Neurotrophic factor signaling modulates differentiation, axon growth and maintenance, synaptic plasticity and regeneration of neurons after injury. Ciliary neurotrophic factor (CNTF), a Schwann cell derived neurotrophic factor, has an exclusive role in axon maintenance, sprouting and synaptic preservation. CNTF, but not GDNF, has been shown to alleviate motoneuron degeneration in pmn mutant mice carrying a missense mutation in Tbce gene, a model for Amyotrophic Lateral Sclerosis (ALS). This current study elucidates the distinct signaling mechanism by which CNTF rescues the axonal degeneration in pmn mutant mice. ... / Neurotrophe Faktoren beeinflussendie die neuronale Differenzierung, das Wachstum und die Stabilisierung von Axonen sowie Synaptische Plastizität und die Regeneration von Neuronen nach Verletzung. Der von Schwannzellen synthetisierte neurotrophe Faktor Ciliary neurotrophic factor (CNTF) spielt eine wichtige Rolle bei der axonalen Erhaltung sowie bei der Induktion und Reduktion von axonalen Verzweigungen. Die Behandlung der pmn Mausmutante mit CNTF, aber nicht mit GDNF führt zu einem späteren Krankheitsbeginn und verminderten Fortschreiten der Motoneuronendegeneration. Diese Mausmutante, die eine Punktmutation im Tbce Gen trägt, dient als Modell für die Amyotrophe Lateralsklerose. Ziel der vorliegenden Arbeit war es, die zugrunde liegenden Signalkaskaden aufzudecken, die den CNTF-vermittelten Effekt auf den Krnakheitsverlauf bei der pmn Maus verursachen. ...

Identifying the molecular interactions of pathogens in different mosquito species is critical for understanding how mosquitoes transmit diseases. In this study, the role of the Jak-STAT immune signalling pathway in two different mosquito species, (Aedes aegypti L.) and (Culex quinquefasciatus L.) was assessed. Using in silico analysis tools, cell culture, and molecular techniques, changes in gene expression were assessed during lipopolysaccharide (LPS) challenge and West Nile virus (WNV) infection in the two species. It was found that activation of the Jak-STAT pathway occurred more quickly in Ae. aegypti cells compared to Cx. quinquefasciatus cells during LPS exposure. During WNV infections, no significant differences were observed, although preliminary evidence suggests that differential activation of the Jak-STAT pathway may exist between the two species. This research extends our understanding of the mosquito immune system while demonstrating the critical importance of vector-virus interactions across different mosquito species.

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Identifying the molecular interactions of pathogens in different mosquito species is critical for understanding how mosquitoes transmit diseases. In this study, the role of the Jak-STAT immune signalling pathway in two different mosquito species, (Aedes aegypti L.) and (Culex quinquefasciatus L.) was assessed. Using in silico analysis tools, cell culture, and molecular techniques, changes in gene expression were assessed during lipopolysaccharide (LPS) challenge and West Nile virus (WNV) infection in the two species. It was found that activation of the Jak-STAT pathway occurred more quickly in Ae. aegypti cells compared to Cx. quinquefasciatus cells during LPS exposure. During WNV infections, no significant differences were observed, although preliminary evidence suggests that differential activation of the Jak-STAT pathway may exist between the two species. This research extends our understanding of the mosquito immune system while demonstrating the critical importance of vector-virus interactions across different mosquito species.

The tradition of a strong church ruling in the Swedish society ages back to the very first start of Christianity reaching the country.  Due to the separation between the church and state in 2000 in Sweden, there have been a lot of changes. No longer would the church be able to influence the politics as it had been able to do before. Since Sweden is a democratic country, the decision had to be made in a voting amongst the parties. The purpose with this paper is to understand the argumentation made by the Swedish parties Socialdemokraterna, Kristdemokraterna and Centerpartiet. This has been made using a text analysis, which studies the argumentations made by the parties in their motions. The parties’ motions show whether they support the proposition of a separation between the church and state, or choose not to. The result shows that two of the parties, Socialdemokraterna and Kristdemokraterna, fully support the proposition. Centerpartiet argues that a separation amongst church and state would be devastating for both parts and therefore they choose not to recognize the proposition.  Furthermore the result shows that there has been a movement of secularization made in Sweden. This is shown in the argumentation made by the parties, who argue for a state built on politics free from religious influence.

The purpose of this study is to examine which security approach dominates Sweden’s strategy for combating human trafficking. The two approaches covered in this essay are the state- centred perspective, and the individual-centred perspective. These approaches are being used because those two approaches are on each end of the security spectrum, and it is important to discover from what approach Sweden is working. This is important because it might help us to get a bigger understanding on why certain policies are being made. It could also help us to understand the obstacles that might appear when actors work from different approaches, and the effects this might have for the people involved in human trafficking. This research paper attempts to answer the questions: From an analysis of Sweden’s work in combating human trafficking, is the state-centred or the individual- centred security perspective the most prominent? And Does the different actors covered in this study work from different security perspectives while combating human trafficking? The study is a qualitative study based on written materials and semi-structured interviews with human trafficking experts, police and policy makers. The conclusion of the study is that Sweden does not have a single approach in its security perspective towards human trafficking and that there is a slight difference among the actors from what perspective they are working to combat human trafficking. However, the research highlighted that the majority of the studied sources do state that the individual should be seen as the security focal-point in regards to human trafficking. The difference in how these two security perspectives are viewed leads to a discrepancy between the set security goal and the actual work carried out to combat human trafficking.

Made available in DSpace on 2015-07-22T20:49:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-26 / A via de sinalização Janus Kinase/Transdutores de Sinal e Ativadores de Transcrição (JAK/STAT) é uma das mais importantes vias de sinalização para transdução do sinal usadas pelas citocinas. Entretanto, o papel da via JAK/STAT na lesão de isquemia reperfusão (IR) hepática ainda não foi explorado. Este estudo foca no papel da proteína-quinase JAK2, que está acima de STAT-1 na cascata de sinalização JAK/STAT, e o seu papel no mecanismo da lesão de IR hepática. Isquemia quente parcial (lobos esquerdo e médio) foi induzida no fígado de camundongos C57BL/6 por 90 minutos, seguidos por 6 horas de reperfusão. Os animais foram tratados com o inibidor específico de JAK-2 (Tyrphostin AG490; 40 mg/kg, i.p) ou veículo (DMSO), 60 minutos antes do início da isquemia. O bloqueio de JAK2 resultou em significante redução da lesão hepática e da apoptose de hepatócitos. A análise imunohistoquímica revelou uma importante redução no infiltrado de macrófagos e de polimorfonucleares neutrófilos no tecido hepático dos animais que receberam AG490 anteriormente ao insulto isquêmico, comparado aos animais controle (DMSO). A expressão de citocinas pro-inflamatórias (TNF-α, IL-6, IL-1β) e das quimiocinas (CXCL-10 and CXCL-2) também estava reduzida no grupo tratado com AG490, comparado ao grupo controle. A análise da presença de células apoptóticas, através da técnica de TUNEL no tecido hepático dos camundongos, revelou menor número de hepatócitos em processo de apoptose no grupo tratado com AG490 consistente com o achado de western-blot que revelou menor expressão da proteína caspase-3 clivada em paralelo com o aumento da expressão da proteína anti-apoptótica Bcl-XL, no grupo que recebeu AG490. Para confirmar nossos achados in vivo nós testamos AG490 (75 mM) em culturas de macrófagos derivados da medula óssea (BMM) e em cultura de células da linhagem de hepatoma- CRL1830, ambas estimuladas com LPS (10 ng/ml). Em culturas de macrófagos derivados da medula óssea, AG490 reduziu a expressão gênica das citocinas e quimiocinas pró-inflamatórias (IL-6, IL-12p40, IL-1β, CXCL-10 e iNOS) que encontravam-se elevadas apos estimulação com LPS. Em cultura de células da linhagem de hepatoma- CRL1830, AG490 reduziu a expressão de caspase-3 clivada. Além do que, o bloqueio de JAK2 inibiu a fosforilação de STAT1 e STAT3. Pela primeira vez demonstramos que a sinalização por JAK2 é essencial na fisiopatologia da lesão de IR hepática, já que seu bloqueio seletivo protegue o fígado contra inflamação e apoptose. / The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling is one of the major pathways for cytokine signal transduction. However, the role of the JAK/STAT pathway in liver I/R is not clear. This study focuses on JAK2, which functions upstream of STAT-1 in JAK/STAT, and its role in the mechanism of liver IRI. Partial warm ischemia was produced in the hepatic lobes of C57BL/6 mice for 90min, followed by 6h of reperfusion. Mice were treated with JAK-2 inhibitor (Tyrphostin AG490; 40 mg/kg, i.p) or veicle, 60min prior to ischemic insult. JAK2 blockade resulted in significant reduction of hepatocyte apoptosis and liver injury. Macrophage and neutrophil infiltration, as assessed by immunohistochemistry, was markedly decreased in AG490-treated livers, compared with controls. The expression of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokines (CXCL-10 and CXCL-2) was also significantly reduced in AG490-treated group, compared with controls. AG490-treated livers showed less TUNEL positive cells and reduced cleaved caspase-3 protein expression in parallel with increased Bcl-XL expression. We employed AG490 (75 mM) in primary bone marrow-derived macrophage (BMM) and hepatoma cell (CRL1830) cultures, both stimulated with LPS (10 ng/ml). In BMM cultures, AG490 depressed otherwise LPSinduced pro-inflammatory gene expression programs (IL-6, IL-12b, IL-1β, CXCL-10 and iNOS). In hepatoma cells, AG490 reduced cleaved-caspase-3 expression. Moreover, JAK2 blockade inhibited STAT1 and STAT3 phosphorylation. This is the first report, which documents that JAK2 signaling is essential in the pathophysiology of liver IRI, as its selective blockage ameliorated the disease process and protected livers from inflammation and apoptosis. / TEDE / BV UNIFESP: Teses e dissertações / 103 p.

Tumour heterogeneity is a key hurdle for the effective treatment of cancer using oncolytic viruses (OVs). A better understanding of the pathways involved in delineating tumour cell resistance and hypersensitivity to OVs is critical in order to guide the development of new therapeutic strategies to enhance OVs. In this thesis, I performed a comparative genetic and epigenetic study of the murine OV-resistant colon cancer cell line CT26.WT and its hypersensitive subclone CT26.lacZ. This study led to the identification of retroviral insertion sites in AKAP7 and TP53RK genes, that are potentially involved in conveying sensitivity to infection by OVs and the dysregulation of the interferon antiviral response in the CT26.lacZ cell line. Gene overexpression and gene silencing experiments suggest a functional role of these proteins in controlling viral growth. Further investigation of these genes and their relationship to antiviral response pathways is warranted and may lead to novel strategies for improving the therapeutic activity of OVs.

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Uppsatsen avhandlar förekomsten av offentlig konst i tre olika områden i Uppsala med avsikt att undersöka skillnader mellan kommun (Svartbäcken), region (Akademiska sjukhuset) och stat (Kåbo). De olika instanserna undersöks i förhållande till det arbete som utförs med offentlig konst, hur de anpassar arbetet efter varandra och konstens placering. Denna information hämtas delvis från studier av instansernas tillgängliga dokument angående riktlinjer kring arbetet och från en fältstudie. Resultatet visade att både antal konstverk och konstens placering skiljer sig åt. Medan region och stat konstnärligt gestaltar platser där de verkar, negligerar kommunen i viss utsträckning områden där konst redan finns uppförd av annan aktör. Uppsatsens teoretiska utgångspunkter omfattar konstens positiva effekter på medborgare samt kritiska perspektiv som uppmanar till reflektion kring konsten, staden och hur invånare mottager verken. Analysen undersöker därmed offentlig konst i förhållande till de olika instanserna och diskuterar jämlik fördelning av konst samt vad detta kan innebära. Slutsatsen ställer flera nya frågor som kräver vidare undersökningar för att besvara men argumenterar att konsten ofta är riktad åt en eller flera målgrupper och att konsten i ett område inte fördelas med boendeantal i åtanke. Ytterligare observationer föreslår hur konsten bör placeras mer tillgängligt för alla.