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- BL Lacertae objects: individual (TXS 0506+056, VER J0509+057) (1)
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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.
On 2017 September 22, the IceCube Neutrino Observatory reported the detection of the high-energy neutrino event IC 170922A, of potential astrophysical origin. It was soon determined that the neutrino direction was consistent with the location of the gamma-ray blazar TXS 0506+056. (3FGL J0509.4+ 0541), which was in an elevated gamma-ray emission state as measured by the Fermi satellite. Very Energetic Radiation Imaging Telescope Array System (VERITAS) observations of the neutrino/blazar region started on 2017 September 23 in response to the neutrino alert and continued through 2018 February 6. While no significant very-high-energy (VHE; E > 100 GeV) emission was observed from the blazar by VERITAS in the two-week period immediately following the IceCube alert, TXS 0506+ 056 was detected by VERITAS with a significance of 5.8 standard deviations (sigma) in the full 35 hr data set. The average photon flux of the source during this period was (8.9 +/- 1.6). x. 10(-12) cm(-2) s(-1), or 1.6% of the Crab Nebula flux, above an energy threshold of 110 GeV, with a soft spectral index of 4.8. +/-. 1.3.
A Search for Pulsed Very High-energy Gamma-Rays from 13 Young Pulsars in Archival VERITAS Data
(2019)
We conduct a search for periodic emission in the very high-energy (VHE) gamma-ray band (E > 100 GeV) from a total of 13 pulsars in an archival VERITAS data set with a total exposure of over 450 hr. The set of pulsars includes many of the brightest young gamma-ray pulsars visible in the Northern Hemisphere. The data analysis resulted in nondetections of pulsed VHE gamma-rays from each pulsar. Upper limits on a potential VHE gamma-ray flux are derived at the 95% confidence level above three energy thresholds using two methods. These are the first such searches for pulsed VHE emission from each of the pulsars, and the obtained limits constrain a possible flux component manifesting at VHEs as is seen for the Crab pulsar.
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.
The Great Nebula in Carina provides an exceptional view into the violent massive star formation and feedback that typifies giant H II regions and starburst galaxies. We have mapped the Carina star-forming complex in X-rays, using archival Chandra data and a mosaic of 20 new 60 ks pointings using the Chandra X-ray Observatory's Advanced CCD Imaging Spectrometer, as a testbed for understanding recent and ongoing star formation and to probe Carina's regions of bright diffuse X-ray emission. This study has yielded a catalog of properties of > 14,000 X-ray point sources;> 9800 of them have multiwavelength counterparts. Using Chandra's unsurpassed X-ray spatial resolution, we have separated these point sources from the extensive, spatially-complex diffuse emission that pervades the region; X-ray properties of this diffuse emission suggest that it traces feedback from Carina's massive stars. In this introductory paper, we motivate the survey design, describe the Chandra observations, and present some simple results, providing a foundation for the 15 papers that follow in this special issue and that present detailed catalogs, methods, and science results.
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world(1). Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenicBRCA1andBRCA2variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. <br /> Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
The majority of research on biodiversity ecosystem functioning in laboratories has concentrated on a few traits, but there is increasing evidence from the field that functional diversity controls ecosystem functioning more often than does species number. Given the importance of traits as predictors of niche complementarity and community structures, we (1) examine how the diversity sensu lato of forest trees, freshwater fishes and soil invertebrates might support ecosystem functioning and (2) discuss the relevance of productive biota for monophyletic assemblages (taxocenes).
In terrestrial ecosystems, correlating traits to abiotic factors is complicated by the appropriate choice of body-size distributions. Angiosperm and gymnosperm trees, for example, show metabolic incongruences in their respiration rates despite their pronounced macroecological scaling. Scaling heterotrophic organisms within their monophyletic assemblages seems more difficult than scaling autotrophs: in contrast to the generally observed decline of mass-specific metabolic rates with body mass within metazoans, soil organisms such as protozoans show opposite mass-specific trends.
At the community level, the resource demand of metazoans shapes multitrophic interactions. Hence, population densities and their food web relationships reflect functional diversity, but the influence of biodiversity on stability and ecosystem functioning remains less clear. We focused on fishes in 18 riverine food webs, where the ratio of primary versus secondary extinctions (hereafter, 'extinction partitioning') summarizes the responses of fish communities to primary species loss (deletions) and its consequences. Based on extinction partitioning, our high-diversity food webs were just as (or even more) vulnerable to extinctions as low-diversity food webs.
Our analysis allows us to assess consequences of the relocation or removal of fish species and to help with decision-making in sustainable river management. The study highlights that the topology of food webs (and not simply taxonomic diversity) plays a greater role in stabilizing the food web and enhancing ecological services than is currently acknowledged.
Scientific theories of how subduction and plate tectonics began on Earth-and what the tectonic structure of Earth was before this-remain enigmatic and contentious(1). Understanding viable scenarios for the onset of subduction and plate tectonics(2,3) is hampered by the fact that subduction initiation processes must have been markedly different before the onset of global plate tectonics because most present-day subduction initiation mechanisms require acting plate forces and existing zones of lithospheric weakness, which are both consequences of plate tectonics(4). However, plume-induced subduction initiation(5-9) could have started the first subduction zone without the help of plate tectonics. Here, we test this mechanism using high-resolution three-dimensional numerical thermomechanical modelling. We demonstrate that three key physical factors combine to trigger self-sustained subduction: (1) a strong, negatively buoyant oceanic lithosphere; (2) focused magmatic weakening and thinning of lithosphere above the plume; and (3) lubrication of the slab interface by hydrated crust. We also show that plume-induced subduction could only have been feasible in the hotter early Earth for old oceanic plates. In contrast, younger plates favoured episodic lithospheric drips rather than self-sustained subduction and global plate tectonics.