", "element": "format", "qualifier": "extent", "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": "eIF2", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "kinase", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "oligonucleotide", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "stress", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "timeline", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "translation", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "PKR phosphorylation as an Indicator for echovirus 1 genome egress from endosomes", "language": "", "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-202001271794", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "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": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "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": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "virukset", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "RNA", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "perim\u00e4", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "molekyylibiologia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "solubiologia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteiinit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "infektiot", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "fosforylaatio", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "viruses", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "RNA", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "genome", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "molecular biology", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "cell biology", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteins", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "infections", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "phosphorylation", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}]
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