The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to ...SARS-CoV-2 and the severity of COVID-19
, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases
. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Leaf form and photosynthesis Smith, W.K. (University of Wyoming, Laramie, WY.); Vogelmann, T.C; DeLucia, E.H ...
Bioscience,
(Dec 1997), 19971201, 1997-12-00, Letnik:
47, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Terrestrial plants responded to the amount of sunlight and stress in a given habitat by evolving properties in concert with leaf orientational capabilities.
Genetic alterations found in carcinomas can alter specific regulatory pathways and provide a selective growth advantage by activation of transforming oncogenes. A subset of these genes, including ...wild-type alleles of GLI or c-MYC, and activated alleles of RAS or beta-catenin, exhibit transforming activity when expressed in diploid epithelial RK3E cells in vitro. By in vitro transformation of these cells, the zinc finger protein GKLF/KLF-4 was recently identified as a novel oncogene. Although GKLF is normally expressed in superficial, differentiating epithelial cells of the skin, oral mucosa, and gut, expression is consistently up-regulated in dysplastic epithelium and in squamous cell carcinoma of the oral cavity. In the current study, we used in situ hybridization, Northern blot analysis, and immunohistochemistry to detect GKLF at various stages of tumor progression in the breast, prostate, and colon. Overall, expression of GKLF mRNA was detected by in situ hybridization in 21 of 31 cases (68%) of carcinoma of the breast. Low-level expression of GKLF mRNA was observed in morphologically normal (uninvolved) breast epithelium adjacent to tumor cells. Increased expression was observed in neoplastic cells compared with adjacent uninvolved epithelium for 14 of 19 cases examined (74%). Ductal carcinoma in situ exhibited similar expression as invasive carcinoma, suggesting that GKLF is activated prior to invasion through the basement membrane. Expression as determined by Northern blot was increased in most breast tumor cell lines and in immortalized human mammary epithelial cells when these were compared with finite-life span human mammary epithelial cells. Alteration of GKLF expression was confirmed by the use of a novel monoclonal antibody that detected the protein in normal and neoplastic tissues in a distribution consistent with localization of the mRNA. In contrast to most breast tumors, expression of GKLF in tumor cells of colorectal or prostatic carcinomas was reduced or unaltered compared with normal epithelium. The results demonstrate that GKLF expression in epithelial compartments is altered in a tissue-type specific fashion during tumor progression, and suggest that increased expression of GKLF mRNA and protein may contribute to the malignant phenotype of breast tumors.
Food grade fisheries have reached their sustainable limits while aquaculture production has increased to meet consumer demands. However, for growth in aquaculture to continue and utilise sustainable, ...feeding ingredients, alternatives to fish oil (FO), the predominant lipid component of fish diets, must be developed. Therefore, there is currently considerable interest in the regulation of fatty acid metabolism in fish in order to determine strategies for the best use of plant oils in diets for commercially important cultured fish species. Plant oils are characteristically rich in C
18 polyunsaturated fatty acids (PUFA) but devoid of C
20 and C
22 highly unsaturated fatty acids (HUFA) found in FO. The fatty acyl desaturase enzyme activities involved in the biosynthesis of HUFA from PUFA are known to be under nutritional regulation and can be increased in fish fed diets rich in plant oils. However, fatty acid desaturase activity is also known to be modulated by water temperature in fish. The present study aimed to investigate the interaction between water temperature and diet in the regulation of fatty acid metabolism in rainbow trout. Trout, acclimatized to 7, 11 or 15 °C, were fed for 4 weeks on diets in which the FO was replaced in a graded manner by palm oil. At the end of the trial, fatty acyl desaturation/elongation and β-oxidation activities were determined in isolated hepatocytes and intestinal enterocytes using 1-
14C18:3n-3 as substrate, and samples of liver were collected for analysis of lipid and fatty acid composition. The most obvious effect of temperature was that fatty acid desaturation/elongation and β-oxidation were reduced in both hepatocytes and intestinal enterocytes from fish maintained at the highest water temperature (15 °C). There were differences between the two tissues with the highest desaturation/elongation and β-oxidation activities tending to be in fish held at 11 °C in the case of hepatocytes, but 7 °C in enterocytes. Correlations between fatty acid metabolism and dietary palm oil were most clearly observed in desaturation/elongation activities in both hepatocytes and enterocytes at 11 °C. The highest β-oxidation activities were generally observed in fish fed FO alone in both hepatocytes and enterocytes with palm oil having differential effects in the two cell types.
ABSTRACT In area and depth, the Pan-STARRS1 (PS1) 3π survey is unique among many-epoch, multi-band surveys and has enormous potential for the all-sky identification of variable sources. PS1 has ...observed the sky typically seven times in each of its five bands (grizy) over 3.5 years, but unlike SDSS, not simultaneously across the bands. Here we develop a new approach for quantifying statistical properties of non-simultaneous, sparse, multi-color light curves through light curve structure functions, effectively turning PS1 into a ∼35-epoch survey. We use this approach to estimate variability amplitudes and timescales ( r, τ) for all point sources brighter than rP1 = 21.5 mag in the survey. With PS1 data on SDSS Stripe 82 as "ground truth," we use a Random Forest Classifier to identify QSOs and RR Lyrae based on their variability and their mean PS1 and WISE colors. We find that, aside from the Galactic plane, QSO and RR Lyrae samples of purity ∼75% and completeness ∼92% can be selected. On this basis we have identified a sample of ∼1,000,000 QSO candidates, as well as an unprecedentedly large and deep sample of ∼150,000 RR Lyrae candidates with distances from ∼10 to ∼120 kpc. Within the Draco dwarf spheroidal, we demonstrate a distance precision of 6% for RR Lyrae candidates. We provide a catalog of all likely variable point sources and likely QSOs in PS1, a total of 25.8 × 106 sources.
Summary
Grasses rank among the world’s most ecologically and economically important plants. Repeated evolution of the C
4
syndrome has made photosynthesis highly efficient in many grasses, inspiring ...intensive efforts to engineer the pathway into C
3
crops. However, comparative biology has been of limited use to this endeavor because of uncertainty in the number and phylogenetic placement of C
4
origins.
We built the most comprehensive and robust molecular phylogeny for grasses to date, expanding sampling efforts of a previous working group from 62 to 531 taxa, emphasizing the C
4
‐rich PACMAD (Panicoideae, Arundinoideae, Chloridoideae, Micrairoideae, Aristidoideae and Danthonioideae) clade. Our final matrix comprises
c.
5700 bp and is > 93% complete.
For the first time, we present strong support for relationships among all the major grass lineages. Several new C
4
lineages are identified, and previously inferred origins confirmed. C
3
/C
4
evolutionary transitions have been highly asymmetrical, with 22–24 inferred origins of the C
4
pathway and only one potential reversal.
Our backbone tree clarifies major outstanding systematic questions and highlights C
3
and C
4
sister taxa for comparative studies. Two lineages have emerged as hotbeds of C
4
evolution. Future work in these lineages will be instrumental in understanding the evolution of this complex trait.
The growth of wind power production in the electricity portfolio is striving to meet ambitious targets set, for example by the EU, to reduce greenhouse gas emissions by 20% by 2020. Huge investments ...are now being made in new offshore wind farms around UK coastal waters that will have a major impact on the GB electrical supply. Representations of the UK wind field in syntheses which capture the inherent structure and correlations between different locations including offshore sites are required. Here, Vector Auto-Regressive (VAR) models are presented and extended in a novel way to incorporate offshore time series from a pan-European meteorological model called COSMO, with onshore wind speeds from the MIDAS dataset provided by the British Atmospheric Data Centre. Forecasting ability onshore is shown to be improved with the inclusion of the offshore sites with improvements of up to 25% in RMS error at 6 h ahead. In addition, the VAR model is used to synthesise time series of wind at each offshore site, which are then used to estimate wind farm capacity factors at the sites in question. These are then compared with estimates of capacity factors derived from the work of Hawkins et al. (2011). A good degree of agreement is established indicating that this synthesis tool should be useful in power system impact studies.
•Nitrous oxide emissions and emission factors from 3 UK arable sites were measured.•Mitigation methods to reduce nitrous oxide emissions were investigated.•Use of the nitrification inhibitor DCD ...significantly reduced emissions.•Emission factors at 2 sites were much lower than the IPCC 1% value.•Emission factors as low as 0.20% were observed at sites experiencing low rainfall.
Cultivated agricultural soils are the largest anthropogenic source of nitrous oxide (N2O), a greenhouse gas approx. 298 times stronger than carbon dioxide. As agricultural land covers 40–50% of the earth’s surface agricultural N2O emissions could significantly influence future climate. The timing, amount and form of manufactured nitrogen (N) fertiliser applied to soils are major controls on N2O emission magnitude, and various methods are being investigated to quantify and reduce these emissions. A lack of measured N2O emission factors (EFs) means that most countries report N2O emissions using the IPCC’s Tier 1 methodology, where an EF of 1% is applied to mineral soils, regardless of soil type, climate, or location. The aim of this research was to generate evidence from experiments to contribute to improving the UK’s N2O agricultural inventory, by determining whether N2O EFs should vary across soil types and agroclimatic zones. Mitigation methods were also investigated, including assessing the impact of the nitrification inhibitor (NI) dicyandiamide (DCD), the application of more frequent smaller doses of fertiliser, and the impact of different rates and forms of manufactured N fertiliser. Nitrous oxide emissions were measured at one cropland site in Scotland and two in England for 12 months in 2011/2012, along with soil and environmental variables. Crop yield was also measured, and emission intensities were calculated for the contrasting fertiliser treatments. The greatest mean annual cumulative emissions from a range of ammonium nitrate (AN) fertiliser rates were measured at the Scottish site (2301g N2O-N ha−1), which experienced 822mm rainfall compared to 418mm and 472mm at the English sites, where cumulative annual emissions were lower (929 and 1152g N2O-N ha−1, respectively). Climate and soil mineral N influenced N2O emissions, with a combination of factors required to occur simultaneously to generate the greatest fluxes. Emissions were related to fertiliser N rate; however the trend was not linear. EFs for AN treatments varied between sites, but at both English sites were much lower than the 1% value used by the IPCC, and as low as 0.20%. DCD reduced AN- and urea-generated N2O emissions and yield-scaled emissions at all sites. AN application in more frequent smaller doses reduced emissions at all sites, however, the type of fertiliser (AN or urea) had no impact. A significant difference in mean annual cumulative emissions between sites reflected differences in rainfall, and suggests that location specific or rainfall driven emission estimates could be considered.
The electron-energy distribution in a Au film was measured with approx 700 fs time-resolved photoemission spectroscopy following laser heating by a 400 fs visible laser pulse. The measured ...distribution can be fitted by the Fermi--Dirac function at an elevated temperature except within 800 fs of the heating pulse (time-resolution limited), when a reproducible departure is observed. As a result, the relaxation of nonequilibrium electrons was found to be inadequately described by the standard electron--phonon coupling model.
Dielectronic satellite spectra of heliumlike argon, recorded with a high-resolution x-ray crystal spectrometer at the National Spherical Torus Experiment, were found to be inconsistent with existing ...predictions resulting in unacceptable values for the power balance and suggesting the unlikely existence of non-Maxwellian electron energy distributions. These problems were resolved with calculations from a new atomic code. It is now possible to perform reliable electron-temperature measurements and to eliminate the uncertainties associated with determinations of non-Maxwellian distributions.
PDF
