Identidade do homem resiliente no contexto de adoecer por câncer de próstata: uma perspectiva cultural / Identity of the resilient man in the context of ill with prostate cancer: a cultural perspective / Identidad del hombre resiliente en el contexto al enfermar por cáncer de próstata: una perspectiva cultural

O estudo objetivou conhecer o contexto do homem resiliente ao adoecer por câncer de próstata. Trata-se de um estudo de caso etnográfico realizado com dois homens sobreviventes ao câncer de próstata, com alto grau de resiliência. Os dados foram coletados no domicílio, no período de abril e maio de 2012, por meio da entrevista semiestruturada em profundidade, de observação participante e do ecomapa. Pela análise dos dados construíram-se duas unidades de sentido: "Identidade do homem resiliente: contextualizando os informantes" e "O homem resiliente descobrindo-se doente". Apreende-se que a identidade de ser homem resiliente, para estes informantes, foi marcada pela diferença histórica e cultural que permeou as suas ações, no processo de adoecimento por câncer de próstata. Considera-se importante que os enfermeiros atentem para os aspectos culturais da saúde do homem, para que este possa sentir-se parte integrante do processo de cura, tornando-se sujeito ativo frente à própria saúde.

The study aimed to understand the context of resilient man when ill with prostate cancer. This is an ethnographic case study conducted with two prostate cancer survival men with a high degree of resilience. The data was collected on their places, in 2012 April and May, using semi-structured in-depth interviews, participant observation and ecomap. For the data analysis, it was built two units of meaning: "Identity of the resilient man: contextualizing the informants" and "The resilient man finding himself ill". It was noticed that the identity of being a resilient man, to these informants, was marked by historical and cultural difference which permeated their actions in the process of being ill with prostate cancer. It is important that nurses pay attention to the cultural aspects of human health, so that they can feel part of the healing process, becoming an active subject facing their own health.

El estudio enfocó conocer el contexto del hombre resiliente al enfermar por cáncer de próstata. Se trata de un estudio de caso etnográfico realizado con dos hombres sobrevivientes al cáncer de próstata con alto grado de resiliencia. Los datos fueron recogidos en el domicilio, en el período de abril y mayo de 2012, por medio de entrevista semiestructurada en profundidad, observación participante y ecomapa. Por el análisis de los datos, se construyeron dos unidades de sentido: "Identidad del hombre resiliente: contextualizando a los informantes" y "El hombre resiliente descubriéndose enfermo". Se comprende que la identidad de ser hombre resiliente, para estos informantes, fue marcada por la diferencia histórica y cultural que hicieron permeables sus acciones en el proceso de enfermar por cáncer de próstata. Se considera importante que los enfermeros estén atentos a los aspectos culturales de la salud del hombre, para que este se pueda sentir parte integrante del proceso de cura, tornándose sujeto activo frente a la propia salud.

[Identity of the resilient man in the context of ill with prostate cancer: a cultural perspective]. / Identidade do homem resiliente no contexto de adoecer por câncer de próstata: uma perspectiva cultural.

The study aimed to understand the context of resilient man when ill with prostate cancer. This is an ethnographic case study conducted with two prostate cancer survival men with a high degree of resilience. The data was collected on their places, in 2012 April and May, using semi-structured in-depth interviews, participant observation and ecomap. For the data analysis, it was built two units of meaning: "Identity of the resilient man: contextualizing the informants" and "The resilient man finding himself ill". It was noticed that the identity of being a resilient man, to these informants, was marked by historical and cultural difference which permeated their actions in the process of being ill with prostate cancer. It is important that nurses pay attention to the cultural aspects of human health, so that they can feel part of the healing process, becoming an active subject facing their own health.

The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii.

BACKGROUND: The interferon-inducible immunity-related GTPases (IRG proteins/p47 GTPases) are a distinctive family of GTPases that function as powerful cell-autonomous resistance factors. The IRG protein, Irga6 (IIGP1), participates in the disruption of the vacuolar membrane surrounding the intracellular parasite, Toxoplasma gondii, through which it communicates with its cellular hosts. Some aspects of the protein's behaviour have suggested a dynamin-like molecular mode of action, in that the energy released by GTP hydrolysis is transduced into mechanical work that results in deformation and ultimately rupture of the vacuolar membrane. RESULTS: Irga6 forms GTP-dependent oligomers in vitro and thereby activates hydrolysis of the GTP substrate. In this study we define the catalytic G-domain interface by mutagenesis and present a structural model, of how GTP hydrolysis is activated in Irga6 complexes, based on the substrate-twinning reaction mechanism of the signal recognition particle (SRP) and its receptor (SRα). In conformity with this model, we show that the bound nucleotide is part of the catalytic interface and that the 3'hydroxyl of the GTP ribose bound to each subunit is essential for trans-activation of hydrolysis of the GTP bound to the other subunit. We show that both positive and negative regulatory interactions between IRG proteins occur via the catalytic interface. Furthermore, mutations that disrupt the catalytic interface also prevent Irga6 from accumulating on the parasitophorous vacuole membrane of T. gondii, showing that GTP-dependent Irga6 activation is an essential component of the resistance mechanism. CONCLUSIONS: The catalytic interface of Irga6 defined in the present experiments can probably be used as a paradigm for the nucleotide-dependent interactions of all members of the large family of IRG GTPases, both activating and regulatory. Understanding the activation mechanism of Irga6 will help to explain the mechanism by which IRG proteins exercise their resistance function. We find no support from sequence or G-domain structure for the idea that IRG proteins and the SRP GTPases have a common phylogenetic origin. It therefore seems probable, if surprising, that the substrate-assisted catalytic mechanism has been independently evolved in the two protein families.

Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii.

Members of the immunity-related GTPase (IRG) family are interferon-inducible resistance factors against a broad spectrum of intracellular pathogens including Toxoplasma gondii. The molecular mechanisms governing the function and regulation of the IRG resistance system are largely unknown. We find that IRG proteins function in a system of direct, nucleotide-dependent regulatory interactions between family members. After interferon induction but before infection, the three members of the GMS subfamily of IRG proteins, Irgm1, Irgm2 and Irgm3, which possess an atypical nucleotide-binding site, regulate the intracellular positioning of the conventional GKS subfamily members, Irga6 and Irgb6. Following infection, the normal accumulation of Irga6 protein at the parasitophorous vacuole membrane (PVM) is nucleotide dependent and also depends on the presence of all three GMS proteins. We present evidence that an essential role of the GMS proteins in this response is control of the nucleotide-bound state of the GKS proteins, preventing their GTP-dependent activation before infection. Accumulation of IRG proteins at the PVM has previously been shown to be associated with a block in pathogen replication: our results relate for the first time the enzymatic properties of IRG proteins to their role in pathogen resistance.

Mechanisms regulating the positioning of mouse p47 resistance GTPases LRG-47 and IIGP1 on cellular membranes: retargeting to plasma membrane induced by phagocytosis.

The recently identified p47 GTPases are one of the most effective cell-autonomous resistance systems known against intracellular pathogens in the mouse. One member of the family, LRG-47, has been shown to be essential for immune control in vivo of Listeria monocytogenes, Toxoplasma gondii, Mycobacterium tuberculosis, and Mycobacterium avium, possibly by promoting acidification of the phagosome. However, the intracellular localization of LRG-47, and the nature of its association with the phagosomal or any other membrane system is unknown. In this study, we show that LRG-47 is a Golgi-associated protein in the IFN-stimulated cell, which is rapidly recruited to active plasma membrane upon phagocytosis and remains associated with phagosomes as they mature. We show that the Golgi localization of LRG-47 is dependent on the integrity of an amphipathic helix near the C terminus, whereas the plasma membrane localization depends on an unidentified signal associated with the G domain. Unlike LRG-47, but like the published p47 resistance GTPase, IGTP, a further p47 GTPase, IIGP1, is associated with the endoplasmic reticulum. However, unlike IGTP, IIGP1 is associated with the endoplasmic reticulum by an N-terminal myristoylation modification. Thus, the p47 GTPases are a diverse battery of intracellular defense factors dynamically associated with different membrane systems.