Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "August 2007" Includes bibliographical references.

Thesis (Ph.D. in Microbiology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 198-225). Online version available via ProQuest Digital Dissertations.

Thesis (Ph.D. in Microbiology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 126-147). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Thesis (Ph.D. in Biochemistry) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 191-200). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 98-115).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 101-121).

Bibliographische Beschreibung cand. med. Anton Brosig Regulation der Genexpression durch virale RNA und viral-bakterielle DNA in retinalen Pigmentepithelzellen Universität Leipzig, Dissertation 103 Seiten, 120 Literaturangaben, 19 Abbildungen, 10 Tabellen Die altersbedingte Makuladegeneration (AMD) zählt zu den häufigsten Erblindungsursachen in der westlichen Welt. Die Pathogenese der AMD ist mit lokaler und systemischer Entzün-dung assoziiert. Verschiedene Studien weisen darauf hin, dass virale und/oder bakterielle In-fektionen zu einer Verstärkung dieser Entzündungsreaktion in der alternden Retina führen. Um ein besseres Verständnis der bei der AMD ablaufenden pathologischen Mechanismen zu erlangen, wurden die Effekte des synthetischen viralen RNA Analogons Poly(I:C) und der viral-bakteriellen DNA (CpG-ODN) auf die Expression von Genen, die bei der Pathogenese der AMD involviert sind, verglichen. Die Untersuchungen wurden an kultivierten humanen retinalen Pigmentepithelzellen (RPE) durchgeführt. Es wurde gefunden, dass Poly(I:C) die Genexpression des Pattern-Recognition-Rezeptors (PRR) TLR3, der Transkriptionsfaktoren HIF-1α und p65/NF-κB, des angiogenen Faktors bFGF, von zahlreichen Entzündungsmediatoren (IL-1β, IL-6, TNFα, MCP-1, MIP-2) sowie der Komplementfaktoren C5, C9, CFB induziert. Weiterhin initiierte die Stimulation mit Po-ly(I:C) sowohl die Aktivierung der intrazellulären Signalproteine ERK1/2 und p38-MAPK als auch die Sekretion von bFGF und TNFα aus den Pigmentepithelzellen. Die Poly(I:C)-induzierte Gentranskription wird durch verschiedene Signalwege und Transkriptionsfaktoren vermittelt. CpG-ODN führte bei den RPE-Zellen nur zu einer geringen, transienten Erhöhung der Genexpression der Transkriptionsfaktoren p65/NF-κB und NFAT5 und der Komplement-faktoren C5 und C9. Die Wirkung viraler RNA und der moderate Einfluss viral-bakterieller DNA auf die Genex-pression bei RPE-Zellen legen nahe, dass vor allem virale RNA physiologische Veränderungen im RPE induziert und somit Entzündungsreaktionen in der alternden Retina verstärkt. Weiter-hin lässt sich schließen, dass eine selektive Inhibition einzelner Signalwege oder Transkripti-onsfaktoren im RPE wahrscheinlich nicht ausreicht, um die Entwicklung einer AMD effektiv zu verhindern.

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Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-02-06T15:57:09Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Tese_CaracterizacaoMolecularVirus.pdf: 4581267 bytes, checksum: ee0162884ca679c7419566551d00aa4a (MD5) / Approved for entry into archive by Ana Rosa Silva(arosa@ufpa.br) on 2014-02-10T12:08:40Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Tese_CaracterizacaoMolecularVirus.pdf: 4581267 bytes, checksum: ee0162884ca679c7419566551d00aa4a (MD5) / Made available in DSpace on 2014-02-10T12:08:40Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Tese_CaracterizacaoMolecularVirus.pdf: 4581267 bytes, checksum: ee0162884ca679c7419566551d00aa4a (MD5) Previous issue date: 2010 / FAPESPA - Fundação Amazônia de Amparo a Estudos e Pesquisas / Poucas informações estão disponíveis até o momento sobre os vírus do sorogrupo Gamboa (Bunyaviridae, Orthobunyavirus), desta forma, foi realizado, neste trabalho, estudo filogenético dos membros do sorogrupo Gamboa entre si e com outros orthobunyavírus ao nível gene Gn (M-RNA), além de infecção experimental em pintos recém nascidos da espécie Gallus gallus domesticus com a cepa Be AN 439546 do Vírus Gamboa (VGAM), e estudo sorológico em aves, outros animais silvestres e humanos de Tucuruí – Pará. A análise filogenética dos vírus do sorogrupo Gamboa demonstrou que esses vírus são geneticamente mais relacionados com membros do grupo Turlock e menos com os do grupo Simbu, e foram distribuídos em dois clados distintos (I e II), que estão de acordo com a atual classificação sorológica, de modo que o clado I inclui o complexo Gamboa e o clado II o complexo Alajuela. A cepa Be AN 439546 do VGAM apresentou tropismo pelo pulmão e fígado de pintos recém nascidos experimentalmente infectados, sendo a replicação viral nesses órgãos confirmada por imunohistoquímica, o que demonstra que o VGAM replica-se nessa ave. A detecção de anticorpos inibidores da hemaglutinação contra o VGAM e a confirmação por teste de neutralização em plasma de aves silvestres reforça a hipótese de que esses animais constituem o principal hospedeiro de amplificação no ciclo de manutenção do VGAM. Estudos moleculares do genoma completo dos vírus do sorogrupo Gamboa, assim como sobre a ecoepidemiologia do vetor e dos hospedeiros (principalmente aves), para o ciclo de replicação dos vírus, são importantes para confirmar as informações já existentes sobre esses vírus. / Presently, little information on Gamboa serogroup viruses (Bunyaviridae, Orthobunyavirus) is available. Thus, in this work, it was performed a comparative phylogenetic study on the members of the Gamboa serogroup and with other orthobunyaviruses to the level of the gene Gn (M-RNA); an experimental infections in the domestic bird (Gallus domesticus) using the strain Be AN 439546 of the Gamboa Virus (GAMV); and a serologic study using the Hemagglutination Inhibition (HI) test in serum samples of wild animals and humans collected in Tucuruí - Pará. The phylogenetic analysis of Gamboa group viruses demonstrated that they are genetically closely related to group Turlock viruses and less related to the Simbu group viruses. The group Gamboa viruses were distributed in two clades (I and II), that it is in agreement with the current serologic classification; the clade I correspond to the Gamboa complex and the clade II to the Alajuela complex. The strain Be AN 439546 presented tropism for chikens lung and liver, with viral replication in this organs confirmed by detection of viral antigens by immunohistochemistry. These results, demonstrate that this bird species is a susceptible host for GAMV replication. The detection of HI antibodies against GAMV, confirmed by neutralization tests were found in wild bird plasmas and reinforces the hypothesis that these animals constitute the main amplification hosts in the maintenance cycle of GAMV. Full length genome studies of the Gamboa serogroup viruses, as well as on the ecoepidemiology of their vectors and potential vertebrate hosts are needed to generate new data and to reinforce the understanding of the information already existent on those viruses.