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Dissertations / Theses on the topic 'STAT'
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Is'Harc, Hayaatun. "JAK/STAT signalling." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272414.
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Strickland, Janae. "The Role of STAT and the Jak/STAT Pathway In Mediating the Effects of Interleukin-6 on StAR Expression." Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1781.pdf.
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Une-Larsson, Martin. "Verkställighet mot främmande stat." Thesis, Stockholms universitet, Juridiska institutionen, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-129856.
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Lif, Zophie. "Stat i världen : En studie av Islamiska staten i förhållande till begreppet stat." Thesis, Mittuniversitetet, Avdelningen för samhällsvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-26888.
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Titel: Stat i världen – En studie av Islamiska staten i förhållande till begreppet stat Kurs: Statsvetenskap C, Mittuniversitetet, vårterminen 2015 Författare: Zophie Lif Nyckelord: Statsvetenskap, Islamiska staten, stat, begreppsdefinition, kvalitativ metod Bakgrund Islamiska staten är en av flera islamistiska rörelser som på senare tid vunnit stora politiska och territoriella framgångar. Organisationen utmärker sig genom att göra anspråk på ett världsomspännande kalifat som ska omfatta hela världens muslimska befolkning.I västvärlden har Islamiska staten främst uppmärksammat för sitt extrema våld, medan de i Mellanöstern av många grupper uppfattas som möjliga makthavare. Syfte Uppsatsens syfte är undersöka om och i vilken utsträckning Islamiska staten teoretiskt kan definieras som en stat. Undersökningen har gjorts med utgångspunkt i frågeställningen "Om och i vilken utsträckning kan Islamiska staten i teoretisk mening definieras som en stat?" Metod Undersökningen är en kvalitativ textanalys, där Islamiska staten prövas mot begreppet stat såsom det definieras av Max Weber. Det empiriska materialet analyseras utifrån en kategorisering av Webers teori. Resultatet har visat att Islamiska staten delvis, om än inte fullt ut, uppfyller Webers kriterier för en stat. Slutsats Studien visar att Islamiska staten, helt eller delvis, uppfyller vissa av de preciserade kriterier som definierar en stat. Utifrån studiens resultat dras slutsatsen att Islamiska staten av idag inte i tillräcklig utsträckning uppfyller villkoren för en stat, men samtidigt att det inte går att utesluta att organisationen en dag kommer att uppnå det målet.2015-06-03
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Lindström, Dag. "Skrå, stad och stat : Stockholm, Malmö och Bergen ca. 1350-1622 /." Stockholm : Almqvist och Wiksell, 1991. http://catalogue.bnf.fr/ark:/12148/cb35512925f.
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Laurén, Pär. "Sekt, stat och apokalyptiskt våld." Thesis, University of Gävle, Ämnesavdelningen för religionsvetenskap, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-3776.
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Denna uppsats behandlar det fenomen som uppstår när en, mer eller mindre isolerad, grupp religiöst hängivna människor, hamnar i en så pass allvarlig konflikt med staten och dess instutitioner att våldsamheter uppstår. Fenomenet brukar gå under beteckningen fanatiskt religiöst våld, och är i dess västerländska tappning mer eller mindre synonymt med sekter och sekterism.
P.g.a. ämnets digra karaktär är en kraftig begränsning nödvändig för att kunna behandla ämnet i en C-uppsats. Jag har därför gjort valet att koncentrera mig på de två mest extrema och medialt uppmärksammade fallen av religiöst sektvåld. Då ett av syftena med uppsatsen är att undersöka orsakerna till hur och varför väpnade konflikter uppstår mellan stat och sekt har jag valt att utesluta de fall där enbart kollektivt själmord av och med sektmedlemmarna utförts, utan inblandning av staten. Exempel på dylika är Heavens Gate (Hale-Bopp sekten) och allra senast den Ugandiska neo-katolska domedagssekten ”Restoration of the ten commandments of God”, där över tusen människor begick kollektivt självmord. Dessa och liknande händelser är onekligen mycket intressanta, men faller tyvärr utanför ramen för detta arbete.
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Hagberg, Axel. "Bankkrishantering : aktörer, marknad och stat." Doctoral thesis, Handelshögskolan i Stockholm, EHFF - Stiftelsen för Ekonomisk-historisk och Företagshistorisk Forskning, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:hhs:diva-1264.
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I likhet med i andra länder har det i Sverige under vissa högkonjunkturer uppstått ett så betydande kapitalöverskott, att den finansiella marknaden fått problem att bemästra flödena. Konsekvensen har blivit att den aggregerade risknivån ökat i takt med stigande tillgångspriser. När väl en kontraktion uppstått, har det saknats kapital för att i ordnade former bemästra de nya ekonomiska förutsättningarna. Det är den utvecklingen som föregått kriserna 1878/79, 1921/22 och 1991/92. Temporära insatser har då måst ske vid sidan av det befintliga institutionella systemet. Forskningen ger för Sveriges del en kriskronologi för det finansiella området med krisåren 1763, 1817/18, 1857/58, 1878/79, 1907/08, 1921/22, 1932/33 och 1991/92. Det har vid kriserna 1878/79, 1921/22 och 1991/92 förelegat ett betydande hot om kollaps av det finansiella systemet. Vid dessa tre tillfällen har det efter förhandlingar mellan bankerna och staten kommit att skapas temporära krishanteringsorganisationer – Järnvägshypoteksfonden 1879, AB Kreditkassan 1922 samt Securum AB 1992 – vid sidan om den svenska Riksbanken. Kriserna har hävts med hjälp av de temporärt skapade krisorganisationerna, vilka samtliga har haft en Lender of Last Resort-funktion. Krishanteringstekniken vid krisen 1921/22 kan ses som en vidareutveckling av den som kommit till användning 1878/79. Även om bakgrunden till krisen 1991/92 skiljer sig åt från de två här tidigare nämnda tillfällena, kom tekniken med överflyttandet av tyngande engagemang till ett nytt bolag att likna den teknik som användes redan av AB Kreditkassan. Trots detta betydde tidigare svenska erfarenheter mindre för krisen 1991/92 i detta fall. Idéerna till Securum hämtades istället från senare tids bankkrishantering i USA med inrättandet av så kallade ”bad banks”. Syftet med denna avhandling är att med en institutionell ansats klarlägga och analysera hur de två första av dessa tre finansiella kriser har hanterats. Avhandlingen belyser i detalj det förhandlingsdrama mellan statens och marknadens aktörer som föregått inrättandet av respektive krisorganisation.
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Hagberg, Axel. "Bankkrishantering : aktörer, marknad och stat /." Stockholm : Handelshögskolan i Stockholm : Ekonomiska forskningsinstitutet vid Handelshögskolan i Stockholm (EFI) [distributör], 2007. http://www2.hhs.se/EFI/summary/725.htm.
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Dawson, M. A. F. "JAK-STAT signalling at chromatin." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598423.
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The aim of my work was to explore the possibility that the mammalian JAK2 signalling pathway influences the structure and function of chromatin. I have demonstrated that JAK2 is present in the nucleus of both human haematopoietic cell lines and primary cells. My results suggest that JAK2 functions as a histone tyrosine kinase and phosphorylates histone H3 at tyrosine-41 (H3Y41). This novel histone modification, the first described tyrosine phosphorylation on any of the non-variant histones, regulates the binding of heterochromatin protein 1-alpha (HP1α) at a new binding site on chromatin. HP1α uses its chromo-shadow domain to bind the H3Y41 region. Phosphorylation of H3Y41 by JAK2 reduces its affinity for chromatin. This reciprocal relationship was given a functional context by demonstrating its relationship to the expression of a key haematopoietic oncogene Imo2. Genome-wide studies demonstrate that H3Y41ph is present at the 5’ end of genes and is highly correlated with active transcription. This is the first comprehensive genome wide mapping of a histone phosphorylation mark and potentially highlights a role for this novel modification in the regulation of transcription. H3Y41ph was also present at specific cis-regulatory elements on JAK2-STAT5 target genes and genome-wide mapping of STAT5 binding confirmed that STAT5 binding and H3Y41ph was coincident at a significant number of sites within the human genome. This interesting observation suggests that canonical JAK2-STAT5 signalling is not confined to the cytoplasma but also occurs at chromatin. These findings extend the existing paradigm of JAK-STAT signalling and provide a platform for a better understanding of this critical signalling pathway, which is important in both normal development and oncogenesis.
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Hjelmqvist, Ingvar. "Relationer mellan stat och kommun." [Stockholm] : Stockholms universitet, Statsvetenskapliga institutionen, 1994. http://books.google.com/books?id=yi0FAQAAIAAJ.
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Dawson, Charlotte Helen. "STAT 6 and IL-4 signalling." Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245716.
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Broughton, Nicola Ann. "Specificity in JAK/STAT signal transduction." Thesis, King's College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300540.
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Hedeager, Lotte. "Danmarks jernalder : mellem stamme og stat /." Aarhus : Aarhus Universitetsforlag, 1990. http://catalogue.bnf.fr/ark:/12148/cb35379836d.
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Zhu, Wei. "Negative regulation of JAK/STAT pathway /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3112843.
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Vogt, Katja L. "Endocytic regulation of JAK/STAT signalling." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/6655/.
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Leit?o, Lidiane Alves de Azeredo. "Influ?ncia das vias de sinaliza??o mTOR, STAT 3 e STAT 6 na gravidade da bronquiolite aguda." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2017. http://tede2.pucrs.br/tede2/handle/tede/7809.
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Introduction: acute bronchiolitis (AB) is an inflammatory disease of the airways considered the most common pathology of the lower respiratory tract in childhood. Responsible for a large number of hospitalizations in infants is one of the leading respiratory diseases worldwide, raising the costs of health care in infants. According to epidemiological data, between 75,000 and 125,000 children are hospitalized in the United States each year with infections caused by respiratory syncytial virus (RSV), accounting for approximately 25% of pediatric pneumonia and up to 70% of hospitalizations for acute bronchiolitis. Children with deficiencies in cell-mediated immunity can develop more severe and prolonged infections. Activation of the mTOR, STAT-3 and STAT-6 signaling pathways have been identified as key regulators in different functions of the immune system. The aim of this study was to investigate the relationship between the gene expression of mTOR, STAT-3, STAT-6 and AB severity. Methods: it is a cohort study that included a group of infants less than 12 months old with AB admitted to a tertiary hospital in Porto Alegre, Brazil. Nasopharyngeal lavage was collected from all patients and stored in Trizol solution at -80?C at the Biomedical Research Institute (IPB) of PUCRS for subsequent extraction of RNA and cDNA synthesis. Specific primers were used to verify the relative expression of mTOR, STAT-3 and STAT-6 by means of real-time PCR. The results obtained were correlated with AB severity markers such as hospitalization time and wheezing time. Results: for the analysis of expression of the mTOR signaling protein and transcription factors STAT-3 and STAT-6, 23 patients hospitalized with AB were included. A general correlation was made between clinical markers (days of hospitalization and days of wheezing) and expression of signaling pathways. Data were stratified according to severity markers and showed a trend towards decreased mTOR expression in patients with a wheezing time equal to or greater than 5 days (r = -0.702 and p = 0.024). However, the STAT-3 and STAT-6 signaling pathways were not correlated with AB severity factors when applied in this group of patients. Conclusion: transcription factors are essential for generating effective immune responses. mTOR, STAT-3 and STAT-6 participate in the expression of a variety of genes in response to cellular stimuli and may play a key role in the manifestation of the disease. Our data demonstrate the decrease in mTOR expression, with improvement in clinical markers of severity, but other studies are needed to reinforce this finding.
Introdu??o: a bronquiolite aguda (BA) ? uma doen?a inflamat?ria das vias a?reas considerada a patologia mais comum do trato respirat?rio inferior na inf?ncia. Respons?vel por um grande n?mero de hospitaliza??es em lactentes ? uma das principais doen?as respirat?rias em todo o mundo, elevando os custos de cuidados de sa?de em lactentes. Segundo dados epidemiol?gicos, entre 75.000 e 125.000 crian?as s?o hospitalizadas nos Estados Unidos anualmente com infec??es causadas pelo v?rus sincicial respirat?rio (VSR), respondendo por aproximadamente 25% das pneumonias pedi?tricas e at? 70% das interna??es por bronquiolite aguda (BA). As crian?as com defici?ncia na imunidade mediada por c?lulas podem desenvolver infec??es mais graves e prolongadas. A ativa??o das vias de sinaliza??o mTOR, STAT-3 e STAT-6 t?m sido identificadas como reguladores-chave em diferentes fun??es do sistema imune. O objetivo deste estudo foi investigar a rela??o entre a express?o g?nica de mTOR, STAT-3, STAT-6 e a gravidade da BA. M?todos: trata-se de um estudo de coorte onde foi inclu?do um grupo de lactentes de idade inferior a 12 meses, com BA, internados em um hospital terci?rio de Porto Alegre, Brasil. Foi coletado lavado nasofar?ngeo de todos os pacientes e armazenados em solu??o de Trizol ? temperatura de -80?C no Instituto de Pesquisas Biom?dicas (IPB) da PUCRS para posterior extra??o de RNA e s?ntese de cDNA. Foram utilizados os iniciadores espec?ficos para verificar a express?o relativa de mTOR, STAT-3 e STAT-6 por meio de PCR em tempo real. Os resultados obtidos foram correlacionados com marcadores de gravidade da BA como tempo de interna??o e tempo de sibil?ncia. Resultados: para a an?lise da express?o da prote?na de sinaliza??o mTOR e fatores de transcri??o STAT-3 e STAT-6, foram inclu?dos 23 pacientes hospitalizados com BA. Foi realizada uma correla??o geral entre os marcadores cl?nicos (dias de interna??o e dias de sibil?ncia) e a express?o das vias de sinaliza??o. Os dados foram estratificados de acordo com os marcadores de severidade e mostraram uma tend?ncia para a diminui??o da express?o de mTOR em pacientes com tempo de sibil?ncia igual ou superior a 5 dias (r = -0,702 e p = 0,024). No entanto, as vias de sinaliza??o STAT-3 e STAT-6 n?o foram correlacionadas com fatores de gravidade da BA quando aplicadas neste grupo de pacientes. Conclus?o: os fatores de transcri??o s?o essenciais para gerar respostas imunes eficazes. O mTOR, STAT-3 e STAT-6 participam na express?o de uma variedade de genes em resposta a est?mulos celulares e podem desempenhar um papel-chave na manifesta??o da doen?a. Nossos dados demonstram a diminui??o da express?o de mTOR, com melhora dos marcadores cl?nicos de gravidade, por?m outros estudos s?o necess?rios para refor?ar este achado.
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Moore, Rachel. "Regulation of JAK/STAT signalling by endocytosis." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22459/.
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The JAK/STAT pathway is a highly evolutionarily conserved signal transduction pathway, whose activation can lead to a broad range of cellular outcomes. The pathway is used repeatedly during multiple developmental stages and in adult tissue, and therefore tight regulation is required to enable accurate responses in a context specific manner. Internalisation and endocytic trafficking of signalling components provides a mechanism whereby spatial compartmentalisation can enable distinct signalling outputs. Within this study I have investigated the role of endocytosis in the regulation of the Drosophila melanogaster JAK/STAT pathway, and demonstrated that internalisation and endocytic trafficking differentially regulates target genes. Although the JAK/STAT pathway is transcriptionally competent and can regulate the expression of particular targets when the activated receptor is at the cell surface, receptor endocytosis and localisation to distinct endosomes is required for the expression of other targets. This appears to be context-dependent, as high levels of ligand stimulation overcomes endocytic regulation. STAT92E, the Drosophila JAK/STAT transcription factor, is a target of endocytic regulation. Although it is efficiently activated and undergoes nuclear translocation when endocytosis is perturbed, it is not capable of regulating a subset of target genes and therefore further STAT92E interacting partners and/or post translational modification must be required to fine-tune its transcriptional competency during endocytic trafficking. Utilising mass spectrometry I identified a novel STAT92E phosphorylation site, at threonine 702. Mutation of this threonine to prevent its phosphorylation, resulted in inhibition of STAT92E signalling and nuclear translocation, and also prevented phosphorylation of a highly conserved tyrosine residue at position 704, which is crucial for ligand activated JAK/STAT signalling outputs. Therefore, this study has enhanced our understanding of mechanisms that can modulate JAK/STAT activity. I have revealed an important role for endocytosis in fine- tuning Drosophila JAK/STAT signalling outputs and also identified a novel phosphorylation site which is crucial in the activity of STAT92E.
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Meissner, Torsten. "Structure-function analysis of the STAT1 N-domain." [S.l. : s.n.], 2005. http://www.diss.fu-berlin.de/2005/213/index.html.
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Begitt, Andreas. "Nukleocytoplasmatischer Transport und Geninduktion durch den Transkriptionsfaktor STAT1." [S.l. : s.n.], 2004. http://www.diss.fu-berlin.de/2004/177/index.html.
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Wernze, Stefanie [Verfasser], Jürgen K. [Gutachter] Mai, and Alfons [Gutachter] Hugger. "Quantifizierung von STAT 1 und STAT 2 in murinen Gehirnarealen unterschiedlicher Altersstufen / Stefanie Wernze ; Gutachter: Jürgen K. Mai, Alfons Hugger." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1113748052/34.
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Leal, Cervantes Ana Irene. "Transcriptional consequences of Jak-Stat signalling in haematopoiesis." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709253.
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Braim, Abdalla Hogir. "Allianspolitik i en stat med stat-till-nation obalans : ”Turkiets politik gentemot Kurdistanregionen i Irak och det kurdiska självstyret i Syrien”." Thesis, Försvarshögskolan, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:fhs:diva-5270.
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Alliansbildningsbeteende är ett viktigt och intressant ämne inom internationell politik och i internationella relationer. Enligt den traditionella maktbalansteorin allierar sig stater med andra stater för att balansera mot externa hot. I Steven R. Davids ”omnibalancing-teori” hävdas däremot att statsledare i tredjevärlden allierar sig med stater för att bekämpa interna hot. I föreliggande examensarbete, som är en fallstudie, är ambitionen att visa att turkiska republikens relation med Kurdistanregionen i Irak är ett fall av ”omnibalancering” såtillvida att Turkiet därigenom söker hålla den kurdiska rörelsen på hemmaplan i schack. Därför står Turkiet emot ett kurdiskt självstyre i Västra Kurdistan, syriska Kurdistan (Rojava), som har ideologiska kopplingar till den kurdiska rörelsen i turkiska Kurdistan (Norra Kurdistan). Med hänsyn till andra faktorer i relationer mellan stater (t ex i Turkiets relation till Södra Kurdistan) kan man uppmärksamma ekonomi- och energifrågorna. Vidare visar resultaten av fallstudier att etniska problem som ett internt hot påverkar statens utrikespolitik och alliansbeteende.
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Mütze, Jörg. "Immunhistochemische Analyse der Leptin-induzierten Transkriptionsfaktoren STAT3 und STAT5 im Gehirn der Ratte." Wettenberg : VVB Laufersweiler, 2005. http://deposit.d-nb.de/cgi-bin/dokserv?idn=977309983.
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Zanin, Natacha. "Role de STAM dans la régulation endosomale de la signalisation JAK/STAT induite par les IFNs." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS047.
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La première implication des récepteurs aux interférons de type 1 (IFNAR1) dans le contrôle de la voie Jak/STAT induite par les IFNs a été établie par mon laboratoire il y a une dizaine d'années (Marchetti et al., 2006). Une des questions fondamentales était alors de déterminer comment et pourquoi l'endocytose des IFNARs pouvait contrôler la voie Jak/STAT. Deux acteurs clés du tri endosomal ont attiré notre attention : Hrs (Hepatocyte growth factor-Regulated tyrosine kinase Substrate) et STAM (Signal Transducing Adaptor Molecule). Ces deux protéines constituent le complexe ESCRT-0 (Endosomal Sorting Complexes Required for Transport-0) les localisant, de manière idéale, à l'interface entre signalisation cellulaire et trafic membranaire.La combinaison de la biologie moléculaire et cellulaire, de la biochimie et de la microscopie à fluorescence, nous a permis d'établir que STAM s'associe au complexe IFNAR1 à la membrane plasmique afin d'y exercer son effet inhibiteur sur la signalisation Jak/STAT. Cette inhibition est levée lorsqu'IFNAR est libéré dans l'endosome et qu'il peut ainsi être recruté par Hrs sous la dépendance de l'IFN-α. En nous basant sur des expériences de déplétion par shRNA ou d'inhibition pharmacologique, nous avons identifié PTP1B (Protein Tyrosine Phosphatase 1B) en tant qu'activateur de la voie Jak/STAT induite par les IFNs. Le blocage sélectif de l'endocytose d'IFNAR par déplétion de clathrin, nous a permis de montrer que l'activation de PTP1B est inhibée à la membrane plasmique. Cela a été confirmé par des expériences d'interaction protéine-protéine (Proximity Ligation Assay) indiquant que STAM est constitutivement associé à IFNAR1, tandis que l'interaction entre IFNAR1 et Hrs a seulement lieu à l'endosome.Ainsi, nos résultats permettent d'établir un modèle dans lequel, à la membrane plasmique, STAM est un frein permanent à la signalisation Jak/STAT, qui est levé après l'endocytose d'IFNAR et sa libération dans l'endosome de tri. De plus, nous avons montré que l'interaction Hrs/STAM dans l'endosome précoce permet de différencier, de manière sélective, l'activation de la signalisation Jak/STAT médiée par l'IFN-α ou l'IFN-βA decade ago, my laboratory established the first role of type I IFNs receptor (IFNAR) endocytosis in the control of Jak/STAT signaling induced by type 1 IFNs (Marchetti et al., 2006). A salient question is now to elucidate why and how IFNAR endocytosis could control the Jak/STAT pathway. Two key players of endosomal sorting retained our interest: Hrs (Hepatocyte growth factor-Regulated tyrosine kinase Substrate) and STAM (Signal Transducing Adaptor Molecule). These two classical components of the ESCRT-0 (Endosomal Sorting Complexes Required for Transport-0) complex were ideally placed at the interface between signaling and membrane trafficking. By using a combination of molecular and cellular biology, biochemistry, and fluorescent microscopy, we could establish that STAM binds to the IFNAR complex at the plasma membrane to exert an inhibitory effect on Jak/STAT signaling. This inhibition is removed when IFNAR is delivered to the sorting endosome by interacting with Hrs upon IFN-α stimulation. Based on shRNA down-expression and pharmacological inhibition, we further involve the PTP1B (Protein Tyrosine Phosphatase 1B) as it activates Jak/STAT signaling upon IFN stimulation. We could also show that PTP1B activation is inhibited by STAM at the plasma membrane from experiments where IFNAR endocytosis was blocked by siRNA-mediated clathrin down-expression. This was further confirmed by protein-protein interaction experiments (Proximity Ligation Assay) showing that STAM was constitutively associated with IFNAR1, whereas the interaction between IFNAR1 and Hrs occured only at the sorting endosome. Our results therefore allow to draw a model where STAM is a constitutive handbrake on Jak/STAT signaling at the plasma membrane that is released after IFNAR endocytosis and delivery to the sorting endosome. We further show that Hrs/STAM interaction at the early endosome allows to selectively distinguish the activation of Jak/STAT signaling mediated by IFN-α or IFN-β
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Mello, Alexandra Siqueira. "Efeitos da desnutrição proteica na linfoproliferação e na produção in vitro de IFN-γ e IL-10 em células do baço. Quantificação de STAT-1 e STAT-3." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-02102013-152924/.
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A desnutrição modifica a resistência à infecção, alterando grande variedade de processos fisiológicos, incluindo a hematopoiese e a resposta imune. Os mecanismos exatos que comprometem o sistema imunológico em condições de desnutrição ainda não estão totalmente compreendidos, sendo que a desnutrição modifica a funcionalidade das células efetoras na resposta inflamatória/infecciosa, causando redução da síntese de citocinas pró-inflamatórias, além de alterações na hematopoiese. Os linfócitos têm papel-chave tanto na resposta imune inata quanto adaptativa. Nesse contexto, propusemo-nos a avaliar alguns aspectos da resposta linfoide esplênica em um modelo de desnutrição proteica. Camundongos BALB/c, machos, submetidos à desnutrição proteica, após perda de aproximadamene 20% do peso corpóreo, foram eutanasiados. Hemograma, mielograma, esplenograma e análise das concentrações séricas de proteína totais, albumina, pré-albumina e dosagem de imunoglobulinas G e M foram realizados. As células do timo e do baço foram coletadas e analisadas por citometria de fluxo - e foi realizado o ciclo celular. Para avaliação da linfoproliferação, as células esplênicas foram cultivadas, in vitro, e estimuladas com LPS ou ConA durante 72 horas. Foram quantificadas a capacidade de produção de INF-γ, IL-2 e IL-10 e a expressão de STAT- 1 e STAT-3. Os animais desnutridos apresentaram anemia, leucopenia e severa redução na celulariedade da medula óssea, com comprometimento no setor mieloide e diminuição da celulariedade do baço, com redução da população de linfócitos. Os animais desnutridos apresentaram alterações no desenvolvimento celular linfoide, alteração na capacidade de proliferação, menor produção de citocinas pró-inflamatórias, como IL-2, e, ao mesmo tempo, aumento da produção de IL-10. Os animais também apresentaram maior porcentagem de células CD3+ e CD4+ no baço em relação aos animais controle. Quando as células esplênicas foram estimuladas, apresentaram maior expressão de STAT-3 e menor expressão de STAT-1. Baseando-se nestes resultados, discutimos se deficiências nutricionais alteram a imunocompetência e aumentam o risco de infecções.Malnutrition modifies the resistance against infection by changing a variety of physiological processes, including the hematopoiesis and the immune response. The exact mechanisms that compromise the immune system in conditions of malnutrition is not yet thoroughly understood, since malnutrition modifies the functionality of the effector cells in inflammatory / infectious response, causing the reduction of the synthesis of proinflammatory cytokines, besides causing alterations in hematopoiesis. The lymphocytes have a key role in both innate and adaptive immune responses, in this context, we proposed to evaluate some aspects of lymphoid spleen cells response in a model of protein malnutrition. Male mice BALB / c submitted to protein malnutrition after approximately 20% loss of body weight were euthanized. The complete blood count, bone marrow examination, spleen cells count and analysis of serum total protein, albumin, pre-albumin and immunoglobulin G and M were performed. The thymus and spleen cells were collected and analyzed by flow cytometry as well as the cell cycle performed. For evaluation of the lymphocyte proliferation the spleen cells were cultivated in vitro and stimulated with LPS or ConA for 72 hours and the ability to produce IFN-γ, IL-2 and IL-10 as well as the expression of STAT-1 and STAT -3, were quantified. The malnourished animals presented anemia, leukopenia and severe reduction in celulariedade bone marrow with myeloid commitment in the sector and decreased celulariedade spleen, with reduced lymphocyte population. The malnourished animals showed changes in lymphoid cell development, abnormal proliferation capacity, reduced production of proinflammatory cytokines such as IL-2, and at the same time, increased production of IL-10. The animals also had higher percentages of CD3 + and CD4 + spleen compared to control animals. When spleen cells were stimulated, showed higher expression of STAT-3 and lower expression of STAT-1. Based on these results, we discussed whether nutritional deficiencies alter immunocompetence and increase the risk of infections.
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Stanton, John W. "DESIGN AND FABRICATION OF A MICROFLUIDIC ELECTROCHEMICAL PH-STAT." Cleveland, Ohio : Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1270498159.
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Thesis (Master of Sciences (Engineering))--Case Western Reserve University, 2010Department of EECS - Electrical Engineering Title from PDF (viewed on 2010-05-25) Includes abstract Includes bibliographical references and appendices Available online via the OhioLINK ETD Center
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Röder, Sabine. "Signaltransduktion durch JAK-STAT-Moleküle bei der Polyzythämia vera." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972175741.
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Moubarak, Patricia. "Expression und Regulation von JAK/STAT-Proteinen im Pankreas." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-53862.
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Widén, Pär. "Bedömningsmakten : Berättelser om stat, lärare och elev, 1960‐1995." Doctoral thesis, Linköpings universitet, Institutionen för beteendevetenskap och lärande, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-57852.
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Avhandlingen handlar om hur bedömningssystemet i bred bemärkelse presenterades i betygsdebatten i samband de politiska besluten om betygssystemet för gymnasiet mellan 1960 och 1995. Avhandlingen tar sin utgångspunkt i de berättelser som konstruerades under perioden. Syftet är att spåra och tolka förändringar i berättelserna om bedömning i anslutning till det politiska projektet att demokratisera och individualisera skolsystemet. Fokus är särskilt riktat mot de bedömningstekniker och innebörder för relationen mellan stat, lärare och elever som aktualiserades i samband med de två gymnasiereformerna. Härigenom synliggörs en viktig definitionskamp om statens förhållande till individen - lärare och elever - och hur makten i den nya enhetliga och demokratiska gymnasieskolan skulle förstås och organiseras. Avhandlingen pekar också på hur berättelser konkurrerar och hur en berättelse kan ges olika innebörder i förhållande till det politiska projektet att skapa en skola som tar till vara elevernas demokratiska möjligheter och lika villkor.This thesis explores how the system of examination, in broad terms, was presented in the debate about grading around the political decisions regarding the upper secondary school between 1960 and 1995. The point of departure is the narratives that were constructed during the time period. The main objective is to trace and interpret changes in the narratives of evaluation as a part of the political project of democratization and individualization of the school system. Special attention is given to the different grading techniques and implications for the relation between State, teacher and pupil that surfaced in and around the school reforms in 1964 and 1994. This also sheds significant light on the meaning constructions and struggle around the State’s relation to the individual - teachers and pupils - and how power was to be viewed and organized in the new homogenous and democratic school. The thesis also shows the rivalry of narratives and how a narrative can be given various meanings in relation to the political project of creating a school that advocates the democratic opportunities and equal rights of pupils.
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Omerovic, Ehlimana Manja. "Stat och pandemi : Tillit till institutioner under pandemisk krissituation." Thesis, Mittuniversitetet, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-13924.
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Reipschläger, Simone [Verfasser], and Klaus [Akademischer Betreuer] Aktories. "Untersuchung zur Aktivierung von STAT durch Cytotoxische-Nekrotisierende Faktoren." Freiburg : Universität, 2012. http://d-nb.info/1123473048/34.
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Pean, Claire. "JAK-STAT pathway in the control of mycobacterial infections." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/jakstat-pathway-in-the-control-of-mycobacterial-infections(cb788a0d-1c53-4f5c-8513-64c8cb50e08e).html.
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Though mammalian JAKs and STATs have been extensively studied over the past 20 years, many aspects of their in vivo function remain unclear. In particular, their roles in control of infection with pathogens remain murky and confusing. One difficulty in understanding how these pathways regulate inflammation is the presence of complex compensatory mechanisms between the different JAK and STAT proteins. In the Dionne lab, we use the fruit-fly Drosophila melanogaster as a model to study the in vivo functions of the JAK/STAT pathway in mycobacterial infection. Flies contain only one JAK (hop), one STAT (STAT92E), and three identified interleukin-like signals to activate signalling (upd, upd2, upd3). I show that, in Drosophila, the STAT-activating cytokine Upd3 is harmful to the host upon mycobacterial infection. Flies lacking upd3, or in which the JAk/STAT pathway is inhibited in phagocytes, show improved survival, decreased mycobacterial numbers, and delayed immune cell death. Strikingly, I find that JAK/STAT signalling acts in concert with other inflammatory signals to regulate expression of Atg2 in Drosophila phagocytes. In isolation or upon infection, STAT activation inhibits Atg2 expression and the ability of other, unknown signals to promote Atg2 expression. Increased Atg2 expression, as is seen in infected animals lacking either the cytokine Upd3 or STAT92E, promotes killing of intracellular bacteria and accumulation of large lipid droplets of unusual shape. I suggest an autophagy-independent mechanism by which Atg2 could reduce bacterial growth, involving the control of lipid body morphology. In this thesis, I show a mechanism by which JAK/STAT controls bacterial growth through inhibition of autophagy gene expression and demonstrate that this inhibition is detrimental to the survival of the host. In addition, I demonstrate that upd3 signalling is also required for glucose homeostasis suggesting a role for Upd3 in regulating gluconeogenesis and glycolysis.
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Wiklund, Roine. "Riksgränsbanans elektrifiering : Stat och företag i samverkan: 1910-1917." Doctoral thesis, Luleå tekniska universitet, Samhällsvetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-17409.
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Syftet med föreliggande doktorsavhandling i teknikhistoria är att öka kunskapen om varför, men framförallt hur och under vilka villkor den första elektrifieringen av en statsägd järnväg genomfördes i Sverige. Arbetet med Riksgränsbanans elektrifiering pågick 1908-1917 och var på många sätt ett unikt pionjärprojekt. Två stora tekniska system skulle där komma att sammankopplas med varandra; artonhundratalets mogna järnvägssystem med nittonhundratalets nya elkraftsystem. Riksgränsbanan, den omkring 130 km långa nordligaste delen av Malmbanan mellan Kiruna och Riksgränsen, var världens dittills nordligaste järnväg att elektrifieras och det subarktiska klimatet ställde stora krav på utförandet av tekniska komponenter. Den geografiska lokaliseringen innebar dessutom att de långa avstånden till beslutsfattare inom statsförvaltning och företag måste hanteras. Därutöver genomfördes projektet i en tidsperiod präglad av protektionism, nationalism och internationella konflikter, yttre faktorer som alla också påverkade projektets utformning och genomförande. Att det var Riksgränsbanan som blev den första statliga järnvägslinje att elektrifieras i Sverige berodde på att staten 1907 gått in som hälftenägare i gruvbolaget LKAB och att nya avtal fastställde en ökad brytning och transport av järnmalm, från 1,5 miljoner ton årligen 1908 till 3,85 miljoner ton 1918. Denna mängd kunde inte transporteras inom befintligt system med ångdrift utan omfattande investeringar, vilket innebar att en systemomvandling till elektrisk drift ansågs vara ett bättre alternativ. I maj 1910 beslutade riksdagen anslå 21,5 miljoner kr till projektet som skulle drivas av Järnvägsstyrelsens byrå för elektrisk drift i samverkan med företagen Siemens och ASEA. Kontraktsskrivningen ställde hårda krav på företagen gällande prestanda och utförande och Järnvägsstyrelsen kunde när som helst, senast två år efter övertagandet av driften av banan, besluta att upphäva kontraktet och kräva att företagen återställde anläggningen till ursprungligt skick.Det var en mängd tekniska subsystem och komponenter som skulle färdigställas och sättas samman för att det tekniska primärsystemet ”den elektrifierade Riksgränsbanan” skulle fungera. Speciellt färdigställandet av loken och isolatorerna till ledningssystemet omgärdades av problem som kom att försena projektets färdigställande. Problemen var både organisatoriska och tekniska till sin natur men kunde efterhand åtgärdas genom att det utarbetades bättre rutiner vid korrespondens och annan kontakt mellan aktörerna samt genom att det togs större hänsyn till lokala klimatologiska förhållanden i samband med teknikutveckling. I sin roll som byrådirektör för byrån för elektrisk drift skulle Ivan Öfverholm visa sig vara en stark representant för beställaren och han spelade en central roll för projektets genomförande. Öfverholm kan i detta sammanhang kategoriseras som en offentlig systembyggare som med fast hand styrde projektet. Ibland innebar detta att Öfverholm hamnade i direkt konflikt med företagens representanter men ofta fungerade han också som medlare i de konflikter som ideligen uppstod mellan Byråns och företagens lokala representanter vid anläggningen. Den tvååriga garantitiden inleddes den 1 oktober 1915 och i slutet av 1917 hade nästan samtliga kvarstående arbeten vid anläggningen fullföljts och SJ kunde ta över anläggningen. Slutomdömet om Riksgränsbanans elektrifiering var överlag positivt och 1919 beslutade riksdagen att elektrifiera resterande del av Malmbanan, vilket var genomfört från Narvik till Luleå sommaren 1923. Det banbrytande arbetet i den norrländska ödemarken med att elektrifiera Sveriges nordligaste järnväg var därmed avslutat.Godkänd; 2012; 20120221 (roiwik); DISPUTATION Ämnesområde: Teknikhistoria/History of Technology Opponent: Dr Mats Fridlund, Institutionen för filosofi, lingvistik och vetenskapsteori, Göteborgs universitet Ordförande: Biträdande professor Kristina Söderholm, Institutionen för ekonomi, teknik och samhälle, Luleå tekniska universitet Tid: Fredag den 20 april 2012, kl 10.15 Plats: A1547, Luleå tekniska universitet
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Devergne, Olivier. "Étude de la voie JAK/STAT chez Drosophila melanogaster." Nice, 2006. http://www.theses.fr/2006NICE4030.
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Chez les mammifères, la voie de signalisation JAK/STAT est activée en réponse aux cytokines et aux facteurs de croissance. Son activation stimule la prolifération, la différentiation, la migration cellulaire ainsi que l'apoptose. Nous montrons que la voie JAK/STAT et son récepteur Domeless (Dome), un récepteur de la famille des récepteurs aux IL-6, sont requis pour la différenciation et la migration des cellules de la bordure, un modèle d'invasion cellulaire qui se déroule au cours de l'ovogenèse chez la drosophile. Nous nous sommes ensuite intéressés aux mécanismes impliqués dans le contrôle de la voie de signalisation JAK/STAT. En effet, la voie de signalisation commence à être bien connue, en revanche le rôle de l'endocytose des récepteurs aux cytokines sur la transduction du signal est peu caractérisé. Grace à des analyses génétiques in vivo et des expériences en culture cellulaire, nous montrons que la fixation du ligand induit l'endocytose clathrine dépendante du complexe récepteur/ligand. Après internalisation, ces complexes traversent les différents compartiments endosomaux et sont dirigés vers le lysosome afin d'y être dégradés. Cette dégradation permet la désensibilisation de la voie JAK/STAT. De façon intéressante, le blocage de l'endocytose de Dome, grace à un mutant de la clathrine, entraine la diminution de l'activité de la voie JAK/STAT, suggérant que le recrutement de la clathrine et la formation des vésicules de bourgeonnement sont requis pour l'activation de la voie. La fixation du ligand n'est pas suffisante. De plus, le blocage du trafic au niveau de différents compartiments endosomaux, en utilisant des mutants rab5, hrs ou dor entraine également une inhibition de la voie JAK/STAT indiquant que l'endocytose et le trafic intracellulaire sont nécessaires pour la transduction du signal. Nos résultats révèlent ainsi un rôle essentiel de l'endocytose dépendante de la clathrine pour la transduction du signal in vivoIn mammals, the JAK/STAT signaling pathway is activated in response to cytokines and growth factors to control blood cell development, proliferation and cell determination. We show that the JAK/STAT pathway and its receptor Domeless (Dome), a receptor of the IL-6 receptor family, are required for the differentiation and the migration of border cells during drosophila oogenesis which represent a powerful model to study cell invasion. We then became interested into the role of endocytosis as a mechanism to control JAK/STAT signaling. Indeed, the transduction machinery in several models is well known, however the function of cytokine receptor endocytosis on signaling remains poorly characterized. Using both in vivo genetic analysis and cell culture assays, we show that ligand-binding induces clathrin-dependent endocytosis of receptor-ligand complexes which traffic through the endosomal compartment and are targeted to the lysosome for degradation, leading to the desensitization of JAK/STAT activity. Surprisingly, blocking endocytosis of Dome using clathrin mutants led to a downregulation of JAK/STAT signalling, suggesting that clathrin recruitment and formation of budding vesicles are required for JAK/STAT signaling and that ligand binding is not sufficient to activate the pathway. In addition, disrupting endocytosis of Dome in distinct endosomal compartments, using rab5, hrs, or dor mutants, also led to a reduction of signaling indicating that endocytosis and intracellular trafficking are necessary for signaling. Altogether, our data reveal an essential role of clathrin dependent endocytosis for JAK/STAT signalling in vivo
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Talerico, Cassandra. "Temporal Activation of the JAK-STAT Pathway in Relation to Cardiac Gene Expression in a Mouse Model of Cardiac Dysfunction." Cleveland State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=csu1197055735.
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Pudic, Samanta. "Relationen mellan stat och kommun när en flyktingförläggning skall lokaliseras." Thesis, Karlstad University, Karlstad University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-1708.
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Abstract
Essay in political science, C-level, by Samanta Pudic´, spring semester 2008. Tutor: Susan Marton. “The relationship between national government and local municipality when a refugee centre shall be located.”
The purpose of this essay is to examine the relationship between government and municipality with the help from the interdependens theory when a refugee centre is located. To be able to say something about the relationship between those two actors I have been using two municipalities as examples. I have interviewed two politicians who work in two municipalities and two head employees who work at the Swedish Migration Board. I have, on the basis of the interdependency theories four identified factors which affect the relationship between the government and the municipalities and I have designed seven assumptions which shall help me implement the interviews, the analysis and the conclusion.
The examination is thereby a case study, so that I can examine the relationship deeper between national government and local municipality with help from my two examples and the elite interviews. My purpose is not to generalise my conclusions for the whole of Sweden, but rather from the historical examples, examine how a relationship between government and municipalities can look like when a refugee centre shall be located.
The answer to my research question is that the relationship between the government and the two municipalities are symmetrical with low dignity. By this it means that both the state and the municipalities are mutual dependent on each other and it isn’t so difficult for them to have a mutually beneficial relationship.
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Andersson, Lars. "Från stat till koloni : En historia om tvångsarbete i Kongo." Thesis, Uppsala University, Department of Economic History, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8357.
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Sundström, Göran. "Stat på villovägar : Resultatstyrningens framväxt i ett historisk-institutionellt perspektiv." Doctoral thesis, Stockholms universitet, Statsvetenskapliga institutionen, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7101.
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I avhandlingen diskuteras framväxten av den rationalistiska styrmodell - resultatstyrning - som i dag är tänkt att tillämpas i staten. Dels diskuteras denna politiska institutions historiska närvaro i staten. Den spåras tillbaka till den programbudgeteringen. Institutionen har visserligen förändrats under de nära fyrtio år som förflutit sedan programbudgeteringen introducerades i staten. Förändringarna har dock främst gällt tillämpningen av olika metoder och tekniker. Vad gäller tillkomsten av nya metoder och tekniker har stabiliteten varit betydligt större. Och beträffande de mer grundläggande idé- och tankemönster som konstituerar institutionen, och tillika dess grundläggande målsättningar, påvisar undersökningen mycket stor stabilitet. I avhandlingen görs också ett försök att förklara styrmodellens beständighet. Frågan aktualiseras av att lärandeprocessen har haltat i flera avseenden. Erfarenheter som vunnits i tidigare skeden av processen inte har utnyttjats i senare skeden, konkreta problem som iakttagits i utvärderingar har bara i begränsad utsträckning diskuterats och relaterats till föreslagna lösningar och resultat från försöksverksamheter har ofta inte inväntats. Kritiska diskussioner som pågått i de ansvariga aktörernas omvärld har också haft svårt att få genomslag. Händelseutvecklingen förklaras utifrån ett historisk-institutionellt perspektiv och olika teorier om byråkratins makt. Det görs gällande att olika initiala beslut som fattades kring 1960 skapade olika självförstärkande krafter, som kom att verka stabiliserande på den studerade institutionen. Tre sådana krafter diskuteras: För det första hävdas att besluten gav ansvariga organisationer, och personer inom dessa organisationer, incitament och möjligheter att vidmakthålla institutionen; det har legat i deras (egen)intresse att bevara och utveckla den. Genom att de tidigt fick starka positioner har de också kunnat verka för detta. Genom att organisera verksamhet och personer och genom att kontrollera information har aktörerna sett till att behålla kontrollen över institutionen. För det andra hävdas att utvecklingsarbetet under långa perioder, och som en följd av olika initiala beslut, har letts av små och sluta grupperingar bestående av personer från ett fåtal organisationer (främst budgetavdelningen, RRV och Statskontoret). Tendenser till grupptänkande har uppstått. Genom att främst diskutera internt sinsemellan, och genom att skärma av källor som hade kunnat ge information om alternativa perspektiv och handlingsalternativ, har personerna inom dessa grupperingar blivit alltmer övertygade om det riktiga i att bygga vidare på den studerade institutionen. För det tredje hävdas att en särskild profession i ett tidigt skede av processen, och som en följd av olika initiala beslut, tog ett fast grepp om händelseutvecklingen. Institutionen kom från början att kläs i en ekonomiteoretisk språkdräkt, som gjorde att en viss typ av experter blev särskilt efterfrågade inom ansvariga organisationer, och även i statsförvaltningen i övrigt. Ekonomiadministrationen kom på detta sätt successivt att byggas ut, med följden att det ekonomiadministrativa språkbruket fick ett än fastare och än vidare fotfäste i statförvaltningen, vilket i sin tur ytterligare stärkte ekonomiprofessionens grepp om utvecklingen. Dominansen av en särskild profession har försvårat nytänkande och medfört att samma lösningar tenderat att återkomma.The book discusses the origin and development of management by results in Swedish state administration. The historical presence and stability of this political institution is analysed. It is argued that it can be traced to program budgeting, which was introduced in the early 60s, and that the institution has been marked by a high degree of stability. An attempt is made to explain the constancy of the steering model. The question is brought to the fore by the fact that the learning process has failed in several respects. The course of events is explained from a historical-institutional perspective and different theories of bureaucratic power. It is asserted that different initial decisions made in connection to the introduction of PB created different positive feedbacks, which were to have stabilizing effects on the institution.
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Mattsson, Susanna. "Från stat till marknad : effekter på nätverksrelationer vid en bolagiseringsreform /." Stockholm, 1998. http://www.hhs.se/efi/summary/486.htm.
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Chen, Qian. "THE INTERACTIONS BETWEEN JAK/STAT SIGNALING LIGANDS IN DROSOPHILA MELANOGASTER." UKnowledge, 2014. http://uknowledge.uky.edu/biology_etds/23.
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The development of multi-cellular organisms requires extensive cell-cell communication to coordinate cell functions. However, only a handful of signaling pathways have emerged to mediate all the intercellular communications; therefore, each of them is under an array of regulations to achieve signaling specificity and diversity. One such signaling pathway is the Janus Kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) pathway, which is the primary signaling cascade responding to a variety of cytokines and growth factors in mammals and involved in many developmental processes. This signaling pathway is highly conserved between mammals and Drosophila, but the Drosophila JAK/STAT pathway possesses only three ligands: Unpaired (Upd), Upd2 and Upd3. Co-localized expression patterns of the ligands at several developmental stages raise the possibility that they physically interact. This work was aimed at testing the protein-protein interactions between Upd-family ligands and exploring possible outcomes of ligand oligomerization.
Physical interactions between Upd-family ligands were tested using a Bimolecular Fluorescence Complementation (BiFC) assay. The data suggested that homotypic interactions of Upd2 and Upd3 were stronger than their respective heterotypic interactions with Upd, and the homotypic interaction between Upd molecules was the weakest. In addition, the homotypic interaction of Upd3 was confirmed using yeast two-hybrid interaction assays. To identify protein domains critical for Upd3/Upd3 interaction, a series of poly-alanine substitutions were made to target the 6 conserved domains of Upd3. All 6 substitutions altered the strength of Upd3/Upd3 interaction and drastically reduced Upd3-induced JAK signaling activity. In addition, poly-alanine substitutions of some domains also affected Upd3 extracellular localization or protein accumulation.
Potential outcomes of interactions between Upd-family ligands were tested both in vitro and in vivo. The interaction between Upd and Upd3 did not significantly change the level of JAK signaling activity. However, loss of Upd3 restricted the distribution of Upd in egg chambers and consequently altered the follicle cell composition. Therefore, Upd/Upd3 interaction is likely to affect the range rather than the intensity of JAK signaling in egg chambers. In summary, this study suggested the possibility of ligand oligomerization as a mechanism for regulating signaling pathways in order to achieve signaling specificity and diversity during development.
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Han, Ho-chun, and 韓浩俊. "JAK-STAT pathway as potential target of acute myeloid leukemia." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B50534208.
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Acute myeloid leukemia (AML) is a group of heterogeneous diseases characterized by an abnormal increase in myeloblasts. Despite intensive chemotherapy and allogeneic bone marrow transplantation, the treatment outcome of AML remains unsatisfactory, with a cure rate of only about 30%. Therefore, novel therapeutic strategies targeting the pathogenetic pathways of leukemia initiation and progression are needed. Using intracellular phospho-flow analysis with normal bone marrow as reference, we detected an increase in phosphorylated-STAT5 (pSTAT5) in three leukemic cell lines (K562, KG-1 and ML-2) and 15 primary AML samples. Treatment with specific JAK2 inhibitor TG101209 and JAK2/3 inhibitor AG490 significantly reduced pSTAT5 level and leukemia cell growth associated with an increase in apoptosis and decrease in cellular proliferation. The clonogenic activities of these leukemia cell lines were also significantly reduced. Furthermore, treatment with these inhibitors in K562 and KG-1 also significantly reduced the WNT signaling activity, as enumerated by the TOP/FLASH luciferase assay. In addition, genes associated with oncogenic potential and anti-apoptosis were significantly reduced, consistent with the pathogenetic role of JAK-STAT pathway.
In summary, the present study highlighted the importance of the JAK2-STAT5 signaling pathway in sustaining AML. The results may open up a new avenue whereby new therapeutic strategies targeting AML can be designed.published_or_final_version
Medicine
Master
Master of Philosophy
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Stec, Wojciech. "Molecular analysis of the Drosophila JAK/STAT pathway receptor complex." Thesis, University of Sheffield, 2013. http://etheses.whiterose.ac.uk/4509/.
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The JAK/STAT signalling pathway plays a central role in numerous biological processes contributing to development and maintenance of homeostasis. Drosophila melanogaster offers a conserved JAK/STAT pathway with much lower redundancy. For this reason, the fruit fly was used as a model organism to investigate genetic interactions and functions of the JAK/STAT pathway in the context of the whole organism. However, very little is known regarding the molecular mechanisms governing the Drosophila JAK/STAT pathway. Here, we present a molecular analysis of the sole receptor of the JAK/STAT pathway in Drosophila, Dome. We show that Dome shares characteristics with different sub-families of mammalian cytokine receptors. Specifically, the identified JAK binding site in Dome is reminiscent of that found in IFN? receptor, while constitutive endocytosis leading to lysosomal degradation shares similarities with the Leptin receptor. An increase in tyrosine phosphorylation and a shift in the ubiquitination pattern of the receptor in response to ligand binding are also described. Furthermore, the structure-function analysis of socs36E, the only SOCS-like protein in the Drosophila genome that can potently suppress the JAK/STAT pathway, revealed two independent mechanisms of action. Firstly, SOCS36E affects stability of the receptor, most likely by forming ubiquitin ligase via the SOCS box domian, a mechanism well described for all mammalian SOCS proteins. Secondly, regulation of Dome phosphorylation by the N-terminal domain of SOCS36E contributes to suppression of the JAK/STAT pathway in a SOCS box independent manner. Finally, two alleles of the Drosophila JAK that give rise to a phenotype reminiscent of human leukaemia, hopTuml and hopT42, are shown to increase transcriptional activity of the pathway reporter without increasing phosphorylation of STAT. Both mutations cause constitutive activation of the kinase independently of the receptor. Moreover, autophosphorylation kinetics of both mutants are unaltered, compared to the wild-type Hop, suggesting non-canonical signalling to be the underlying cause of oncogenicity.
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Thomas, Sally J. "Genetic and chemical modulators of JAK/STAT signalling in cancer." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/13230/.
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Activation of JAK/STAT signalling is a feature of many haematological malignancies and solid tumours. Better understanding of the molecular events contributing to JAK/STAT pathway activation, and a greater range of therapies acting on the pathway, should lead to improved treatment options for patients with malignancies associated with activation of the pathway. This work builds on screens that identified genes and drugs which modulate JAK/STAT signalling in the fruit fly Drosophila melanogaster, to determine whether these effects occur in the conserved human pathway. The gene ANKHD1 (Ankyrin Repeat and KH Domain containing 1) has been identified as a positive regulator of JAK/STAT signalling in Drosophila, but there has been little investigation of ANKHD1 in human tissues. I show that ANKHD1 protein is expressed in normal blood cells and the malignant clone of cells in acute leukaemias. I also show that ANKHD1 protein is expressed in the skin cancer malignant melanoma, where it is found in the nucleus and cytoplasm in a range of histological sub-types of melanoma. Methotrexate was identified as a selective suppressor of JAK/STAT signalling in a screen in Drosophila cells. No interaction between methotrexate and JAK/STAT signalling has previously been described. I demonstrate that methotrexate suppresses JAK/STAT signalling in human cell lines at drug concentrations equivalent to those measured in patients, suggesting that suppression of JAK/STAT signalling may contribute to the mechanism-of-action of methotrexate in inflammatory conditions. Furthermore, the effect occurs when the pathway is activated by the JAK2V617F mutation found in patients with myeloproliferative neoplasms (MPNs). The potential of methotrexate as a treatment for patients with MPNs is investigated in primary cells obtained from patients with myelofibrosis.
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Blackmore, Malin. "Slöjan och Demokratin : Hör Slöjan Hemma i en Demokratisk Stat?" Thesis, Högskolan i Gävle, Avdelningen för kultur-, religions- och utbildningsvetenskap, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-7288.
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Hör slöjan hemma i en demokratisk stat? Det är inte helt lätt att avgöra eftersom slöjbruket beror på så många olika faktorer. I denna uppsats presenteras bakgrundsfakta om kvinnan i det muslimska samhället, jämställdheten, Islam och demokrati och slöjan i världen. Vad gäller slöjan så är det i grund och botten en sedvänja som inte direkt har med islam att göra. Trots det så väljer många kvinnor att bära den som en symbol för sin religion. I vissa länder är slöjor av olika slag påbud. Många hävdar att slöjan endast är ett medel för att förtrycka kvinnan. Olika påståenden i media analyseras i denna uppsats i relation till demokratins grundpelare: jämlikhet och medborgerlig frihet. I en demokratisk stat torde det vara individens frihet att bära slöja eller inte. Men friheten i samhället kan inte garanteras eftersom man inte vet vilka påtryckningar och oskrivna regler som följer med traditioner och kulturer. Så länge som man inte kan garantera att kvinnor bär slöja av egen fri vilja bör man istället uppmuntra till att alla kvinnor har rätt att synas i samhället. Slutsatsen är att en symbol som ändå står för så mycket negativt hör inte hemma i ett jämlikt samhälle och i en demokratisk stat.
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Kalymbetov, Anuar [Verfasser]. "Role of JAK/STAT signalling pathway in PAH / Anuar Kalymbetov." Gießen : Universitätsbibliothek, 2016. http://d-nb.info/1120270227/34.
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Giedt, Michelle Suzanne. "JAK/STAT SIGNALING REGULATES GAMETOGENESIS AND AGE-RELATED REPRODUCTIVE MAINTENANCE." UKnowledge, 2018. https://uknowledge.uky.edu/biology_etds/52.
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Cell signaling is central to integration of internal and external cues that regulate development and homeostasis. Most development is thought of as pre-adult, but limited developmental processes occur in adults. Gametogenesis incorporates elements of both these facets, with a distinct developmental plan for gamete synthesis which is regulated by integration of homeostatic inputs such as nutrient status, and environmental cues. Signaling pathways integrate and transduce information from these cues to evoke a response. A decline in homeostasis and subsequent cues occurs over time, in the case of reproductive tissues leading to a progressive loss of fertility. The Janus Kinase and Signal Transducer and Activator of Transcription or Jak/Stat signaling pathway is conserved between vertebrates and invertebrates and is necessary for numerous functions needed to maintain organism and reproductive homeostasis, as well as contributing to various developmental events. The pathway in the fruit fly Drosophila melanogaster, is composed of a single receptor, Domeless, one Janus kinase, Hopscotch, one known effector, Stat92E, and the Unpaired family of ligands consisting of Upd, Upd2, and Upd3. Jak/Stat signaling is highly pleiotropic in both sexes with involvement in homeostasis and reproduction, making it an ideal model for studying the role of signaling in reproductive aging. Reduction of pathway activity in females results in a higher proportion of unfertilized eggs, which increases with age, and in males leads to a premature onset of infertility. Central to both is integration through cell signaling to evoke an appropriate response. This dissertation explores two of the requirements for Jak/Stat signaling: the pleiotropic requirement for Jak/Stat activity during oogenesis and male reproductive maintenance.
Jak/Stat functions from the beginning of oogenesis, in the stem cell niche. From there it participates in multiple functions including specification of a subset of somatic cells called the border cells through the polar cells, a pair of cells at either pole of the egg. Pathway stimulation in the border cells drives their migration with the polar cells to the oocyte boundary, where the polar cells each form an extension in a coordinated manner into the micropyle, the means for sperm entrance during fertilization. Loss of Jak/Stat activity in the border cells prevents border cell migration. While border cell migration has been well studied, polar cell involvement after completion of border cell migration is less well known. To investigate the requirements for polar cell activity and Jak/Stat activity after the completion of border cell migration, we reduced Jak/Stat signaling in the polar cells which, while having no effect on border cell migration, results in blocked micropyles due to loss of coordination of extensions during their outgrowth. Reduced function in the polar cells did not significantly affect expression of adhesion molecules. But, the loss of Stat92E is phenocopied by loss of DE-cadherin. Hence, these results indicate a previously unknown autocrine requirement for Jak/Stat activity in the polar cells.
The testes also have a continuous requirement for Jak/Stat activity for stem cell maintenance and differentiation of the germline into mature sperm. Reproductive maintenance not only requires sustained production of gametes, but reproductive tissues are also subject to deterioration of homeostatic functions that contribute to organismal aging. Males from thirty-nine lines of the Drosophila Genetic Reference Panel (DGRP), a panel of inbred, fully sequenced lines, were screened for age at infertility. Data were used to perform a genome-wide association study (GWAS) to identify the genetic architecture of reproductive aging. Candidate variants associated with cell signaling regulators, genes with functions in maintaining cell homeostasis, and organism behavior were uncovered. Notably, several SNPs fell in and near Ptp61F, a negative regulator of Jak/Stat activity. While variants in the primary components of the Jak/Stat pathway were not identified, the general classes of candidate loci functions reflect the requirements for homeostasis, metabolism, and development that have been shown by other studies examining the genetics of aging and fecundity. Thus, we show that Jak/Stat has an amazing amount of pleiotropy that encompasses both the real-time functions of fertility and the time related process of aging.
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Malmgren, Oskar. "Singapore - en diktatur eller en demokrati? : En studie kring Singapores regimtyp." Thesis, Linnéuniversitetet, Institutionen för statsvetenskap (ST), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-59991.
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Singapore är ett fascinerande land. På bara några få decennier har landet gått från att vara en liten instabil stadsstat utan större naturresurser till att bli ett ekonomiskt världscentrum. Mur hur fungerar egentligen Singapores politiska styrelseskick? Är landet verkligen en demokrati eller har det i själva verket diktatoriska drag? Denna uppsats syftar till att steg för steg undersöka landets politiska situation för att slutligen landa i en definition om vad Singapore egentligen står politiskt. Dem styrande hävdar att dem levererar en effektiv och okorrumperad regering till medborgarna medan vissa oppositionspolitiker menar att regeringen styr med auktoritära medel. Hur kan man definiera den politiska situationen i Singapore idag och framför allt vilken regimtyp kan landet klassas som? Detta arbete är en fallstudie av teorikonsumerande art där olika fakta kommer att analyseras och sedan sammanfattas i en slutlig analys där jag skall fastställa regimtypen.
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Žalinkevičiūtė, Odeta. "STAT 5 geno aptikimas ir jo polimorfizmo nustatymas Lietuvoje veisiamose galvijų veislėse." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2008. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2008~D_20080319_131328-37428.
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Darbo tikslas - ištirti STAT 5 geno įvairovę Lietuvoje auginamų galvijų tarpe. LVA Gyvūnų genetikos laboratorijoje įdiegta galvijų STAT 5 geno, ištyrimo metodika. Pirmą kartą ištirtas STAT 5 geno polimorfizmas Lietuvoje auginamų galvijų tarpe Darbo uždaviniai: 1. Surinkti ir išanalizuoti mokslinę literatūrą apie mėsinių galvijų STAT 5 geną ir ištirti jo įtaką produktyviosioms savybėms, ieškoti straipsnių internetinėse svetainėse nagrinėjama tema; 2. Įdiegti galvijų STAT 5 geno tyrimo metodiką LVA K.Janušausko Gyvūnų genetikos laboratorijoje; 3. Ištirti STAT 5 geno įvairovę Lietuvoje auginamų galvijų tarpe, naudojant sumodeliuotus pradmenis pagal geno seką; 4. Nustatyti STAT 5 geno aleli�� ir genotipų dažnius skirtingose galvijų veislėse.Object and tasks of work. Analyse and summarize literature about STAT 5 gene in cattle. Introduce bovine STAT 5 gene research methodology at K. Janušauskas Laboratory of Animal Genetics, LVA..Investigate STAT 5 gene polymorphism and distribution of different alleles and genotypes in cattle breeds bred in Lithuania. Research methodology. DNA extraction from hair roots; PGR to amplify STAT 5 gene; RFLP method-STAT 5 – enzyme AvaI; Electrophoresis in agarose gel; Staining with etidium bromide; Genotyping; Statistical analysis of data. Results and conclusions. Two alleles C and T were found in tested cattle group identified by PGR-RFLP method. There was found a bit lower heterozigosity than expected in STAT 5 gene locus. The frequency of C allele was 0,89, T allele – 0,11, CC genotipe – 0,79, Ct genotipe -0,21. TT genotipe was not found. In all tested cattle breeds prevailing was found C allele and CC genotipe varying from 50 percent in Sharole breed to 100 percent in simental breed. CT heterozygote genotipe in pargest frequency 0,5 found in Sharole breed and lowest frequency 0,03 in Lithuanian black and white.
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Litterst, Claudia Monika. "Untersuchungen zur Funktion von Koaktivatoren in der JAK-STAT-vermittelten Transkriptionsaktivierung." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966005597.
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Ihse, Cecilia. "Präst, stånd och stat : Kung och kyrka i förhandling 1642-1686." Doctoral thesis, Stockholms universitet, Historiska institutionen, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-437.
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This dissertation is the result of a study of power relations between the crown and the church in Sweden during the 17th century. The study is focused on the Swedish Parliament and how the Estate of the Clergy responded to royal pretensions. The Swedish Clerical Estate is viewed as essential for the Swedish state formation process. The argument in the study is inspired by theories suggesting that state building and state formation were outcomes of a bargaining process between rulers and local power holders. The perspective presented by the historian Jan Glete is of great importance. He defines the early modern state as a complex organization providing protection and violence control. He emphasizes that the power of the state and the state’s character were dependent upon how the state could assert power. In order to do this, the rulers bartered with their subjects using protection as a commodity while in return the subjects paid required taxes. This bargaining process is interpreted as interactive. The rulers linked various local interests to the state and in doing so gained control of the society and the use of violence. The Swedish Clerical Estate played an important role in this process. Due in part to this fact, the clergy differed from the other subjects of the realm such as the nobility or the peasants. The clergy did not own any sizeable amount of property and did not exert any economical influence. Instead the Clerical Estate negotiated using their ideological, cultural and political resources. These commodities became essential in how the king organized the state. In exchange for royal protection, the clergy were given the task of supporting and explaining the crown’s economical and military needs. By doing so, the Clerical Estate legitimated the royal power in the parliament and in the society as a whole. At the same time, this negotiation signified a definition of the role of the clergyman within the state. Though the Clerical Estate sometimes tried to reject royal claims, it was the king who decided the conditions of negotiation. The parliament as a political field was created by the king and for the king. From a political point of view, religion and a theological framework became of great importance and were adopted by the crown in order to exploit resources. Taking this into consideration, the 17th century Swedish state seems to be more effective than other European early modern states.