996 resultados para -Er^3
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Although the pathology of Morbillivirus in the central nervous system (CNS) is well described, the molecular basis of neurodegenerative events still remains poorly understood. As a model to explore Morbillivirus-mediated CNS dysfunctions, we used canine distemper virus (CDV) that we inoculated into two different cell systems: a monkey cell line (Vero) and rat primary hippocampal neurons. Importantly, the recombinant CDV used in these studies not only efficiently infects both cell types but recapitulates the uncommon, non-cytolytic cell-to-cell spread mediated by virulent CDVs in brain of dogs. Here, we demonstrated that both CDV surface glycoproteins (F and H) markedly accumulated in the endoplasmic reticulum (ER). This accumulation triggered an ER stress, characterized by increased expression of the ER resident chaperon calnexin and the proapoptotic transcription factor CHOP/GADD 153. The expression of calreticulin (CRT), another ER resident chaperon critically involved in the response to misfolded proteins and in Ca(2+) homeostasis, was also upregulated. Transient expression of recombinant CDV F and H surface glycoproteins in Vero cells and primary hippocampal neurons further confirmed a correlation between their accumulation in the ER, CRT upregulation, ER stress and disruption of ER Ca(2+) homeostasis. Furthermore, CDV infection induced CRT fragmentation with re-localisation of a CRT amino-terminal fragment, also known as vasostatin, on the surface of infected and neighbouring non-infected cells. Altogether, these results suggest that ER stress, CRT fragmentation and re-localization on the cell surface may contribute to cytotoxic effects and ensuing cell dysfunctions triggered by Morbillivirus, a mechanism that might potentially be relevant for other neurotropic viruses.
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Objectives: A study was made to determine the temperature increment at the dental root surface following Er,Cr:YSGG laser irradiation of the root canal. Design. Human canines and incisors previously instrumented to K file number ISO 30 were used. Irradiation was carried out with glass fiber endodontic tips measuring 200 m in diameter and especially designed for insertion in the root canal. The teeth were irradiated at 1 and 2 W for 30 seconds, without water spraying or air, and applying a continuous circular movement (approximately 2 mm/sec.) in the apico-coronal direction. Results: At the 1 W power setting, the mean temperature increment was 3.84C versus 5.01C at 2 W. In all cases the difference in mean value obtained after irradiation versus the mean baseline temperature proved statistically significant (p< 0.05). Conclusions: Application of the Er,Cr:YSGG laser gives rise to a statistically significant temperature increment at the external root surface, though this increment is probably clinically irrelevant, since it would appear to damage the tissues (periodontal ligament and alveolar bone) in proximity to the treated tooth
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The inhibition of phosphatidic acid phosphatase (PAP) activity by propanolol indicates that diacylglycerol (DAG) is required for the formation of transport carriers at the Golgi and for retrograde trafficking to the ER. Here we report that the PAP2 family member lipid phosphate phosphatase 3 (LPP3, also known as PAP2b) localizes in compartments of the secretory pathway from ER export sites to the Golgi complex. The depletion of human LPP3: (i) reduces the number of tubules generated from the ER-Golgi intermediate compartment and the Golgi, with those formed from the Golgi being longer in LPP3-silenced cells than in control cells; (ii) impairs the Rab6-dependent retrograde transport of Shiga toxin subunit B from the Golgi to the ER, but not the anterograde transport of VSV-G or ssDsRed; and (iii) induces a high accumulation of Golgi-associated membrane buds. LPP3 depletion also reduces levels of de novo synthesized DAG and the Golgi-associated DAG contents. Remarkably, overexpression of a catalytically inactive form of LPP3 mimics the effects of LPP3 knockdown on Rab6-dependent retrograde transport. We conclude that LPP3 participates in the formation of retrograde transport carriers at the ER-Golgi interface, where it transitorily cycles, and during its route to the plasma membrane.
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Seventy-five percent of breast cancers are estrogen receptor α positive (ER(+)). Research on these tumors is hampered by lack of adequate invivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER(+) tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow invivo. Grafting into the milk ducts suppresses SLUG; ER(+) tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER(+) PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.
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Digitoitu 1. 8. 2008.
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Digitoitu 16. 7. 2008.
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Digitoitu 16. 7. 2008.
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Digitoitu 17. 7. 2008.
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The dissertation I knit, therefore I am! Learning and identity in informal space has two main purposes. The first purpose being an investigation of how new value attributions and thinking can generate novel and usable knowledge to the field of craftsmanship, and the second purpose being a display of a different and overlooked philosophical and cultural potential in a reflexive mode of expression, which is able to reflect the normative comprehension of craftsmanship. The dissertation focuses on learning and identity in informal spaces of learning and how it is possible to relate such a learning perspective to crafts training in educational establishments. The empirical foundation of this dissertation is craftivism. In the dissertation activists from the Nordic countries have been interviewed about what they do when they put up their textile graffiti on lamp posts and house walls. Three research problems are presented: 1) What stories do people who work as crafts activists, tell about ways of relating and methods of action when they make crafts? 2) What do these stories tell about learning and identity? 3) How may the research results influence training and education in craftsmanship? These questions are being asked in order to acquire new knowledge in two aspects; first aspect being knowledge about crafts in relation to techniques, tradition and the objects in crafts, and the second aspect being knowledge about learning and identity in informal spaces of learning. The dissertations theoretical foundation is post structural and sociocultural combined with hermeneutical-inspired qualitative interviews. The authors position and pre-understanding is subject to discussion in relation to the informant; the performing activist, as the background for both of them is craftsmanship. Starting from cultural studies, it is possible to see the activist subjects conditions of possibilities in the culture, as the activism of the sub-cultural phenomenons craft lights up through a performing approach to the individuals actions. First the research material has been analysed for events of textile graffiti and possible themes in the events, after which the results have been summarised. Next the research material has been analysed for events about learning and identity due to the authors wish of comprehending the background of and motivational force in activism. The analysis is divided in main perspectives with different dimensions. The results of the analysis show the activist subjects construction of an individual who actively takes part in a community by e.g. creating joy, changing the worlds perception of sustainability or by feminizing the public space. By taking crafts over the borders (and away from the class room) crafts become contextualized in a novel fashion thus obtaining an independent status. In this fashion the dissertation writes itself into a new method of comprehending and performing traditional craftsmanship techniques.
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Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.
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Comprenant les vingt-quatre traits de pit filiale avec gravures (livre 1), des exemples d'intelligence prcoce (livre 2), de bonne ducation domestique (livre 3), de perfectionnement de soi-mme (livre 4), de fidlit et de dvouement (livre 5).
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Les estrognes jouent un rle primordial dans le dveloppement et le fonctionnement des tissus reproducteurs par leurs interactions avec les rcepteurs des estrognes ER et ER. Ces rcepteurs nuclaires agissent comme facteurs de transcription et contrlent lexpression des gnes de faon hormono-dpendante et indpendante grce leurs deux domaines dactivation (AF-1 et AF-2). Une drgulation de leur activit transcriptionnelle est souvent lorigine de pathologies telles que le cancer du sein, de lendomtre et des ovaires. Alors que ER est utilis comme facteur pronostic pour lutilisation dagents thrapeutiques, limportance de la valeur clinique de ER est encore controverse. Toutefois, des vidences rcentes lui associent un pouvoir anti-tumorignique en dmontrant que sa prsence favorise linhibition de la progression de ces cancers ainsi que lefficacit des traitements. En combinaisons avec dautres tudes, ces observations dmontrent que bien que les deux isoformes partagent une certaine similitude daction, les ERs sont en mesure dexercer des fonctions distinctes. Ces diffrences sont fortement attribuables au faible degr dhomologie observ entre certains domaines structuraux des ERs, comme le domaine AF-1, ce qui fait en sorte que les diffrents sites de modifications post-traductionnelles (MPTs) prsents sur les ERs sont trs peu conservs entre les isoformes. Or, lactivit transcriptionnelle ligand-dpendante et indpendante des ERs est hautement rgule par les MPTs. Elles sont impliques tous les niveaux de lactivation des ERs incluant la liaison et la sensibilit au ligand, la localisation cellulaire, la dimrisation, linteraction avec lADN, le recrutement de corgulateurs transcriptionnels, la stabilit et larrt de la transcription. Ainsi, de par leur dissimilitude, les ERs seront diffremment rguls par la signalisation cellulaire. Comme un dbalancement de plusieurs voies de signalisation ont t associes la progression de tumeurs ER-positives ainsi quau dveloppement dune rsistance, une meilleure comprhension de limpact des MPTs sur la rgulation spcifique des ERs savre essentielle en vue de proposer et/ou dvelopper des traitements adquats pour les cancers gyncologiques. Les rsultats prsents dans cette thse ont pour objectif de mieux comprendre les rles des MPTs sur lactivit transcriptionnelle de ER qui sont, contrairement ER, trs peu connus. Nous dmontrons une rgulation dynamique de ER par la phosphorylation, lubiquitination et la sumoylation. De plus, toutes les MPTs nouvellement dcouvertes par mes recherches se situent dans lAF-1 de ER et permettent de mieux comprendre le rle capital jou par ce domaine dans la rgulation de lactivit ligand-dpendante et indpendante du rcepteur. Dans la premire tude, nous observons quen rponse aux MAPK, lAF-1 de ER est phosphoryl au niveau de srines spcifiques et quelles jouent un rle important dans la rgulation de lactivit ligand-indpendante de ER par la voie ubiquitine-protasome. En effet, la phosphorylation de ces srines rgule le cycle dactivation-dgradation de ER en modulant son ubiquitination, sa mobilit nuclaire et sa stabilit en favorisant le recrutement de lubiquitine ligase E6-AP. De plus, ce mcanisme daction semble tre derrire la rgulation diffrentielle de lactivit de ER et ER observe lors de linhibition du protasome. Dans le second papier, nous dmontrons que lactivit et la stabilit de ER en prsence destrogne sont troitement rgules par la sumoylation phosphorylation-dpendante de lAF-1, processus hautement favoris par laction de la kinase GSK-3. La sumoylation de ER par SUMO-1 prvient la dgradation du rcepteur en entrant en comptition avec lubiquitination au niveau du mme site accepteur. De plus, contrairement ER, SUMO-1 rprime lactivit de ER en altrant son interaction avec lADN et lexpression de ses gnes cibles dans les cellules de cancers du sein. galement, ces recherches ont permis didentifier un motif de sumoylation dpendant de la phosphorylation (pSuM) jusqu lors inconnu de la communaut scientifique, offrant ainsi un outil supplmentaire la prdiction de nouveau substrat de la sumoylation. En plus de permettre une meilleure comprhension du rle des signaux intracellulaires dans la rgulation de lactivit transcriptionnelle de ER, nos rsultats soulignent limportance des MPTs dans linduction des diffrences fonctionnelles observes entre ER et ER et apportent des pistes supplmentaires la comprhension de leurs rles physiopathologiques respectifs.
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Microwave dielectric ceramics based on RETiTaO6 (RE = La, Cc, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Y, Er, Yb, Al, and In) were prepared using a conventional solid-state ceramic route. The structure and microstructure of the samples were analyzed using x-ray diffraction and scanning electron microscopy techniques. The sintered samples were characterized in the microwave frequency region. The ceramics based on Ce, Pr, Nd, Sm, Eu, Gd, Tb, and Dy, which crystallize in orthorhombic aeschynite structure, had a relatively high dielectric constant and positive T f while those based on Ho, Er, and Yb, with orthorhombic euxenite structure, had a low dielectric constant and negative Tf. The RETiTaO6 ceramics had a high-quality factor. The dielectric constant and unit cell volume of the ceramics increased with an increase in ionic radius of the rare-earth ions, but density decreased with it. The value of Tf increased with an increase in RE ionic radii, and a change in the sign of Tf occurred when the ionic radius was between 0.90 and 0.92 A. The results indicated that the boundary of the aeschynite to euxenite morphotropic phase change lay between DyTiTaO6 and HoTiTaO6. Low-loss ceramics like ErTiTaO6 (Er = 20.6, Qxf = 85,500), EuTiTaO6 (Er = 41.3, Qxf = 59,500), and YTiTaO6 (Er = 22.1, Qxf = 51,400) are potential candidates for dielectric resonator applications
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