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- Laboratory astrophysics (2)
- Sentinel-1 InSAR (2)
- Sobo-Sise Island (2)
- Yedoma uplands (2)
- active layer (2)
- permafrost thaw subsidence (2)
- summer heave (2)
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- Booster cavity (1)
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Fibroblast growth factor 23 (FGF23) is a proteohormone regulating renal phosphate transport and vitamin D metabolism as well as inducing left heart hypertrophy. FGF23-deficient mice suffer from severe tissue calcification, accelerated aging and a myriad of aging-associated diseases. Bone cells produce FGF23 upon store-operated calcium ion entry (SOCE) through the calcium selective ion channel Orai1. AMP-activated kinase (AMPK) is a powerful energy sensor helping cells survive states of energy deficiency, and AMPK down-regulates Orai1. Here we investigated the role of AMPK in FGF23 production. Fgf23 gene transcription was analyzed by qRT-PCR and SOCE by fluorescence optics in UMR106 osteoblast-like cells while the serum FGF23 concentration and phosphate metabolism were assessed in AMPKa1-knockout and wild-type mice. The AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) down-regulated, whereas the AMPK inhibitor, dorsomorphin dihydrochloride (compound C) and AMPK gene silencing induced Fgf23 transcription. AICAR decreased membrane abundance of Orai1 and SOCE. SOCE inhibitors lowered Fgf23 gene expression induced by AMPK inhibition. AMPKa1-knockout mice had a higher serum FGF23 concentration compared to wild-type mice. Thus, AMPK participates in the regulation of FGF23 production in vitro and in vivo. The inhibitory effect of AMPK on FGF23 production is at least in part mediated by Orai1-involving SOCE.
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
In mammals the composition of milk changes during early lactation, with a rapid decline of fat-soluble vitamins and a continuous increase in total lipids. The mechanisms underlying this phenomenon are not well understood, but might involve selective mechanisms related to mammary uptake or secretion into the milk. Since carotenoids are specifically distributed among the lipoprotein fractions in plasma, the simultaneous determination of carotenoids in plasma, lipoprotein fractions and milk might offer an opportunity to gain insight into this phenomenon. In 21 healthy mothers carotenoids in plasma and lipoprotein fractions were investigated at day 2 and 19 and milk on day 4 and 19 after delivery. Plasma levels of alpha-tocopherol and cholesterol as well as lutein, zeaxanthin and cryptoxanthin were significantly lower later in lactation (day 19) than shortly after birth (P < 0.01). The stage of lactation had no effect on the distribution of carotenoids and -tocopherol among the plasma lipoprotein fractions. In milk, triacylglycerol increased (P < 0.01). In contrast, levels of carotenoids, alpha- tocopherol and vitamin A were highest in colostrum and declined (P < 0.01). Because the magnitude of decrease was not the same in all carotenoids, the carotenoid pattern changed substantially. In colostrum the carotenoid pattern resembled those of plasma and the low- density lipoprotein fraction. In mature milk it was similar to the pattern found in the high density lipoprotein fraction. Based on these observations a selective mechanism might be responsible for the transfer of these components in milk involving different lipoprotein fractions at specific times of lactation
Background/Aims: The renal function, including the excretion of low-molecular-weight proteins, changes during pregnancy and may cause a urinary excretion of retinol-binding protein (RBP). Whether it is accompanied by a substantial loss of vitamin A ( retinol) has not been established yet. We therefore determined the excretion of retinol and RBP in urine of pregnant women. Methods: The study involved analyses of urine samples from 40 healthy pregnant women and 29 women with pregnancy complications during the third trimester. Analyses of plasma and urine of 7 healthy women and 5 women with pregnancy complications were also carried out 6 weeks antepartum, at time of delivery and 1 week postpartum. Results: Urinary retinol was higher in women who suffered from pregnancy disorders with an influence on maternal metabolism ( p < 0.01). RBP was excreted at substantial concentrations in the urine of all 69 women, but there were no differences between the groups. Women with a concomitant excretion of retinol had higher levels of urinary RBP than those without a retinol excretion ( p < 0.05). Differences in plasma retinol and RBP were not significant. Conclusion: The excretion of urinary retinol may increase significantly during pregnancy complications, which needs further clarification to which extent this condition may negatively affect the vitamin A status in such women. Copyright (C) 2004 S. Karger AG, Basel
Yedoma-extremely ice-rich permafrost with massive ice wedges formed during the Late Pleistocene-is vulnerable to thawing and degradation under climate warming. Thawing of ice-rich Yedoma results in lowering of surface elevations. Quantitative knowledge about surface elevation changes helps us to understand the freeze-thaw processes of the active layer and the potential degradation of Yedoma deposits. In this study, we use C-band Sentinel-1 InSAR measurements to map the elevation changes over ice-rich Yedoma uplands on Sobo-Sise Island, Lena Delta with frequent revisit observations (as short as six or 12 days). We observe significant seasonal thaw subsidence during summer months and heterogeneous inter-annual elevation changes from 2016-17. We also observe interesting patterns of stronger seasonal thaw subsidence on elevated flat Yedoma uplands by comparing to the surrounding Yedoma slopes. Inter-annual analyses from 2016-17 suggest that our observed positive surface elevation changes are likely caused by the delayed progression of the thaw season in 2017, associated with mean annual air temperature fluctuations.
Bulk electron transport and charge injection in a high mobility n-type semiconducting polymer
(2010)
Bulk electron transport in a high mobility n-type polymer is studied by time-of-flight photocurrent measurements and electron-only devices. Bulk electron mobilities of similar to 5 x 10(-3) cm(2)/Vs are obtained. The analysis of the electron currents suggests the presence of an injection barrier for all conventionally used low workfunction cathodes.