982 resultados para ANC-AP


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Includes index.

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Trägerband: 'E. lin. 4. N. 5'; Vorbesitzer: Karmeliterkloster Frankfurt am Main

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Vorbesitzer: Dominikanerkloster Frankfurt am Main

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The AP-2 transcription factor family is presumed to play an important role in the regulation of the keratinocyte squamous differentiation program; however, limited functional data are available to support this. In the present study, the activity and regulation of AP-2 were examined in differentiating human epidermal keratinocytes. We report that (1) AP-2 transcriptional activity decreases in differentiated keratinocytes but remains unchanged in differentiation-insensitive squamous cell carcinoma cell lines, (2) diminished AP-2 transcriptional activity is associated with a loss of specific DNA-bound AP-2 complexes, and (3) there is an increase in the ability of cytoplasmic extracts, derived from differentiated keratinocytes, to phosphorylate AP-2alpha and AP-2beta when cells differentiate. In contrast, extracts from differentiation-insensitive squamous cell carcinoma cells are unable to phosphorylate AP-2 proteins. Finally, the phosphorylation of recombinant AP-2alpha by cytosolic extracts from differentiated keratinocytes is associated with decreased AP-2 DNA-binding activity. Combined, these data indicate that AP-2 trans-activation and DNA-binding activity decrease as keratinocytes differentiate, and that this decreased activity is associated with an enhanced ability to phosphorylate AP-2alpha and beta.

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Fetal epithelium retains the ability to re-epithelialize a wound in organotypic culture in a manner not dependent on the presence of underlying dermal substrata. This capacity is lost late in the third trimester of gestation or after embryonic day 17 (E-17) in the rat such that embryonic day 19 (E-19) wounds do not re-epithelialize. Moreover, wounds created in E-17 fetuses in utero heal in a regenerative, scar-free fashion. To investigate the molecular events regulating re-epithelialization in fetal skin, the wound-induced expression profile and tissue localization of activator protein 1 (AP-1) transcription factors c-Fos and c-Jun was characterised in E-17 and E-19 skin using organotypic fetal cultures. The involvement of mitogen-activated protein kinase (MAPK) signaling in mediating wound-induced transcription factor expression and wound re-epithelialization was assessed, with the effect of wounding on the expression of keratinocyte differentiation markers determined. Our results show that expression of AP-1 transcription factors was induced immediately by wounding and localized predominantly to the epidermis in E-17 and E-19 skin. c-fos and c-jun induction was transient in E-17 skin with MAPK-dependent c-fos expression necessary for the re-epithelialization of an excisional wound in organotypic culture. In E-19 skin, AP-11 expression persisted beyond 12 h post-wounding, and marked upregulation of the keratinocyte differentiation markers keratin 10 and loricrin was observed. No such changes in the expression of keratin 10 or loricrin occurred in E-17 skin. These findings indicate that re-epithelialization in fetal skin is regulated by wound-induced AP-1 transcription factor expression via MAPK and the differentiation status of keratinocytes.

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Esta dissertação investiga a narrativa de visão apocalíptica encontrada em Ap 13,1-18. Ela parte da pergunta sobre a realidade que influenciou o autor no momento da composição, utilizando-se, assim, de uma linguagem provocativa. Nossa hipótese indica que o Apocalipse de João, importante fonte das experiências do Cristianismo primitivo no final do primeiro século, proporciona uma dura crítica às exigências de adoração dirigidas às autoridades romanas através do Culto Imperial. As imagens das bestas descritas em Ap 13,1-18 expressam este tema através de uma linguagem provocativa, fundamentada na força da palavra e na tradição do mito do antagonista encontrado no Antigo Oriente Próximo. Neste sentido, acreditamos que o autor demoniza e estigmatiza as expressões da religião oficial, as quais tratam os governantes como seres divinos, e os promotores do Culto Imperial na região da Ásia Menor.(AU)

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O objetivo central deste trabalho é efetuar uma análise comparativa da contabilização dos ativos intangíveis no âmbito do SNC e do SNC-AP. A convergência de ambos os normativos nos critérios de reconhecimento e mensuração não é plena. No que respeita ao reconhecimento, é dada a possibilidade, no âmbito público, de um elemento ser reconhecido como ativo, mesmo que não produza benefícios económicos futuros para a entidade, desde que possua potencial de serviço. No que à mensuração se refere, na norma aplicada ao setor público o modelo da revalorização é visto como uma alternativa ao modelo do custo, não estando previsto nesse modelo o reconhecimento de perdas por imparidade. As conclusões observadas neste trabalho poderão contribuir para que outros estudos se desenvolvam no âmbito de uma análise conjunta aos normativos contabilísticos adotados em Portugal.

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Perante a atual reforma da Contabilidade Pública em Portugal, foi aprovado, em setembro de 2015, o novo Sistema de Normalização Contabilística para as Administrações Públicas (SNC-AP). Este trabalho tem por objetivos analisar o definido no POCAL e no SNC-AP quanto ao reconhecimento e à mensuração dos ativos fixos tangíveis (AFT). Este estudo permite concluir que o novo normativo evidencia um avanço face ao POCAL, definindo não só o conceito de ativo e de AFT, como também os critérios de reconhecimento que um elemento deve cumprir para que possa ser reconhecido como tal, permitindo assim uma maior consistência no reconhecimento destes elementos, por parte das diferentes entidades públicas. Por outro lado, no que respeita à mensuração, o SNC-AP segue de perto, com as devidas adaptações, os normativos internacionais, introduzindo dois momentos de mensuração dos AFT, e referindo o justo valor explicitamente enquanto critério de mensuração aplicável a situações concretas.

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We have previously tested the effects of high dose AA supplements on human volunteers in terms of reducing DNA damage, as a possible mechanism of the vitamin’s proposed protective effect against cancer and detected a transient, pro-oxidant effect at high doses (500 mg/day). Herein, we present evidence of a pro-oxidant effect of the vitamin when added to CCRF cells at extracellular concentrations which mimic those present in human serum in vivo (50–150AM). The activation of the transcription factor AP-1 was optimal at 100 AM AA following 3h exposure at 37jC. A minimum dose of 50 AM of AA activated NFnB but there appeared to be no dose-dependent effect. Increases of 2–3 fold were observed for both transcription factors when cells were exposed to 100 AM AA for 3h, comparing well with the pro-oxidant effect of H2O2 at similar concentrations. In parallel experiments the activation of AP-1 (binding to DNA) was potentiated when cells were pre-incubated with AA prior to exposure with H2O2. Cycloheximide pretreatment (10 Ag/ml for 15min) caused a 50% inhibition of AP-1 binding to DNA suggesting that it was due to a combination of increasing the binding of pre-existing Fos and Jun and an increase in their de novo synthesis. Cellular localisation was confirmed by immunocytochemistry using antibodies specific for c-Fos and c-Jun proteins. These results suggest that extracellular AA can elicit an intracellular stress response resulting in the activation of the oxidative stress-responsive transcription factors AP-1 and NFnB. These transcription factors are involved in the induction of genes associated with an oxidative stress response, cell cycle arrest and DNA repair confirmed by our cDNA microarray analysis (Affymetrix). This may explain the abilty for AA to appear to inhibit 8-oxodG, yet simultaneously generate another oxidative stress biomarker, 8-oxo-dA. These results suggest a completely novel DNA repair action for AA. Whether this action is relevant to our in vivo findings will be the subject of our future research.

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Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.