RESUMO
OBJECTIVE: More is known about the experience of occupational therapists than the experience of patients during the profession's early years. We examined soldiers' experiences of occupational therapy in American Base Hospital 9 in France during World War I through analysis of a 53-line poem by Corporal Frank Wren contained in the unpublished memoir of occupational therapy reconstruction aide Lena Hitchcock. METHOD: Historical documentary research methods and thematic analysis were used to analyze the poem, the memoir, and the hospital's published history. RESULTS: The poem describes the activities engaged in during occupational therapy, equipment used, and the context of therapy. It articulates positive dimensions of the experience of engaging in activities, including emotional benefits, diversion, and orthopedic benefits. CONCLUSION: Previous historical research has identified core philosophical premises about the use of occupational therapy; in this article, the enactment of these principles is established through the analysis of a soldier's account of receiving occupational therapy.
Assuntos
Hospitais Militares/história , Militares/história , Narração , Terapia Ocupacional/história , I Guerra Mundial , História do Século XX , Humanos , Poesia como AssuntoRESUMO
Mycotoxin induced hepatoxocity has been linked to oxidative stress, resulting from either an increase in levels of reactive oxygen species (ROS) above normal levels and/or the suppression of antioxidant protective pathways. However, few detailed molecular studies of mycotoxicoses in animals have been carried out. This study use current RNA-seq based approaches to investigate the effects of mycotoxin exposure in a ruminant model. Having first assembled a de novo reference transcriptome, we use RNA-Seq technology to define in vivo hepatic gene expression changes resulting from mycotoxin exposure in relationship to pathological effect. As expected, characteristic oxidative stress related gene expression is markedly different in animals exhibiting poorer outcomes. However, expression of multiple genes critical for detoxification, particularly members of the cytochrome P450 gene family, was significantly higher in animals exhibiting mycotoxin tolerance ('resistance'). Further, we present novel evidence for the amplification of Wnt signalling pathway activity in 'resistant' animals, resulting from the marked suppression of multiple key Wnt inhibitor genes. Notably, 'resistance' may be determined primarily by the ability of an individual to detoxify secondary metabolites generated by the metabolism of mycotoxins and the potentiation of Wnt signalling may be pivotal to achieving a favourable outcome upon challenge.
Assuntos
Micotoxicose/veterinária , Micotoxinas/toxicidade , Doenças dos Ovinos/metabolismo , Animais , Resistência à Doença , Ontologia Genética , Inativação Metabólica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Micotoxicose/genética , Micotoxicose/metabolismo , Micotoxinas/metabolismo , Análise de Sequência de RNA , Ovinos , Doenças dos Ovinos/genética , Carneiro Doméstico , Transcriptoma , Via de Sinalização WntRESUMO
A highly conserved defence mechanism has evolved to protect cells from oxidative stress and xenobiotic exposure. A network of coupled xenobiotic metabolizing enzymatic reactions (XMEs) converts free oxidative radicals to less damaging metabolites, while efflux pumps remove toxins and XME derivatives from the cell. These mechanisms have been well studied in the contexts of hypoxia and Multidrug Resistance (MDR). Exposure of ruminants to fungal toxins leads to hepatotoxicosis and subsequent skin eczema (FE) depending upon toxic burden. Using toxin challenge in sheep we have investigated the potential for epigenetic regulation in cellular responses to xenobiotic exposure with a focus on the efflux protein ABCG2 which functions in Phase III of the defence mechanism. We show that 'resistance' to FE disease is positively associated with ABCG2 expression, and inversely correlated with DNA methylation state at CpG sites in the regulatory region of the ABCG2 gene. The analytical sensitivity provided by the Sequenom EpiTyper MS platform allows resolution of individual CpG sites varying significantly with disease progression, informing fine mapping of relevant transcription factor bindings which underpin this epigenetic response. Our findings indicate that epigenetic mechanisms are important to xenobiotic responses, suggest useful diagnostic markers and raise potential opportunities for disease remediation. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Epigênese Genética/genética , Regulação da Expressão Gênica/genética , Espectrometria de Massas/métodos , Micotoxinas/toxicidade , Análise de Sequência de DNA/métodos , Xenobióticos/toxicidade , Animais , Sequência de Bases , DNA/genética , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Exposição Ambiental/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Dados de Sequência Molecular , OvinosRESUMO
The p53 tumor suppressor plays a major role in preventing tumor development by transactivating genes to remove or repair potentially tumorigenic cells. Here we show that the Y-box-binding protein, YB1, acts as a negative regulator of p53. Using reporter assays we show that YB1 represses transcription of the p53 promoter in a sequence-specific manner. We also show that YB1 reduces endogenous levels of p53, which in turn reduces p53 activity. Conversely, inhibiting YB1 in a variety of tumor cell lines induces p53 activity, resulting in significant apoptosis via a p53-dependent pathway. These data suggest that YB1 may, in some situations, protect cells from p53-mediated apoptosis, indicating that YB1 may be a good target for the development of new therapeutics.
