Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that metabolic risk markers arise when vulnerable individuals are exposed to social challenges later in life.
Summary Loss of heterozygosity (LOH) in loci of the 15q15.1, 12p13, 1p32, 17q21 and 13q12-13 regions may collaborate in the inactivatio n of RAD51, RAD52, RAD54, BRCA1, BRCA2 and possibly other genes implicated in the repair of double-stranded DNA and in DNA recombination. We investigate allelic losses in microsatellites of the RAD51, RAD52, RAD54, BRCA1 and BRCA2 regions, and their correlations with nine pathologic parameters in 127 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using 15 markers of the 15q15.1, 12p13.3, 1p32, 17q21 and 13q12-13 regions. LOH was found in the RAD51 region in 32% of tumours, in t he RAD52 region in 16%, in RAD54 in 20% and in the BRCA1 and BRCA2 regions in 49% and 44% respectivel y. Significant correlations between one or more regions with concomitant LOH and pathologic parameters were observed with respect to age (P = 0.008), oestrogen receptor content (P = 0.03), progesterone receptors (P = 0.003), higher grade (P = 0.001), more advanced stage (P = 0.004) and peritumoural vessel involvement (P < 0.0001). The number of cases in which LOH was observed simultaneously in two or more regions was always higher than expected on the basis of their statistical probabilit y, and curiousl y, the three patients with LOH at five regions concomi tantly were under the age of 30 years. These results suggest that LOH at these regions could be related to breast cance r, and probably to a poo r tumour prognosis .
Boreal woodland caribou (Rangifer tarandus caribou) are designated as threatened under Canada’s Species at Risk Act. A Recovery Strategy for the boreal population of caribou identified critical habitat for all but 1 of 51 caribou ranges – Saskatchewan’s Boreal Shield (SK1). The strategy identified 65% undisturbed habitat as the threshold below which a local population was not likely to be self-sustaining. Disturbance was measured as the combined effects of fires <40 years and anthropogenic land use. The fire component of the total disturbance model used fire polygons that were delineated using traditional mapping methods. Our study maps fire from 1988–2013 using the differenced Normalized Burn Ratio analysis of Landsat Thematic mapper and Operational Land Imager. Annual burned areas based on fire perimeters were similar between traditionally and Landsat-derived inventory approaches, but the traditional methods overestimated within-burn areas by 31.8%, as a result of including post-fire residuals and water bodies as burned. The federal recovery model assumes that all lands within provincial fire polygons (<40 years) are inadequate as caribou habitat, and ignores the potential value of post-fire residuals and water bodies as habitat. For some Boreal Shield ranges including SKI, where fire comprises the majority of the total disturbance and residual patches are abundant, total disturbance calculations, critical habitat designation and range planning decisions should take into account residuals, including water bodies.
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