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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Hur utvecklas den svenska minröjningsfunktionen inom marinen?

Arby, Nathaniel January 2009 (has links)
<p>Sjöminan har sänkt och skadat mer tonnage än alla andra vapensystem till sjöss. Då medel föder motmedel har sjöminan och minröjningen följt varandra i en lång duell.</p><p>Huvudsyftet med denna uppsats är att undersöka hur de svenska minröjningsförbanden utvecklas inom taktik och teknik och hur dessa komponenter förhåller sig till varandra. Uppsatsen söker även svaret på hur utvecklingen från minröjningsklass Landsort till minröjningsklass Koster skett.</p><p>Med hjälp av deskriptiv metod kommer <em>Militärstrategisk doktrin, Doktrin för marina operationer</em> samt <em>Försvarsmaktens läroböcker i Mineringstjänst</em>, <em>Minmotmedelstjänst</em> och <em>Minröjningstjänst</em> att användas för att redogöra hur den marina taktiken och tekniken utvecklas som ett medel i duellen mot sjöminan.</p><p>De svenska minröjningsfartygens taktiska och tekniska utveckling grundar sig på de militära basfunktionerna, <em>ledning, verkan, skydd, rörelse, underrättelse samt uthållighet</em>. Samtidigt utvecklas minröjningsförbanden i Försvarsmakten mot ett, både för personal och materiel, säkrare och effektivare förband.</p> / <p>The main purpose with this essay is to examine the development of the Swedish mine warfare branch both tactical and technical and how these two components are combined to maximize the effect. The essay also analyses the midlife upgrade of the MCMV Landsort class towards the MCMV Koster class.</p><p>This essay will describe on the basis of the Swedish doctrines and mine warfare textbooks how the naval tactics and technology function as a foundation for development of new means in the duel against the sea mine.</p><p>The sea mine is a weapon system that has been used during several centuries and has sunk more tonnage than all other weapon systems together. As long as there have been sea mines, there has also existed its counterpart, the mine counter measures.</p><p>The Swedish MCMV’s technological and tactical developments strive towards fulfilling the six mandatory functions in warfare, <em>command, effect, protection, mobility, intelligence and endurance</em>. The modern MCMV develops toward a more secure and efficient unit.</p>
12

Hur utvecklas den svenska minröjningsfunktionen inom marinen?

Arby, Nathaniel January 2009 (has links)
Sjöminan har sänkt och skadat mer tonnage än alla andra vapensystem till sjöss. Då medel föder motmedel har sjöminan och minröjningen följt varandra i en lång duell. Huvudsyftet med denna uppsats är att undersöka hur de svenska minröjningsförbanden utvecklas inom taktik och teknik och hur dessa komponenter förhåller sig till varandra. Uppsatsen söker även svaret på hur utvecklingen från minröjningsklass Landsort till minröjningsklass Koster skett. Med hjälp av deskriptiv metod kommer Militärstrategisk doktrin, Doktrin för marina operationer samt Försvarsmaktens läroböcker i Mineringstjänst, Minmotmedelstjänst och Minröjningstjänst att användas för att redogöra hur den marina taktiken och tekniken utvecklas som ett medel i duellen mot sjöminan. De svenska minröjningsfartygens taktiska och tekniska utveckling grundar sig på de militära basfunktionerna, ledning, verkan, skydd, rörelse, underrättelse samt uthållighet. Samtidigt utvecklas minröjningsförbanden i Försvarsmakten mot ett, både för personal och materiel, säkrare och effektivare förband. / The main purpose with this essay is to examine the development of the Swedish mine warfare branch both tactical and technical and how these two components are combined to maximize the effect. The essay also analyses the midlife upgrade of the MCMV Landsort class towards the MCMV Koster class. This essay will describe on the basis of the Swedish doctrines and mine warfare textbooks how the naval tactics and technology function as a foundation for development of new means in the duel against the sea mine. The sea mine is a weapon system that has been used during several centuries and has sunk more tonnage than all other weapon systems together. As long as there have been sea mines, there has also existed its counterpart, the mine counter measures. The Swedish MCMV’s technological and tactical developments strive towards fulfilling the six mandatory functions in warfare, command, effect, protection, mobility, intelligence and endurance. The modern MCMV develops toward a more secure and efficient unit.
13

A dimensão espacial do direito à cidade: acesso à equipamentos públicos e infraestrutura no Programa Minha Casa Minha Vida na Região Metropolitana de Salvador (2009 - 2015)

Tosta, Aline Oliveira 11 1900 (has links)
Submitted by Aline Tosta (aline_tosta@hotmail.com) on 2016-12-12T18:25:10Z No. of bitstreams: 1 DISSERTACAO_ALINE TOSTA.pdf: 14475747 bytes, checksum: 2d3ae32a6858e7797fa700a4d57848d1 (MD5) / Approved for entry into archive by Edilene Costa (ec@ufba.br) on 2016-12-21T21:15:57Z (GMT) No. of bitstreams: 1 DISSERTACAO_ALINE TOSTA.pdf: 14475747 bytes, checksum: 2d3ae32a6858e7797fa700a4d57848d1 (MD5) / Made available in DSpace on 2016-12-21T21:15:57Z (GMT). No. of bitstreams: 1 DISSERTACAO_ALINE TOSTA.pdf: 14475747 bytes, checksum: 2d3ae32a6858e7797fa700a4d57848d1 (MD5) / A história das cidades brasileiras é marcada por um intenso processo de urbanização impulsionado principalmente pelas atividades industriais. A precariedade do morar é uma das principais consequências desse processo. A política habitacional do país pode ser caracterizada pelos inúmeros programas habitacionais lançados, pela dificuldade de integração entre as políticas públicas e por ignorar a questão espacial no processo de gestão e planejamento das cidades. O resultado é a produção de moradias desconectadas da vida urbana, segregadas espacialmente e manutenção da negação do direito à cidade. O problema habitacional brasileiro e a negação do direito à cidade são temas amplos e complexos que refletem uma dimensão espacial que precisa ser aprofundada. Sendo assim, a presente pesquisa trás como contribuição para a discussão desse tema, a análise de um desses aspectos. Trata-se da atuação do Programa Minha Casa Minha Vida na Região Metropolitana de Salvador (2009 - 2015), com um enfoque na sua dimensão espacial e no atendimento do direito à cidade, utilizando como ferramenta de representação espacial o Sistema de Informações Geográficas - SIG. / The history of Brazilian cities is marked by an intense urbanization process mainly driven by industrial activities; and the precariousness of living is one of the main consequences of this process. The housing policy of the country can be characterized by the existence of many housing programs, by the difficulty of integration between public policies and by ignoring the spatial dilemma in the process of management and planning of cities. The result is a housing production detached from urban life, spatially segregated, keeping the denial of the right to the city. The housing problem in Brazil and the denial to the city are wide, complex themes which reflect a spatial dimension in need of a deeper thought. Thus, the purpose of this research is to bring an analysis of one of these aspects as a contribution to the topic. This research aims to study the performance of Programa Minha Casa, Minha Vida in the metropolitan area of Salvador de Bahia (2009-2015), with an emphasis on its spatial dimension and the fulfillment of right to the city, using GIS (Geographic Information System) as a tool for spatial representation.
14

Functional Analysis of the Murine Cytomegalovirus G Protein-coupled Receptor M33

Sherrill, Joseph D. January 2008 (has links)
No description available.
15

Prozessierung des pp89 MCMV MHC Klasse I Epitops durch das Proteasom

Voigt, Antje 20 April 2004 (has links)
Das Proteasom ist eine ATP- abhängige Protease, die sich aus vielen Untereinheiten zusammensetzt. Es ist für die Generierung der MHC Klasse I- restringierten Peptide verantwortlich, die im Folgenden auf der Zelloberfläche präsentiert werden. Nicht-funktionelle Proteine, die als so genannte defective ribosomal products (DRIP) bezeichnet werden, stellen eine wichtige Quelle für die Generierung von antigenen Peptiden, insbesondere jedoch von viralen Peptiden dar. Generell wird die Lehrmeinung vertreten, dass der Abbau von polyubiquitinierten Proteinen durch das 26S Proteasom zur Generierung von MHC Klasse I- Liganden führt. Allerdings ist weiterhin unklar, ob virale Proteine Ubiquitin- abhängig vom Proteasom abgebaut werden. Demnach sollte im Rahmen dieser Arbeit der Proteasom- abhängige Abbau des mCMV ie pp89 Proteins vor allem hinsichtlich einer Ubiquitinierung untersucht werden. Folglich wurden Konstrukte sowohl für ein rekombinantes pp89 (rek pp89) als auch für ein ODCpp89 Fusionsprotein entworfen. Somit konnten sowohl der in vitro Abbau dieser Proteine als auch die Prozessierung des spezifischen MHC Klasse I H2-Ld Epitops verfolgt werden. Experimente zum Nachweis von Ubiquitin- Protein- Konjugaten wurden in vivo mit stabil transfizierten Mausfibroblasten (B8 Zellen) durchgeführt. Die experimentellen Daten sprechen für einen schnellen in vitro Abbau des rek pp89 durch das 20S Proteasom. Das MHC Klasse I pp89 Epitop bzw. dessen 11mer Precursorpeptid wurden dabei mit hoher Präzision generiert. Spezifische CTL Assays weisen auf die Generierung des korrekten Epitops bzw. des Precursors hin. Nach Verdau des ODCpp89 Fusionsproteins durch 26S Proteasomen in Anwesenheit von Antizym konnten mit diesem Test ebenfalls das 9mer Epitop respektive das 11mer des pp89 nachgewiesen werden. Eine potentielle Ubiquitinierung des pp89 wurde in vivo in Zellkulturen untersucht. Nach Gabe von Proteasomeninhibitoren zu Mausfibroblasten konnte eine starke Akkumulierung von Ubiquitin- Konjugaten beobachtet werden. Allerdings konnte in den verschiedenen Versuchsansätzen kein Nachweis von pp89- Ubiquitin- Konjugaten erbracht werden. Demzufolge ist für die Generierung von viralen Epitopen ein Proteasom- abhängiger, aber Ubiquitin- unabhängiger Abbauweg denkbar. / The proteasome, an ATP-dependent, multisubunit protease, is responsible for the generation of most MHC class I restricted epitopes presented on the cell surface. Non-functional proteins, also known as defectice ribosomal products (DRiP), represent an important source for the generation of antigenic peptides in general and of viral epitopes in particular. It is widely accepted that the degradation of polyubiquitinated proteins by the 26S proteasome is a prerequisite for the generation of MHC class I ligands. However, the ubiquitin dependence for the proteasomal degradation of viral proteins is an issue so far unresolved. Therefore, the aim of this study was to analyze the proteasomal degradation of the mCMV ie pp89 in respect to an anticipated ubiquitinylation. Thus, a recombinant pp89 (recpp89) as well as an ODCpp89 fusion protein were generated. The in vitro processing of these proteins and the generation of a MHC class I H2-Ld epitope by proteasomes was further studied. Murine fibroblast cell lines (B8 cells) were used to analyze any in vivo evidence for potentially existing ubiquitin-protein conjugates. The experiments show that the recpp89 protein is rapidly degraded in vitro by the 20S proteasomes and that the correct MHC class I pp89 epitope or its 11mer precursor are generated with high fidelity. Furthermore, CTL assays, indicating the generation of the specific pp89 epitope or the 11mer precursor, also suggested a 26S proteasome-dependent degradation of the mCMV pp89-ODC fusion protein in the presence of antizyme. Treating cell cultures with proteasome inhibitors resulted in a significant accumulation of ubiquitin-conjugates in vivo. However, higher molecular weight pp89-ubiquitin conjugates were not detectable throughout the entire experimental set-up. Consequently, a proteasome-dependent, but ubiquitin-independent pathway can be postulated for the generation of viral epitopes.
16

Suppressor of Cytokine Signaling (SOCS)1 and SOCS3 Stimulation during Experimental Cytomegalovirus Retinitis: Virologic, Immunologic, or Pathologic Mechanisms

Alston, Christine I. 06 January 2017 (has links)
AIDS-related human cytomegalovirus (HCMV) retinitis remains the leading cause of blindness among untreated HIV/AIDS patients worldwide. Understanding the pathogenesis of this disease is essential for developing new, safe, and effective treatments for its prevention or management, yet much remains unknown about the virologic and immunologic mechanisms contributing to its pathology. To study such mechanisms, we use a well-established, reproducible, and clinically relevant animal model with retrovirus-induced murine acquired immunodeficiency syndrome (MAIDS) that mimics in mice the symptoms and progression of AIDS in humans. Over 8 to 12 weeks, MAIDS mice become susceptible to experimental murine cytomegalovirus (MCMV) retinitis. We have found in this model that MCMV infection significantly stimulates ocular suppressor of cytokine signaling (SOCS)1 and SOCS3, host proteins which dampen immune-related signaling by cytokines, including antiviral interferons. Herein we investigated virologic and/or immunologic mechanisms involved in this stimulation and how virally-modulated SOCS1 and/or SOCS3 proteins may contribute to MCMV infection or experimental MAIDS-related MCMV retinitis. Through pursuit of two specific aims, we tested the central hypothesis that MCMV stimulates and employs SOCS1 and/or SOCS3 to induce the onset and development of MCMV retinal disease. MCMV-related SOCS1 and SOCS3 stimulation in vivo occurred with intraocular infection, was dependent on method and stage of immune suppression and severity of ocular pathology, was associated with stimulation of SOCS-inducing cytokines, and SOCS1 and SOCS3 were differentially sensitive to antiviral treatment. In vitro studies further demonstrated that SOCS1 and SOCS3 stimulation during MCMV infection occurred with expected immediate early kinetics, required viral gene expression in cell-type-dependent and virus origin-dependent patterns of expression, and displayed differential sensitivity to antiviral treatment. These data suggest that SOCS1 and SOCS3 are stimulated by divergent virologic, immunologic, and/or pathologic mechanisms during MCMV infection, and that they contribute to the pathogenesis of retinal disease, revealing new insights into the pathophysiology of AIDS-related HCMV retinitis.
17

O valor do dinheiro no tempo: uma avaliação de empreendimentos do Programa Minha Casa Minha Vida - Faixa 1 / The time value of money: a valuation of enterprises of Program \"Minha Casa Minha Vida - Faixa 1

Guaritá, Gabriela Darini 18 June 2018 (has links)
Esta dissertação analisa a produção de moradias sociais direcionada às famílias de baixa renda no âmbito do Programa Minha Casa Minha Vida. Partindo dos principais índices econômico-financeiros utilizados em negócios imobiliários, a pesquisa revela as alterações do comportamento do mercado da construção civil do ramo habitacional na avaliação da rentabilidade do capital próprio enquanto aplicado nesse segmento. Baseada em estudos de caso, a pesquisa obteve acesso ao cronograma financeiro global das obras, bem como do Quadro de Composição de Investimento (QCI) e da Ficha de Resumo dos Empreendimentos (FRE), documentos obrigatórios na contratação das unidades junto à CEF. Somados às entrevistas com os agentes envolvidos, procurou-se elucidar as estratégias de expansão do capital imobiliário amparada pelo entendimento do desenvolvimento de uma viabilidade técnico financeira. Inicialmente, a proposta dessa pesquisa focava na análise do desempenho operacional e financeiro de dois empreendimentos construídos na cidade de Taboão da Serra, localizados lado a lado, e produzidos por duas modalidades do programa (Empresas x Entidades). No entanto, o empreendimento articulado pela entidade organizadora: o Movimento dos Trabalhadores Sem Teto (MTST), construído através de Empreitada Global, apresenta algumas similaridades com o empreendimento vizinho ao que se refere às estratégias de produção e de valorização do capital imobiliário. Diante disso, para complementar a análise da modalidade Entidades, a pesquisa avaliou os Condomínios Florestan Fernandes e José Maria Amaral, constituídos de fato por meio de autogestão direta. Nota-se com a aplicação desses métodos (fundamentados nos conceitos do valor do dinheiro no tempo), a reprodução de algumas práticas das grandes incorporadoras, inclusive na modalidade Entidades. Além disso, o desenho operacional do programa expõe os movimentos sociais às mudanças políticas econômicas e ao entendimento de técnicas financeiras complexas em função do longo prazo de maturação dos empreendimentos. / This dissertation analyzes the production of social housing directed to low-income families in the program \"Minha Casa, Minha Vida\". Based on the main economic-financial indexes used in real estate deals, the research reveals the changes in the behavior of civil construction housing market in the evaluation of the profitability of capital while applied in this segment. Based on case studies, the research obtained access to the overall financial schedule of the construction works, as well as the Investment Composition Framework (QCI) and the Summary of Enterprises Project (RES), mandatory documents for contracting the units with CEF. In addition to the interviews with the agents involved, it was sought to elucidate the mechanisms for the expansion of real estate capital, based on the understanding of the development of a technical financial viability. Initially, the proposal of this research was to compare the operational and financial performance of the two enterprises located in the city of Taboão da Serra, side by side, and produced from different modalities of the program (Companies vs. Entities). However, the enterprise articulated for the organizing entity: the \"Movimento dos Trabalhadores Sem Teto\" (MTST), built through the \"Empreitada Global\", presents some similarities with the neighboring building venture, as far as the strategies of production and valorization of the real estate capital are concerned. In view of this, to complement the analysis of the Entities modality, the survey evaluated the \"Florestan Fernandes\" and \"José Maria Amaral\" Condominiums, constituted in fact through direct self - management. Notice with the application of these methods (based on the concepts of the value of money in time), the reproduction of some practices of the great real estate developers, including the Entities modality. In addition, the operational design of the program exposes social movements to economic policy changes and the understanding of complex financial techniques as a function of the long-term maturity of ventures.
18

O valor do dinheiro no tempo: uma avaliação de empreendimentos do Programa Minha Casa Minha Vida - Faixa 1 / The time value of money: a valuation of enterprises of Program \"Minha Casa Minha Vida - Faixa 1

Gabriela Darini Guaritá 18 June 2018 (has links)
Esta dissertação analisa a produção de moradias sociais direcionada às famílias de baixa renda no âmbito do Programa Minha Casa Minha Vida. Partindo dos principais índices econômico-financeiros utilizados em negócios imobiliários, a pesquisa revela as alterações do comportamento do mercado da construção civil do ramo habitacional na avaliação da rentabilidade do capital próprio enquanto aplicado nesse segmento. Baseada em estudos de caso, a pesquisa obteve acesso ao cronograma financeiro global das obras, bem como do Quadro de Composição de Investimento (QCI) e da Ficha de Resumo dos Empreendimentos (FRE), documentos obrigatórios na contratação das unidades junto à CEF. Somados às entrevistas com os agentes envolvidos, procurou-se elucidar as estratégias de expansão do capital imobiliário amparada pelo entendimento do desenvolvimento de uma viabilidade técnico financeira. Inicialmente, a proposta dessa pesquisa focava na análise do desempenho operacional e financeiro de dois empreendimentos construídos na cidade de Taboão da Serra, localizados lado a lado, e produzidos por duas modalidades do programa (Empresas x Entidades). No entanto, o empreendimento articulado pela entidade organizadora: o Movimento dos Trabalhadores Sem Teto (MTST), construído através de Empreitada Global, apresenta algumas similaridades com o empreendimento vizinho ao que se refere às estratégias de produção e de valorização do capital imobiliário. Diante disso, para complementar a análise da modalidade Entidades, a pesquisa avaliou os Condomínios Florestan Fernandes e José Maria Amaral, constituídos de fato por meio de autogestão direta. Nota-se com a aplicação desses métodos (fundamentados nos conceitos do valor do dinheiro no tempo), a reprodução de algumas práticas das grandes incorporadoras, inclusive na modalidade Entidades. Além disso, o desenho operacional do programa expõe os movimentos sociais às mudanças políticas econômicas e ao entendimento de técnicas financeiras complexas em função do longo prazo de maturação dos empreendimentos. / This dissertation analyzes the production of social housing directed to low-income families in the program \"Minha Casa, Minha Vida\". Based on the main economic-financial indexes used in real estate deals, the research reveals the changes in the behavior of civil construction housing market in the evaluation of the profitability of capital while applied in this segment. Based on case studies, the research obtained access to the overall financial schedule of the construction works, as well as the Investment Composition Framework (QCI) and the Summary of Enterprises Project (RES), mandatory documents for contracting the units with CEF. In addition to the interviews with the agents involved, it was sought to elucidate the mechanisms for the expansion of real estate capital, based on the understanding of the development of a technical financial viability. Initially, the proposal of this research was to compare the operational and financial performance of the two enterprises located in the city of Taboão da Serra, side by side, and produced from different modalities of the program (Companies vs. Entities). However, the enterprise articulated for the organizing entity: the \"Movimento dos Trabalhadores Sem Teto\" (MTST), built through the \"Empreitada Global\", presents some similarities with the neighboring building venture, as far as the strategies of production and valorization of the real estate capital are concerned. In view of this, to complement the analysis of the Entities modality, the survey evaluated the \"Florestan Fernandes\" and \"José Maria Amaral\" Condominiums, constituted in fact through direct self - management. Notice with the application of these methods (based on the concepts of the value of money in time), the reproduction of some practices of the great real estate developers, including the Entities modality. In addition, the operational design of the program exposes social movements to economic policy changes and the understanding of complex financial techniques as a function of the long-term maturity of ventures.
19

Regulation des Zellzyklus durch das Maus- und Ratten-Zytomegalievirus

Neuwirth, Anke 29 November 2005 (has links)
Das humane Zytomegalievirus, ist ein ubiquitäres Pathogen, welches akute und persistierende Infektionen verursacht. Bei immunsupprimierten Patienten kann das Virus zu schweren Erkrankungen, wie Hepatitis, Pneumonie und bei kongenitaler Infektion außerdem zu Schädigungen des ZNS führen. HCMV blockiert die Zellproliferation durch einen Arrest am G1/S-Übergang des Zellzyklus, andererseits wird aber gleichzeitig die Expression S-Phase spezifischer Gene aktiviert. Teilweise lässt sich dies durch eine Virus vermittelte spezifische Inhibition der zellulären DNA-Repliaktion sowie durch eine massive Deregulation Zyklin-assozzierter Kinasen erklären. Zellkulturexperimente deuten darauf hin, dass die Zellzyklusalterationen wichtige Voraussetzungen für eine erfolgreiche Virusreplikation darstellen. Es ist hingegen nicht bekannt, welche Relevanz sie für die Virusvermehrung in vivo und das pathologische Erscheinungsbild im erkrankten Organismus besitzen. Diese Frage kann nur in einem Tiermodell sinnvoll angegangen werden. Aufgrund der Wirtsspezifität der Zytomegalieviren, ist man dabei auf die Verwendung der jeweiligen artspezifischen CMV angewiesen. Murines CMV (MCMV) und Ratten-CMV (RCMV) sind dabei die bislang bestuntersuchtesten Systeme. Das Anliegen dieser Arbeit war es zu prüfen, inwieweit die für HCMV beschriebenen Zellzyklusregulationen in MCMV und RCMV auf Zellkulturbasis konserviert sind. Es konnte gezeigt werden, dass sowohl RCMV als auch MCMV einen antiproliferativen Effekt auf infizierte Zellen besitzen und ebenso wie HCMV zu einem Zellzyklusarrest führen. Nager-Zytomegalieviren können Zellen auch in der G2-Phase arretieren und in dieser Zellzyklusphase auch effizient replizieren können. Die Infektion mit Nager-CMV führt außerdem auf breiter Basis zur Veränderung Zyklin-assoziierter Kinaseaktivitäten. Allen Zytomegalieviren ist die Hemmung der zellulären DNA-Synthese am G1/S-Übergang durch die Inhibition des replication licensing, dem Beginn der DNA-Synthese gemein. Durch diese vergleichende Studie wird einerseits deutlich, dass wesentliche funktionelle Schritte der Zellzyklusregulation zwischen den Zytomegalieviren konserviert sind, aber andererseits die zu Grunde liegenden molekularen Mechanismen zum Teil deutlich variieren. / Human Cytomegalovirus (HCMV) is an ubiquitous, species-specific beta-herpesvirus that, like other herpesviruses, can establish lifelong latency following primary infection. HCMV infection becomes virulent only in immunocompromised patients such as premature infants, transplant recipients and AIDS patients where the virus causes severe disease like hepatitis, pneumonitis and retinitis. Congenital infection produces birth defects, most commonly hearing loss. To develop rational-based strategies for prevention and treatment of HCMV infection, it is crucial to understand the interactions between the virus and its host cell that support the establishment and progression of the virus replicative cycle. In general, herpesviruses are known to replicate most efficiently in the absence of cellular DNA synthesis. What is more, they have evolved mechanisms to avoid the cell´s DNA replication phase by blocking cell cycle progression outside S phase. HCMV has been shown to specifically inhibit the onset of cellular DNA synthesis resulting in cells arrested with a G1 DNA content. Towards a better understanding of CMV-mediated cell cycle alterations in vivo, we tested murine and rat CMV (MCMV/RCMV), being common animal models for CMV infection, for their influence on the host cell cycle. It was found that both MCMV and RCMV exhibit a strong anti-proliferative capacity on immortalised and primary embryonic fibroblasts after lytic infection. This results from specific cell cycle blocks in G1 and G2 as demonstrated by flow cytometry analysis. The G1 arrest is at least in part caused by a specific inhibition of cellular DNA synthesis and involves both the formation and activation of the cells’ DNA replication machinery. Interestingly, and in contrast to HCMV, the replicative cycle of rodent CMVs started from G2 as efficiently as from G1. Whilst the cell cycle arrest is accompanied by a broad induction of cyclin-cdk2 and cyclin-cdk1 activity, cyclin D1-cdk4/6 activity is selectively suppressed in MCMV and RCMV infected cells. Thus, given that both rodent and human CMVs are anti-proliferative and arrest cell cycle progression we found a surprising divergence of some of the underlying mechanisms. Therefore, any question put forward to a rodent CMV model involving cell cycle regulation has to be well defined in order to extrapolate meaningful information for the human system.

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