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Prenatal stress (PS) has been related to altered hypothalamic-pituitary-adrenal (HPA) axis activity later in life. So far, studies in children assessing HPA axis functioning have focused on salivary cortisol, reflecting daytime activity. The present work is part of a prospective study and aims to extend knowledge about the association between PS and HPA axis regulation in children. To do so, we investigated cortisol, cortisone, and the ratio cortisone/(cortisone + cortisol) in the first morning urine of 45-month-old children in relation to several measures of maternal stress during pregnancy. Urinary cortisol and cortisone were measured by online turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry. PS was defined as: perceived stress for aim 1 (Perceived Stress Scale; n = 280); presence of self-reported (n = 371) and expert-rated psychopathology for aim 2 (Mini International Neuropsychiatric Interview; n = 281); continuous measures of anxiety and depression for exploratory aim 3 (State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale; n = 280). The ratio cortisone/(cortisone + cortisol) as a global marker for the balance between the enzymes metabolizing cortisol to cortisone and vice versa (11 beta-hydroxysteroid dehydrogenases type 1 and 2; 11 beta-HSD1 and 2) was not associated with any measure of maternal PS (aims 1-3). The present study provides insight into possible programming effects of PS on nocturnal HPA axis activity and a proxy of 11 beta-HSD in a large sample. The results suggest that the nocturnal rate of cortisol production is lower in children exposed to PS, but do not support the hypothesis of divergent 11 beta-HSD activity.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Context. Metal-poor massive stars are assumed to be progenitors of certain supernovae, gamma-ray bursts, and compact object mergers that might contribute to the early epochs of the Universe with their strong ionizing radiation. However, this assumption remains mainly theoretical because individual spectroscopic observations of such objects have rarely been carried out below the metallicity of the Small Magellanic Cloud. Aims. Here we explore the predictions of the state-of-the-art theories of stellar evolution combined with those of stellar atmospheres about a certain type of metal-poor (0.02 Z(circle dot)) hot massive stars, the chemically homogeneously evolving stars that we call Transparent Wind Ultraviolet INtense (TWUIN) stars. Methods. We computed synthetic spectra corresponding to a broad range in masses (20 130 M-circle dot) and covering several evolutionary phases from the zero-age main-sequence up to the core helium-burning stage. We investigated the influence of mass loss and wind clumping on spectral appearance and classified the spectra according to the Morgan-Keenan (MK) system. Results. We find that TWUIN stars show almost no emission lines during most of their core hydrogen-burning lifetimes. Most metal lines are completely absent, including nitrogen. During their core helium-burning stage, lines switch to emission, and even some metal lines (oxygen and carbon, but still almost no nitrogen) are detected. Mass loss and clumping play a significant role in line formation in later evolutionary phases, particularly during core helium-burning. Most of our spectra are classified as an early-O type giant or supergiant, and we find Wolf-Rayet stars of type WO in the core helium-burning phase. Conclusions. An extremely hot, early-O type star observed in a low-metallicity galaxy could be the result of chemically homogeneous evolution and might therefore be the progenitor of a long-duration gamma-ray burst or a type Ic supernova. TWUIN stars may play an important role in reionizing the Universe because they are hot without showing prominent emission lines during most of their lifetime.
Global change has complex eco-evolutionary consequences for organisms and ecosystems, but related concepts (e.g., novel ecosystems) do not cover their full range. Here we propose an umbrella concept of "ecological novelty" comprising (1) a site-specific and (2) an organism-centered, eco-evolutionary perspective. Under this umbrella, complementary options for studying and communicating effects of global change on organisms, ecosystems, and landscapes can be included in a toolbox. This allows researchers to address ecological novelty from different perspectives, e.g., by defining it based on (a) categorical or continuous measures, (b) reference conditions related to sites or organisms, and (c) types of human activities. We suggest striving for a descriptive, non-normative usage of the term "ecological novelty" in science. Normative evaluations and decisions about conservation policies or management are important, but require additional societal processes and engagement with multiple stakeholders.