3 resultados para COPY NUMBER CHANGES

em Universidad de Alicante


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Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout) and gain-of-function (transgenic overexpression) mouse models of GCAP2. Rod synaptic ribbons in GCAPs−/− mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs−/− background (GCAP2 expression in the absence of endogenous GCAP1) had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of synaptic ribbons.

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Background: Migrant workers have been one of the groups most affected by the economic crisis. This study evaluates the influence of changes in employment conditions on the incidence of poor mental health of immigrant workers in Spain, after a period of 3 years, in context of economic crisis. Methods: Follow-up survey was conducted at two time points, 2008 and 2011, with a reference population of 318 workers from Colombia, Ecuador, Morocco and Romania residing in Spain. Individuals from this population who reported good mental health in the 2008 survey (n = 214) were interviewed again in 2011 to evaluate their mental health status and the effects of their different employment situations since 2008 by calculating crude and adjusted odds ratios (aORs) for sociodemographic and employment characteristics. Findings: There was an increased risk of poor mental health in workers who lost their jobs (aOR = 3.62, 95%CI: 1.64–7.96), whose number of working hours increased (aOR = 2.35, 95%CI: 1.02–5.44), whose monthly income decreased (aOR = 2.75, 95%CI: 1.08–7.00) or who remained within the low-income bracket. This was also the case for people whose legal status (permission for working and residing in Spain) was temporary or permanent compared with those with Spanish nationality (aOR = 3.32, 95%CI: 1.15–9.58) or illegal (aOR = 17.34, 95%CI: 1.96–153.23). In contrast, a decreased risk was observed among those who attained their registration under Spanish Social Security system (aOR = 0.10, 95%CI: 0.02–0.48). Conclusion: There was an increase in poor mental health among immigrant workers who experienced deterioration in their employment conditions, probably influenced by the economic crisis.

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We have used X-ray photoelectron spectroscopy (XPS) as a novel method to investigate the causes of colour changes in a reddish limestone under irradiation by a Q-switched Nd:YAG 1064 nm laser. We irradiated clean dry and wet surfaces of Pidramuelle Roja, a building stone frequently used in the Asturian heritage, at fluences ranging from 0.12 to 1.47 J cm−2. We measured the colour coordinates and undertook XPS analysis of the state of oxidation of iron both before and after irradiation. Visible colour changes and potential aesthetic damage occurred on dry surfaces from a fluence of 0.31 J cm−2, with the stone showing a greening effect and very intense darkening. The colour change on dry surfaces was considerably higher than on wet surfaces, which at the highest fluence (1.47 J cm−2) was also above the human visual detection threshold. The use of XPS demonstrated that the change in colour (chroma and hue) is associated with a reduction in the iron oxidation state on dry surfaces during laser irradiation. This points out to a potential routinary use of XPS to analyse causes of colour changes during laser cleaning in other types of coloured building stones.