Search

In plants, local adaptation across species range is frequent. Yet, much has to be discovered on its environmental drivers, the underlying functional traits and their molecular determinants. Genome scans are popular to uncover outlier loci potentially involved in the genetic architecture of local adaptation, however links between outliers and phenotypic variation are rarely addressed. Here we focused on adaptation of teosinte populations along two elevation gradients in Mexico that display continuous environmental changes at a short geographical scale. We used two common gardens, and phenotyped 18 traits in 1664 plants from 11 populations of annual teosintes. In parallel, we genotyped these plants for 38 microsatellite markers as well as for 171 outlier single nucleotide polymorphisms (SNPs) that displayed excess of allele differentiation between pairs of lowland and highland populations and/or correlation with environmental variables. Our results revealed that phenotypic differentiation at 10 out of the 18 traits was driven by local selection. Trait covariation along the elevation gradient indicated that adaptation to altitude results from the assembly of multiple co-adapted traits into a complex syndrome: as elevation increases, plants flower earlier, produce less tillers, display lower stomata density and carry larger, longer and heavier grains. The proportion of outlier SNPs associating with phenotypic variation, however, largely depended on whether we considered a neutral structure with 5 genetic groups (73.7%) or 11 populations (13.5%), indicating that population stratification greatly affected our results. Finally, chromosomal inversions were enriched for both SNPs whose allele frequencies shifted along elevation as well as phenotypically-associated SNPs. Altogether, our results are consistent with the establishment of an altitudinal syndrome promoted by local selective forces in teosinte populations in spite of detectable gene flow. Because elevation mimics climate change through space, SNPs that we found underlying phenotypic variation at adaptive traits may be relevant for future maize breeding.

[This corrects the article DOI: 10.1371/journal.pone.0179988.].

BACKGROUND:Clinical and echocardiography follow-up is recommended in patients with aortic stenosis to detect symptom onset, thus a watchful waiting approach has to be safe and effective. For both AS patients and their general practitioners, evaluation of valvular heart disease (VHD) knowledge, after the indexed specialized assessment has never been measured. AIMS:To evaluate the knowledge of clinical symptoms of aortic stenosis by both patients and their general practitioner. METHODS:Sixty-four patients, with moderate to severe and initially asymptomatic AS (median AVA (interquartile range) 1.01(0.80-1.15) cm2) previously referred to a tertiary center and medically managed for at least 6 months after the index echocardiogram, and their primary care doctors were interviewed on the phone and asked to answer specific questions related to knowledge of aortic stenosis symptoms. RESULTS:Fifty-six percent of patients quoted shortness of breath as one of the aortic stenosis symptoms, and only 16% knew the 3 aortic stenosis symptoms. Fifty percent of patients reported having received sufficient information regarding aortic stenosis; only 48% remembered receiving information regarding specific symptoms. Only 14% general practitioners quoted the 3 specific symptoms. According to the initial recommendation, only 41 patients (64%) benefitted from a 6-to-12 month clinical and echocardiography follow up. CONCLUSION:GPs are not sufficiently trained to safely manage AS patients in the community and to ensure adequate follow-up and monitoring. AS patients were not properly informed about their diagnosis and symptomatology. Hence, therapeutic education should be improved for patients with asymptomatic AS and continuous medical education on VHD should be reinforced, for GPs.

11β-Hydroxysteroid dehydrogenases (11beta-HSD) modulate mineralocorticoid receptor transactivation by glucocorticoids and regulate access to the glucocorticoid receptor. The isozyme 11beta-HSD2 is selectively expressed in mineralocorticoid target tissues and its activity is reduced in various disease states with abnormal sodium retention and hypertension, including the apparent mineralocorticoid excess. As 50% of patients with essential hypertension are insulin resistant and hyperinsulinemic, we hypothesized that insulin downregulates the 11beta-HSD2 activity. In the present study we show that insulin reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT-29) at the transcriptional level, in a time and dose dependent manner. The downregulation was reversible and required new protein synthesis. Pathway analysis using mRNA profiling revealed that insulin treatment modified the expression of the transcription factor family C/EBPs (CCAAT/enhancer-binding proteins) but also of glycolysis related enzymes. Western blot and real time PCR confirmed an upregulation of C/EBP beta isoforms (LAP and LIP) with a more pronounced increase in the inhibitory isoform LIP. EMSA and reporter gene assays demonstrated the role of C/EBP beta isoforms in HSD11B2 gene expression regulation. In addition, secretion of lactate, a byproduct of glycolysis, was shown to mediate insulin-dependent HSD11B2 downregulation. In summary, we demonstrate that insulin downregulates HSD11B2 through increased LIP expression and augmented lactate secretion. Such mechanisms are of interest and potential significance for sodium reabsorption in the colon.