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"Kunst-Leben". Der Einfluss der russischen "religiösen Renaissance" auf die Ästhetik und Kunst des Spätsymbolismus zu Beginn des 20. Jahrhunderts in Russland.Sadykowa, Elena 10 February 2005 (has links)
Die vorliegende Arbeit befasst sich mit dem Phänomen der neuchristlichen Kunst in Russland nach der Oktober-Revolution 1917. Es gilt hier die philosophischen, geistesgeschichtlichen und kunsthistorischen Hintergründe zu erforschen, die zur Erscheinung der spätsymbolistischen Künstlervereinigung Kunst-Leben bzw. Makowez geführt haben. Dabei handelt es sich um eine scheinbar unzeitgemäße Vereinigung, deren Mitglieder sich den zeitgenössischen nihilistischen Tendenzen der russischen Kunst zum Trotz - den geistigen Traditionen der Weltkultur zuwandten. In ihren Kunstwerken thematisierten sie die Probleme der Religion, Mythologie, Spiritualität. In ihrem Manifest proklamierten sie die Entwicklung einer neuen, universellen Kunst, die als wahres Schöpfertum das Leben selbst erschaffen sollte. Das Anliegen der Verfasserin besteht darin, die Ursprünge dieses damals so untypischen Denkens in Russland zu nachvollziehen. Diese liegen in einem kulturhistorischen Phänomen der Jahrhundertwende vom 19. zum 20. Jahrhundert, das als russische religiöse Renaissance in die Kulturgeschichte Russlands eingegangen ist. Im ersten Kapitel werden die Voraussetzungen für die Entstehung dieses Phänomens aufgezeigt, welche die Verfasserin von der Ästhetik des deutschen Idealismus und von der Gesinnung der deutschen Romantik ableitet. Im zweiten Kapitel werden die genuin russischen symbolistisch-neuchristlichen ästhetischen Konzepte abgehandelt, die auf die ästhetischen Vorstellungen der russischen Künstler zu Beginn des 20. Jahrhunderts einen großen Einfluss ausübten. Dieser Einfluss ist das Thema des dritten Kapitels dieser Arbeit, in dem es um die theoretischen Auseinandersetzungen der russischen bildenden Künstler geht. Die vorliegende Dissertation trägt dazu bei, ein klareres Bild der damaligen Epoche der zwanziger Jahre in Russland zu gewinnen und ermöglicht ein tieferes Verständnis der Entstehung und Entwicklung der symbolistischen Weltanschauung in Russland.
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The EU General Data Protection Regulations and their consequences on computer system design / EUs allmänna dataskyddsförordning och dess konsekvenser för programsystemteknikMagnusson, Wilhelm January 2017 (has links)
As of writing this thesis, the EU’s new data protection laws (GDPR) will start to apply within one year. The new regulations are poorly understood by many and rumours of varying accuracy are circling the IT industry. This thesis takes a look at the parts of the GDPR concerning system design and architecture, clarifying what they mean and their consequences for system design. The new regulations are compared to the old data protection laws (Directive 95/46/EC), showing how companies must alter their computer systems in order to adapt. Using evaluations of the old data protection laws predictions are made for how the GDPR will affect the IT industry going forward. One of the more important questions are what tools are available for companies when adapting to privacy protection regulations and threats. This thesis aims to identify the most common processes for this kind of system modification and compare their effectiveness in relation to the GDPR. / Vid framställningen av denna avhandling är det mindre än ett år innan EUs nya dataskyddsförordning (GDPR) träder i kraft. Många har bristande förståelse av de nya förordningarna och rykten av varierande korrekthet cirkulerar inom IT industrin. Denna avhandling utför en kritisk undersökning utav de delar inom GDPR som berör system design och arkitektur och beskriver dess innebörd för system design. De nya lagarna jämförs med de föregående dataskyddslagarna (Direktiv 95/46/EC) för att påvisa de modifikationer som kommer krävas för att anpassa datorsystem till de nya förordningarna. Genom att undersöka de äldre dataskyddslagarnas effekt på industrin görs även förutsägelser kring hur GDPR kommer påverka IT industrin inom den närmaste framtiden. Än av de intressantare frågorna är vilka metoder som finns tillgängliga för att underlätta systemanpassningar relaterade till dataskyddsförordningar. Denna avhandling syftar att identifiera de mest etablerade av dessa typer av processer och jämföra deras lämplighet i förhållande till GDPR.
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La deuxième venue du Seigneur (parousie) d'après Paul et son application dans la théologie contemporaineCalderon, Mario Francisco 08 1900 (has links)
Le présent mémoire a comme sujet l'analyse et la caractérisation de la pensée de Paul sur la parousie (la deuxième venue du Seigneur) et l'étude de l'interprétation de cette pensée dans la théologie contemporaine,telle que représentée par Rudolf Bultmann, tenant de la démythologisation, et les théologiens de la libération Ignacio Ellacuria et Jon Sobrino. Les éléments clés de la parousie sont décrits principalement en Matthieu 25,31-46, 1 Cor 15,20-28, 1 Thess 4,13-18, 2 Thess 2,1-12. D'après Paul, « Le Seigneur, au signal donné, à la voix de l'archange et au son de la trompette de Dieu, descendra du ciel ». La principale question du mémoire porte sur cette vision paulinienne: Est-ce que la deuxième venue du Seigneur d'après la description paulinienne est encore crédible pour l'homme contemporain ou est-ce qu'il s'agit d'un élément mythologique non essentiel à la foi chrétienne? Bultmann considère que la parousie est un mythe : à ce jour, la parousie ne s'est pas produite, et elle ne se produira jamais. Le kérygme est le seul élément que Bultmann considère comme valide. « The kerygma is the proclamation of the decisive act of God in Christ ». Par contraste, Ellacuria est d'avis que l'élément eschatologique est essentiel pour comprendre l'histoire, car cette dernière est orientèe vers la fin. De manière analogue, Sobrino présente le Royaume de Dieu comme étant un élément clé de l'eschatologie. La théologie de la libération présente également la parousie comme un élément à venir qui représente l'implantation intégrale du Royaume de Dieu et qui devrait se comprendre comme une perspective eschatologique au-delà de l'imagerie de la parousie. / The subject of this thesis is the analysis and the characterization of Paul's doctrine on the parousia (the second coming) of Jesus, and the study of the interpretation of the parousia by the contemporary theologians, such as Rudolf Bultmann, the representative of the demythologization and the theologians of the liberation, Ignacio Ellacuria and Jon Sobrino. The key elements of the New Testament's doctrine of the parousia are described in Matthew 25,31-46, 1 Cor 15,20-28,1 Thess 4, 13-18 and 2 Thess 2,1-12. According to Paul, « There will be the shout of command, the archangel's voice, the sound of God's trumpet, and the Lord himself will come down from heaven ».The key question is: What do the contemporary men and women think of this doctrine? Is the second coming of Jesus according to Paul's description still believable to contemporary persons or is it rather a mythical element non essential to the Christian faith? Bultmann sees the parousia as a mythical issue. The parousia has not happened until now, and it will never occur. The only element that Bultmann proposes as valid is the kerygma. « The kerygma is the proclamation of the decisive act of God in Christ ». Ellacuria on the contrary, believes that the eschatological element is essential to understand history, which itself is oriented towards the end of time. Sobrino in a similar way, proposes the Kingdom of God as a key element of the eschatology. The theology of liberation presents as well the parousia like a future event, representing the integral implementation of the Kingdom of God, which should be understood as an eschatological perspective going further than the imagery of the parousia.
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Participação de proteínas da via secretória no tráfego e montagem do vírus sincicial respiratório / Participation of proteins in secretory route traffic and assembling of respiratory syncytial virusCardoso, Ricardo de Souza 11 March 2016 (has links)
O vírus sincicial respiratório humano (HRSV) é o mais frequente agente patogênico da família Paramyxoviridae. Apesar de sua grande importância e impacto em saúde pública, alguns aspectos demandam elucidação. Entre eles, estão os mecanismos de tráfego intracelular de proteínas virais para o sitio de montagem. Baseado nisso, fizemos um estudo de imunofluorescência tentando contribuir para o entendimento da participação da via secretória no tráfego de proteínas estruturais de HRSV que não são glicosiladas: proteínas de matriz (M) e de nucleocapsídeo (N). Pudemos observar que essas proteínas seguem rota similar àquelas que são glicosiladas no Golgi, como a proteína de fusão (F). Ademais, as proteínas M e N, além de colocalizarem com proteínas celulares da via secretória, tais como trans-Golgi network-46 (TGN46) e sorting nexin-2 (SNX2), também influem no recrutamento de proteínas celulares para os corpos de inclusão virais, como mostrado no caso da proteína Glut1. Os dados indicam que proteínas M e N de HRSV seguem pela via endocítica inicial, acumulam-se em corpos de inclusão que seriam fábricas virais e, no caso de TGN46, podem ser incorporadas aos vírus em brotamento / Human respiratory syncytial virus (HRSV) is the most relevant cause of respiratory infection in children worldwide. Despite its importance in public health, some aspects of the mechanisms of the trafficking of viral structural proteins remain unclear. In the present study, immunofluorescence was used to understand how the virus matrix (M) and nucleocapsid (N) proteins, which are non-glycosylated , are addressed to inclusion bodies in Hep-2 cells (MOI=3). M and N proteins followed similar intracellular trafficking routes as compared to the glycosylated fusion (F) viral protein. Moreover, M and N proteins colocalized with two key elements of the secretory pathway: trans-Golgi network- 46 (TGN46) and sorting nexin-2 (SNX2). Viral proteins M and N appear to be involved in the recruitment of cell proteins at the formation of virus inclusion bodies, as shown for Glucose Transporter Type 1 (Glut1). The data suggest that HRSV M and N proteins follow the secretory pathway, initiating in early endosomes, as indicated by the co-localization with TGN46 and SNX2. In addition, these host cell proteins accumulate in inclusion bodies that are viral factories, and can be part of budding viral progeny. Therefore, HRSV M and N proteins, even though they are not glycosylated, take advantage of the secretory pathway to reach virus inclusion bodies. Confocal images suggest that SNX2, which is known for its membrane-deforming properties, could play a pivotal role in HRSV budding
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Distúrbio do desenvolvimento sexual 46,XX testicular SRY negativo sindrômico devido à mutação missense no gene RSPO1: estudo clínico, molecular e histológico de grande família consanguínea brasileira / SRY-negative syndromic 46,XX testicular disorder of sex development due to missense homozygous RSPO1 mutation: clinical, molecular and histological study of a large consanguineous Brazilian familySilva, Rosana Barbosa 22 October 2015 (has links)
Nos mamíferos, a determinação sexual é governada pelo equilíbrio entre duas vias de sinalização paralelas e antagônicas: a via masculina SOX9/FGF9 e a via feminina RSPO1/beta-catenina/WNT4. A R-spondina 1 é uma importante reguladora do processo de diferenciação ovariana e atua modulando a via de sinalização Wnt canônica (Wnt/beta-catenina). Em humanos, mutações em RSPO1 causam uma rara síndrome genética autossômica recessiva caracterizada por Distúrbios do Desenvolvimento Sexual (DDS) 46,XX Testicular ou Ovotesticular, hiperceratose palmoplantar (HPP) e predisposição para o desenvolvimento de carcinoma de células escamosas (MIM 610644). Identificamos um paciente brasileiro, proveniente de uma grande família consanguínea, que apresentava a associação de HPP e DDS 46,XX Testicular SRY negativo. A avaliação da região codificadora do gene RSPO1 identificou a nova variante alélica c.305G>A (p.Cys102Tyr). O estudo de segregação realizado em 67 familiares demonstrou que a variante c.305G>A segrega em perfeita concordância com o fenótipo de HPP, exibindo um padrão de herança autossômico recessivo. Na família foram identificados 10 indivíduos afetados pelo fenótipo de HPP. As avaliações clínica e hormonal e os estudos molecular e citogenético nesses indivíduos resultou na caracterização de: (a) quatro indivíduos do sexo masculino 46,XX e/ou SRY negativo, com ambiguidade genital e perfil hormonal alterado; (b) cinco indivíduos do sexo masculino 46,XY e/ou SRY positivo, sem ambiguidade genital, com perfil hormonal normal e (c) uma mulher 46,XX, fértil. Experimentos de transfecção transitória in vitro demostraram que a proteína mutante tem menor capacidade de transativação do plasmídio reporter da via Wnt. As simulações de dinâmica molecular constataram que a troca p.Cys102Tyr aumenta a flexibilidade do backbone da R-spondina-1, diminuindo a energia de ligação da proteína ao complexo de receptores, LGR5 e RNF43. Em conjunto, nossos achados demonstram que a variante c.305G > A é patogênica, sendo responsável pela síndrome genética diagnosticada na família brasileira. As análises de expressão gênica e os estudos de imuno-histoquímica, por sua vez, detectaram um aumento da expressão do gene SOX9 e maior imonorreatividade para a proteína Sox9 no tecido testicular do caso índice. Esses resultados sugerem que o processo de reversão sexual nos indivíduos XX ocorra por uma hiperexpressão de SOX9 secundária à menor ativação da via Wnt/beta-catenina na gônada durante a embriogênese. No presente estudo também relatamos o primeiro caso de indivíduo de cariótipo 46,XX portador de mutação em homozigose no gene RSPO1 que não desenvolveu DDS. A variabilidade do fenótipo sexual não está associada com alterações no número de cópias dos genes WNT4 ou do SOX9 e região cis-regulatória. No entanto, a avaliação do exoma da família encontrou uma associação entre o polimorfismo do receptor LGR5 rs17109924 e a atenuação do fenótipo de DDS. Todavia, serão necessários estudos funcionais para esclarecer o impacto biológico da interação das variantes RSPO1 p.Cys102Tyr e LGR5 rs171099 / In mammals, sex determination is governed by the balance between two parallel and antagonic signaling pathways: the male SOX9/FGF9 and the female, RSPO1/beta-catenin/WNT4 pathways. R-spondin 1 regulates the ovarian differentiation process by its modulating action through the canonic Wnt pathway (Wnt/beta-catenin). In humans, patogenic mutations in RSPO1 cause a rare, autosomic recessive syndrome characterized by 46,XX Testicular or Ovotesticular disorders of sexual development (DSD), palmoplantar keratosis (PPK) and predisposition to squamous cell carcinoma (MIM 610644). We identified and studied a SRY-negative 46,XX DSD patient with PPK from a large, consaguineous, brazillian family. Through a \"candidate gene\" approach we identified in the proband a new allelic variant in the coding region of RSPO1, c.305G > A. This variant presented full concordance with the PPK phenotype by segregation analyses in 10 of 67 members of this family. Clinical, hormonal, cytogenetic and molecular genetic studies characterized three patterns in individuals with this variant: (a) four 46,XX and/or SRY-negative males with ambiguous genitalia and altered hormonal profile; (b) five 46,XY and/or SRY-positive males without ambiguous genitalia with normal hormonal profile; (c) one 46,XX fertile woman. In vitro experiments demonstrated that transient transfection of the mutant protein resulted in lower transactivation of the Wnt pathway-reporter plasmid. Moreover, molecular dinamic studies showed that p.Cys102Tyr increased the R-spondin-1 backbone flexibility, thus decreasing the interaction between this protein and its receptors, LGR5 and RNF43. Thus, both in vitro and in silico analysis demonstrate the pathogenicity of the RSPO1 variant c.305G > A. In addition, in the index case, a higher expression of SOX9, corroborated by a reactive immunohistochemistry in testicular tissue, suggested that the process of sexual reversal in the XX individual is driven by a higher SOX9 expression possibly due to a lower Wnt/beta-catenin signaling pathway activation during embriogenesis. In this study, we also reported the first 46,XX individual with RSPO1 mutation without DSD, in which no copy number abnormality was detected in WNT4, SOX9 and its cisregulatory regions. Whole exome sequencing of the affected individuals revealed, in turn, that the LGR5 rs17109924 polymorphism associates with a protacted DSD phenotype in the fertile woman with normal hormonal profile. Despite this evidence, future studies are nedded to address causality and biological impact between RSPO1 p.Cys102Tyr and LGR5 rs17109924 variants
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La deuxième venue du Seigneur (parousie) d'après Paul et son application dans la théologie contemporaineCalderon, Mario Francisco 08 1900 (has links)
Le présent mémoire a comme sujet l'analyse et la caractérisation de la pensée de Paul sur la parousie (la deuxième venue du Seigneur) et l'étude de l'interprétation de cette pensée dans la théologie contemporaine,telle que représentée par Rudolf Bultmann, tenant de la démythologisation, et les théologiens de la libération Ignacio Ellacuria et Jon Sobrino. Les éléments clés de la parousie sont décrits principalement en Matthieu 25,31-46, 1 Cor 15,20-28, 1 Thess 4,13-18, 2 Thess 2,1-12. D'après Paul, « Le Seigneur, au signal donné, à la voix de l'archange et au son de la trompette de Dieu, descendra du ciel ». La principale question du mémoire porte sur cette vision paulinienne: Est-ce que la deuxième venue du Seigneur d'après la description paulinienne est encore crédible pour l'homme contemporain ou est-ce qu'il s'agit d'un élément mythologique non essentiel à la foi chrétienne? Bultmann considère que la parousie est un mythe : à ce jour, la parousie ne s'est pas produite, et elle ne se produira jamais. Le kérygme est le seul élément que Bultmann considère comme valide. « The kerygma is the proclamation of the decisive act of God in Christ ». Par contraste, Ellacuria est d'avis que l'élément eschatologique est essentiel pour comprendre l'histoire, car cette dernière est orientèe vers la fin. De manière analogue, Sobrino présente le Royaume de Dieu comme étant un élément clé de l'eschatologie. La théologie de la libération présente également la parousie comme un élément à venir qui représente l'implantation intégrale du Royaume de Dieu et qui devrait se comprendre comme une perspective eschatologique au-delà de l'imagerie de la parousie. / The subject of this thesis is the analysis and the characterization of Paul's doctrine on the parousia (the second coming) of Jesus, and the study of the interpretation of the parousia by the contemporary theologians, such as Rudolf Bultmann, the representative of the demythologization and the theologians of the liberation, Ignacio Ellacuria and Jon Sobrino. The key elements of the New Testament's doctrine of the parousia are described in Matthew 25,31-46, 1 Cor 15,20-28,1 Thess 4, 13-18 and 2 Thess 2,1-12. According to Paul, « There will be the shout of command, the archangel's voice, the sound of God's trumpet, and the Lord himself will come down from heaven ».The key question is: What do the contemporary men and women think of this doctrine? Is the second coming of Jesus according to Paul's description still believable to contemporary persons or is it rather a mythical element non essential to the Christian faith? Bultmann sees the parousia as a mythical issue. The parousia has not happened until now, and it will never occur. The only element that Bultmann proposes as valid is the kerygma. « The kerygma is the proclamation of the decisive act of God in Christ ». Ellacuria on the contrary, believes that the eschatological element is essential to understand history, which itself is oriented towards the end of time. Sobrino in a similar way, proposes the Kingdom of God as a key element of the eschatology. The theology of liberation presents as well the parousia like a future event, representing the integral implementation of the Kingdom of God, which should be understood as an eschatological perspective going further than the imagery of the parousia.
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Markus syn på blindhet : Analys av en metafor, dess funktion och dysfunktionSernheim, Jacob January 2015 (has links)
This essay examines the theme of blindness in the Gospel of Mark. The two main questions asked are: 1) “What is Mark’s view on blindness?” and 2) “How does the Gospel of Mark’s view on blindness inform the current discourse of disability studies and how can we interpret Mark’s view on blindness today?” By the methods of metaphor analysis and character analysis, four passages of the Gospel are studied (Mark 4:10-12; 8:14-21; 22-26; 10:46-52). The analysis concludes that blindness is depicted by the author of the Gospel as a disability which also consist of a lack of cognitive ability and a hopeless state that is in need of healing. The depiction of blindness in Mark originates out of the authors use of blindness as a metaphor for lack of cognitive ability (Mk 4:12; 8:18) and the lack of characterization of the blind man at Bethsaida (8:22-23). This view on blindness is, in comparison to a modern view, difficult, as it marginalizes persons with blindness as inconsiderate and not fully human. The view of blindness is somewhat nuanced, however, by the fuller characterization of Bartimaeus (10:46-52). The essay then discusses, in dialogue with disability studies, the complexity of Mark’s uses of blindness as a metaphor and of the difficulties of our modern, often generalized, views of blindness in antiquity and how the view of blindness in Marks gospel both constructs and deconstructs blindness as a disability.
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Distúrbio do desenvolvimento sexual 46,XX testicular SRY negativo sindrômico devido à mutação missense no gene RSPO1: estudo clínico, molecular e histológico de grande família consanguínea brasileira / SRY-negative syndromic 46,XX testicular disorder of sex development due to missense homozygous RSPO1 mutation: clinical, molecular and histological study of a large consanguineous Brazilian familyRosana Barbosa Silva 22 October 2015 (has links)
Nos mamíferos, a determinação sexual é governada pelo equilíbrio entre duas vias de sinalização paralelas e antagônicas: a via masculina SOX9/FGF9 e a via feminina RSPO1/beta-catenina/WNT4. A R-spondina 1 é uma importante reguladora do processo de diferenciação ovariana e atua modulando a via de sinalização Wnt canônica (Wnt/beta-catenina). Em humanos, mutações em RSPO1 causam uma rara síndrome genética autossômica recessiva caracterizada por Distúrbios do Desenvolvimento Sexual (DDS) 46,XX Testicular ou Ovotesticular, hiperceratose palmoplantar (HPP) e predisposição para o desenvolvimento de carcinoma de células escamosas (MIM 610644). Identificamos um paciente brasileiro, proveniente de uma grande família consanguínea, que apresentava a associação de HPP e DDS 46,XX Testicular SRY negativo. A avaliação da região codificadora do gene RSPO1 identificou a nova variante alélica c.305G>A (p.Cys102Tyr). O estudo de segregação realizado em 67 familiares demonstrou que a variante c.305G>A segrega em perfeita concordância com o fenótipo de HPP, exibindo um padrão de herança autossômico recessivo. Na família foram identificados 10 indivíduos afetados pelo fenótipo de HPP. As avaliações clínica e hormonal e os estudos molecular e citogenético nesses indivíduos resultou na caracterização de: (a) quatro indivíduos do sexo masculino 46,XX e/ou SRY negativo, com ambiguidade genital e perfil hormonal alterado; (b) cinco indivíduos do sexo masculino 46,XY e/ou SRY positivo, sem ambiguidade genital, com perfil hormonal normal e (c) uma mulher 46,XX, fértil. Experimentos de transfecção transitória in vitro demostraram que a proteína mutante tem menor capacidade de transativação do plasmídio reporter da via Wnt. As simulações de dinâmica molecular constataram que a troca p.Cys102Tyr aumenta a flexibilidade do backbone da R-spondina-1, diminuindo a energia de ligação da proteína ao complexo de receptores, LGR5 e RNF43. Em conjunto, nossos achados demonstram que a variante c.305G > A é patogênica, sendo responsável pela síndrome genética diagnosticada na família brasileira. As análises de expressão gênica e os estudos de imuno-histoquímica, por sua vez, detectaram um aumento da expressão do gene SOX9 e maior imonorreatividade para a proteína Sox9 no tecido testicular do caso índice. Esses resultados sugerem que o processo de reversão sexual nos indivíduos XX ocorra por uma hiperexpressão de SOX9 secundária à menor ativação da via Wnt/beta-catenina na gônada durante a embriogênese. No presente estudo também relatamos o primeiro caso de indivíduo de cariótipo 46,XX portador de mutação em homozigose no gene RSPO1 que não desenvolveu DDS. A variabilidade do fenótipo sexual não está associada com alterações no número de cópias dos genes WNT4 ou do SOX9 e região cis-regulatória. No entanto, a avaliação do exoma da família encontrou uma associação entre o polimorfismo do receptor LGR5 rs17109924 e a atenuação do fenótipo de DDS. Todavia, serão necessários estudos funcionais para esclarecer o impacto biológico da interação das variantes RSPO1 p.Cys102Tyr e LGR5 rs171099 / In mammals, sex determination is governed by the balance between two parallel and antagonic signaling pathways: the male SOX9/FGF9 and the female, RSPO1/beta-catenin/WNT4 pathways. R-spondin 1 regulates the ovarian differentiation process by its modulating action through the canonic Wnt pathway (Wnt/beta-catenin). In humans, patogenic mutations in RSPO1 cause a rare, autosomic recessive syndrome characterized by 46,XX Testicular or Ovotesticular disorders of sexual development (DSD), palmoplantar keratosis (PPK) and predisposition to squamous cell carcinoma (MIM 610644). We identified and studied a SRY-negative 46,XX DSD patient with PPK from a large, consaguineous, brazillian family. Through a \"candidate gene\" approach we identified in the proband a new allelic variant in the coding region of RSPO1, c.305G > A. This variant presented full concordance with the PPK phenotype by segregation analyses in 10 of 67 members of this family. Clinical, hormonal, cytogenetic and molecular genetic studies characterized three patterns in individuals with this variant: (a) four 46,XX and/or SRY-negative males with ambiguous genitalia and altered hormonal profile; (b) five 46,XY and/or SRY-positive males without ambiguous genitalia with normal hormonal profile; (c) one 46,XX fertile woman. In vitro experiments demonstrated that transient transfection of the mutant protein resulted in lower transactivation of the Wnt pathway-reporter plasmid. Moreover, molecular dinamic studies showed that p.Cys102Tyr increased the R-spondin-1 backbone flexibility, thus decreasing the interaction between this protein and its receptors, LGR5 and RNF43. Thus, both in vitro and in silico analysis demonstrate the pathogenicity of the RSPO1 variant c.305G > A. In addition, in the index case, a higher expression of SOX9, corroborated by a reactive immunohistochemistry in testicular tissue, suggested that the process of sexual reversal in the XX individual is driven by a higher SOX9 expression possibly due to a lower Wnt/beta-catenin signaling pathway activation during embriogenesis. In this study, we also reported the first 46,XX individual with RSPO1 mutation without DSD, in which no copy number abnormality was detected in WNT4, SOX9 and its cisregulatory regions. Whole exome sequencing of the affected individuals revealed, in turn, that the LGR5 rs17109924 polymorphism associates with a protacted DSD phenotype in the fertile woman with normal hormonal profile. Despite this evidence, future studies are nedded to address causality and biological impact between RSPO1 p.Cys102Tyr and LGR5 rs17109924 variants
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Participação de proteínas da via secretória no tráfego e montagem do vírus sincicial respiratório / Participation of proteins in secretory route traffic and assembling of respiratory syncytial virusRicardo de Souza Cardoso 11 March 2016 (has links)
O vírus sincicial respiratório humano (HRSV) é o mais frequente agente patogênico da família Paramyxoviridae. Apesar de sua grande importância e impacto em saúde pública, alguns aspectos demandam elucidação. Entre eles, estão os mecanismos de tráfego intracelular de proteínas virais para o sitio de montagem. Baseado nisso, fizemos um estudo de imunofluorescência tentando contribuir para o entendimento da participação da via secretória no tráfego de proteínas estruturais de HRSV que não são glicosiladas: proteínas de matriz (M) e de nucleocapsídeo (N). Pudemos observar que essas proteínas seguem rota similar àquelas que são glicosiladas no Golgi, como a proteína de fusão (F). Ademais, as proteínas M e N, além de colocalizarem com proteínas celulares da via secretória, tais como trans-Golgi network-46 (TGN46) e sorting nexin-2 (SNX2), também influem no recrutamento de proteínas celulares para os corpos de inclusão virais, como mostrado no caso da proteína Glut1. Os dados indicam que proteínas M e N de HRSV seguem pela via endocítica inicial, acumulam-se em corpos de inclusão que seriam fábricas virais e, no caso de TGN46, podem ser incorporadas aos vírus em brotamento / Human respiratory syncytial virus (HRSV) is the most relevant cause of respiratory infection in children worldwide. Despite its importance in public health, some aspects of the mechanisms of the trafficking of viral structural proteins remain unclear. In the present study, immunofluorescence was used to understand how the virus matrix (M) and nucleocapsid (N) proteins, which are non-glycosylated , are addressed to inclusion bodies in Hep-2 cells (MOI=3). M and N proteins followed similar intracellular trafficking routes as compared to the glycosylated fusion (F) viral protein. Moreover, M and N proteins colocalized with two key elements of the secretory pathway: trans-Golgi network- 46 (TGN46) and sorting nexin-2 (SNX2). Viral proteins M and N appear to be involved in the recruitment of cell proteins at the formation of virus inclusion bodies, as shown for Glucose Transporter Type 1 (Glut1). The data suggest that HRSV M and N proteins follow the secretory pathway, initiating in early endosomes, as indicated by the co-localization with TGN46 and SNX2. In addition, these host cell proteins accumulate in inclusion bodies that are viral factories, and can be part of budding viral progeny. Therefore, HRSV M and N proteins, even though they are not glycosylated, take advantage of the secretory pathway to reach virus inclusion bodies. Confocal images suggest that SNX2, which is known for its membrane-deforming properties, could play a pivotal role in HRSV budding
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O poder das idéias: a construção e a demolição da imagem presidencial de Carlos LacerdaOliveira, André Lopes de 21 May 2018 (has links)
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Previous issue date: 2018-05-21 / O presente trabalho trata da análise da construção e demolição da imagem presidencial de Carlos Lacerda, jornalista, vereador da cidade do Rio de Janeiro, deputado federal, governador da Guanabara e pré-candidato às eleições presidenciais, previstas para ocorrer em 1965, ano em que se encerrava seu mandato como governador. Tratamos da maneira como Lacerda utilizou o período à frente da Guanabara como plataforma para construir sua candidatura, e de como ela foi afetada pelo movimento civil-militar ocorrido em 31 de março de 1964, que levou à deposição do presidente João Goulart e à instauração de um regime militar no Brasil. / Ce travail présente une analyse de la construction et de la démolition de l’image présidentielle de Carlos Lacerda, journaliste, conseiller municipal de Rio de Janeiro, député fédéral, gouverneur de la Guanabara, et pré-candidat aux élections présidentielles, qui devraient avoir lieu en 1965, l’année où finissait son mandat comme gouverneur. On étudie la manière dont Lacerda a profité de la période comme chef politique de la Guanabara comme une plateforme pour construire sa candidature et comment celle-ci a été atteinte par le mouvement civil-militaire du 31 mars 1964, qui a déposé le président João Goulart et a instauré un régime militaire au Brésil.
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