Adaptation of a quantitative trait to a changing environment: New analytical insights on the asexual and infinitesimal sexual models.

Predicting the adaptation of populations to a changing environment is crucial to assess the impact of human activities on biodiversity. Many theoretical studies have tackled this issue by modeling the evolution of quantitative traits subject to stabilizing selection around an optimal phenotype, whose value is shifted continuously through time. In this context, the population fate results from the equilibrium distribution of the trait, relative to the moving optimum. Such a distribution may vary with the shape of selection, the system of reproduction, the number of loci, the mutation kernel or their interactions. Here, we develop a methodology that provides quantitative measures of population maladaptation and potential of survival directly from the entire profile of the phenotypic distribution, without any a priori on its shape. We investigate two different systems of reproduction (asexual and infinitesimal sexual models of inheritance), with various forms of selection. In particular, we recover that fitness functions such that selection weakens away from the optimum lead to evolutionary tipping points, with an abrupt collapse of the population when the speed of environmental change is too high. Our unified framework allows deciphering the mechanisms that lead to this phenomenon. More generally, it allows discussing similarities and discrepancies between the two systems of reproduction, which are ultimately explained by different constraints on the evolution of the phenotypic variance. We demonstrate that the mean fitness in the population crucially depends on the shape of the selection function in the infinitesimal sexual model, in contrast with the asexual model. In the asexual model, we also investigate the effect of the mutation kernel and we show that kernels with higher kurtosis tend to reduce maladaptation and improve fitness, especially in fast changing environments.

Increased circulating concentrations of bioactive PTH 1-84 in patients with heart failure.

BACKGROUND: PTH is related to left ventricular hypertrophy and its circulating levels are associated with worse prognosis in patients with heart failure (HF). The objectives of our study were to measure the circulating levels of bioactive PTH 1-84 through third-generation assay in HF patients, to determine their association with the disease severity as well as their relation with recognized biomarkers of HF worsening and prognosis. METHODS: PTH 1-84 concentrations were determined in 76 HF patients and in 49 healthy volunteers. Circulating levels of amino-terminal proatrial natriuretic peptide (Nt-proANP), B-type natriuretic peptide (BNP), Nt-proBNP, proBNP, and big endothelin-1 (Big ET-1) were also measured. RESULTS: HF patients had in- creased PTH 1-84 levels in comparison to controls. A significant increase of the PTH 1-84 circulating concentrations was observed according to the New York Heart Association functional classes. PTH 1-84 circulating concentrations were also significantly correlated with Nt-proANP, BNP, Nt-proBNP, proBNP, and Big ET-1. CONCLUSIONS: PTH 1-84 circulating levels are significantly increased in HF patients in comparison to healthy individuals. Our study has also demonstrated that circulating concentrations of bioactive PTH are related to HF severity and well-established biomarkers of the worsening of the disease.

Comparison between intact and bioactive parathyroid hormone assays in patients with severe heart failure.

OBJECTIVES: Parathyroid hormone (PTH) is a major systemic calcium-regulating hormone. Recent evidence has suggested that measurement of PTH might provide complementary information for the diagnosis and risk stratification of patients with heart failure (HF). The aim of our study was to compare intact and bioactive PTH assays in patients with severe heart failure. DESIGN AND METHODS: The following measurements were carried out in blood samples from 73 patients with severe heart failure: bioactive PTH (1-84) assay, intact PTH assay, non-PTH (1-84), 25-hydroxyvitamin D, B-type natriuretic peptide (BNP), N-terminal proBNP (Nt-proBNP), Galectin-3 and high sensitive troponin T (hsTnT). RESULTS: The correlation between intact and bioactive PTH assays was very high in HF patients. However, the bioactive PTH concentrations were lower than those measured with the intact assay. Intact and bioactive PTH as well as non-PTH (1-84) was significantly and positively correlated to BNP, Nt-proBNP, and galectin-3 but not to hsTnT. The strongest relationships with these cardiac biomarkers and with cardiovascular death were observed with the bioactive PTH assay. CONCLUSIONS: The PTH concentrations obtained with intact and bioactive assays are not comparable in patients with severe HF. The specificity of PTH assays might therefore impact on the potential diagnosis and prognosis values of PTH testing in patients with heart failure.