Refine
Has Fulltext
- no (7)
Language
- English (7)
Is part of the Bibliography
- yes (7)
Keywords
- Antifreeze protein (1)
- Cell-free protein synthesis (1)
- Galaxy: abundances (1)
- Galaxy: evolution (1)
- Galaxy: formation (1)
- Galaxy: halo (1)
- Ice binding protein (1)
- Ice structuring protein (1)
- In vitro translation (1)
- galaxies: dwarf (1)
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.
We present the Pristine survey, a new narrow-band photometric survey focused on the metallicity-sensitive Ca H&K lines and conducted in the Northern hemisphere with the wide-field imager MegaCam on the Canada-France-Hawaii Telescope. This paper reviews our overall survey strategy and discusses the data processing and metallicity calibration. Additionally we review the application of these data to the main aims of the survey, which are to gather a large sample of the most metal-poor stars in the Galaxy, to further characterize the faintest Milky Way satellites, and to map the (metal-poor) substructure in the Galactic halo. The current Pristine footprint comprises over 1000 deg(2) in the Galactic halo ranging from b similar to 30 degrees to similar to 78 degrees and covers many known stellar substructures. We demonstrate that, for Sloan Digital Sky Survey (SDSS) stellar objects, we can calibrate the photometry at the 0.02-mag level. The comparison with existing spectroscopic metallicities from SDSS/Sloan Extension for Galactic Understanding and Exploration (SEGUE) and Large Sky Area Multi-Object Fiber Spectroscopic Telescope shows that, when combined with SDSS broad-band g and i photometry, we can use the CaHK photometry to infer photometric metallicities with an accuracy of similar to 0.2 dex from [Fe/H] = -0.5 down to the extremely metal-poor regime ([Fe/H] < -3.0). After the removal of various contaminants, we can efficiently select metal-poor stars and build a very complete sample with high purity. The success rate of uncovering [Fe/H](SEGUE) < -3.0 stars among [Fe/H](Pristine) < -3.0 selected stars is 24 per cent, and 85 per cent of the remaining candidates are still very metal poor ([Fe/H]<-2.0). We further demonstrate that Pristine is well suited to identify the very rare and pristine Galactic stars with [Fe/H] < -4.0, which can teach us valuable lessons about the early Universe.
Functional evaluation of candidate ice structuring proteins using
cell-free expression systems
(2013)
Ice structuring proteins (ISPs) protect organisms from damage or death by freezing. They depress the non-equilibrium freezing point of water and prevent recrystallization, probably by binding to the surface of ice crystals. Many ISPs have been described and it is likely that many more exist in nature that have not yet been identified. ISPs come in many forms and thus cannot be reliably identified by their structure or consensus ice-binding motifs. Recombinant protein expression is the gold standard for proving the activity of a candidate ISP. Among existing expression systems, cell-free protein expression is the simplest and gives the fastest access to the protein of interest, but selection of the appropriate cell-free expression system is crucial for functionality. Here we describe cell-free expression methods for three ISPs that differ widely in structure and glycosylation status from three organisms: a fish (Macrozoarces americanus), an insect (Dendroides canadensis) and an alga (Chlamydomonas sp. CCMP681). We use both prokaryotic and eukaryotic expression systems for the production of ISPs. An ice recrystallization inhibition assay is used to test functionality. The techniques described here should improve the success of cell-free expression of ISPs in future applications. (C) 2012 Elsevier B.V. All rights reserved.
The cryosphere in mountain regions is rapidly declining, a trend that is expected to accelerate over the next several decades due to anthropogenic climate change. A cascade of effects will result, extending from mountains to lowlands with associated impacts on human livelihood, economy, and ecosystems. With rising air temperatures and increased radiative forcing, glaciers will become smaller and, in some cases, disappear, the area of frozen ground will diminish, the ratio of snow to rainfall will decrease, and the timing and magnitude of both maximum and minimum streamflow will change. These changes will affect erosion rates, sediment, and nutrient flux, and the biogeochemistry of rivers and proglacial lakes, all of which influence water quality, aquatic habitat, and biotic communities. Changes in the length of the growing season will allow low-elevation plants and animals to expand their ranges upward. Slope failures due to thawing alpine permafrost, and outburst floods from glacier-and moraine-dammed lakes will threaten downstream populations.Societies even well beyond the mountains depend on meltwater from glaciers and snow for drinking water supplies, irrigation, mining, hydropower, agriculture, and recreation. Here, we review and, where possible, quantify the impacts of anticipated climate change on the alpine cryosphere, hydrosphere, and biosphere, and consider the implications for adaptation to a future of mountains without permanent snow and ice.
Consequences of twenty-first-century policy for multi-millennial climate
and sea-level change
(2016)
Most of the policy debate surrounding the actions needed to mitigate and adapt to anthropogenic climate change has been framed by observations of the past 150 years as well as climate and sea-level projections for the twenty-first century. The focus on this 250-year window, however, obscures some of the most profound problems associated with climate change. Here, we argue that the twentieth and twenty-first centuries, a period during which the overwhelming majority of human-caused carbon emissions are likely to occur, need to be placed into a long-term context that includes the past 20 millennia, when the last Ice Age ended and human civilization developed, and the next ten millennia, over which time the projected impacts of anthropogenic climate change will grow and persist. This long-term perspective illustrates that policy decisions made in the next few years to decades will have profound impacts on global climate, ecosystems and human societies - not just for this century, but for the next ten millennia and beyond.
The structure of bulk liquid water was recently probed by x-ray scattering below the temperature limit of homogeneous nucleation (T-H) of similar to 232 K [J. A. Sellberg et al., Nature 510, 381-384 (2014)]. Here, we utilize a similar approach to study the structure of bulk liquid water below T-H using oxygen K-edge x-ray emission spectroscopy (XES). Based on previous XES experiments [T. Tokushima et al., Chem. Phys. Lett. 460, 387-400 (2008)] at higher temperatures, we expected the ratio of the 1b(1)' and 1b(1)" peaks associated with the lone-pair orbital in water to change strongly upon deep supercooling as the coordination of the hydrogen (H-) bonds becomes tetrahedral. In contrast, we observed only minor changes in the lone-pair spectral region, challenging an interpretation in terms of two interconverting species. A number of alternative hypotheses to explain the results are put forward and discussed. Although the spectra can be explained by various contributions from these hypotheses, we here emphasize the interpretation that the line shape of each component changes dramatically when approaching lower temperatures, where, in particular, the peak assigned to the proposed disordered component would become more symmetrical as vibrational interference becomes more important. (C) 2015 AIP Publishing LLC.
We report on oxygen K-edge soft x-ray emission spectroscopy from a liquid water jet at the Linac Coherent Light Source. We observe significant changes in the spectral content when tuning over a wide range of incident x-ray fluences. In addition the total emission yield decreases at high fluences. These modifications result from reabsorption of x-ray emission by valence-excited molecules generated by the Auger cascade. Our observations have major implications for future x-ray emission studies at intense x-ray sources. We highlight the importance of the x-ray pulse length with respect to the core-hole lifetime.