Biases in the Experimental Annotations of Protein Function and their Effect on Our Understanding of Protein Function Space

The ongoing functional annotation of proteins relies upon the work of curators to capture experimental findings from scientific literature and apply them to protein sequence and structure data. However, with the increasing use of high-throughput experimental assays, a small number of experimental studies dominate the functional protein annotations collected in databases. Here we investigate just how prevalent is the "few articles -- many proteins" phenomenon. We examine the experimentally validated annotation of proteins provided by several groups in the GO Consortium, and show that the distribution of proteins per published study is exponential, with 0.14% of articles providing the source of annotations for 25% of the proteins in the UniProt-GOA compilation. Since each of the dominant articles describes the use of an assay that can find only one function or a small group of functions, this leads to substantial biases in what we know about the function of many proteins. Mass-spectrometry, microscopy and RNAi experiments dominate high throughput experiments. Consequently, the functional information derived from these experiments is mostly of the subcellular location of proteins, and of the participation of proteins in embryonic developmental pathways. For some organisms, the information provided by different studies overlap by a large amount. We also show that the information provided by high throughput experiments is less specific than those provided by low throughput experiments. Given the experimental techniques available, certain biases in protein function annotation due to high-throughput experiments are unavoidable. Knowing that these biases exist and understanding their characteristics and extent is important for database curators, developers of function annotation programs, and anyone who uses protein function annotation data to plan experiments.Comment: Accepted to PLoS Computational Biology. Press embargo applies. v4: text corrected for style and supplementary material inserte

Discovery of the supernova remnant G351.0-5.4

Context. While searching the NRAO VLA Sky Survey (NVSS) for diffuse radio emission, we have serendipitously discovered extended radio emission close to the Galactic plane. The radio morphology suggests the presence of a previously unknown Galactic supernova remnant. An unclassified {\gamma}-ray source detected by EGRET (3EG J1744-3934) is present in the same location and may stem from the interaction between high-speed particles escaping the remnant and the surrounding interstellar medium. Aims. Our aim is to confirm the presence of a previously unknown supernova remnant and to determine a possible association with the {\gamma}-ray emission 3EG J1744-3934. Methods. We have conducted optical and radio follow-ups of the target using the Dark Energy Camera (DECam) on the Blanco telescope at Cerro Tololo Inter-American Observatory (CTIO) and the Giant Meterwave Radio Telescope (GMRT). We then combined these data with archival radio and {\gamma}-ray observations. Results. While we detected the extended emission in four different radio bands (325, 1400, 2417, and 4850 MHz), no optical counterpart has been identified. Given its morphology and brightness, it is likely that the radio emission is caused by an old supernova remnant no longer visible in the optical band. Although an unclassified EGRET source is co-located with the supernova remnant, Fermi-LAT data do not show a significant {\gamma}-ray excess that is correlated with the radio emission. However, in the radial distribution of the {\gamma}-ray events, a spatially extended feature is related with SNR at a confidence level $\sim 1.5$ {\sigma}. Conclusions. We classify the newly discovered extended emission in the radio band as the old remnant of a previously unknown Galactic supernova: SNR G351.0-5.4.Comment: 6 pages, 6 figures, accepted A&

Modelling spatial and inter-annual variations of nitrous oxide emissions from UK cropland and grasslands using DailyDayCent

This work contributes to the Defra funded projects AC0116: ‘Improving the nitrous oxide inventory’, and AC0114: ‘Data Synthesis, Management and Modelling’. Funding for this work was provided by the UK Department for Environment, Food and Rural Affairs (Defra) AC0116 and AC0114, the Department of Agriculture, Environment and Rural Affairs for Northern Ireland, the Scottish Government and the Welsh Government. Rothamsted Research receives strategic funding from the Biotechnology and Biological Sciences Research Council. This study also contributes to the projects: N-Circle (BB/N013484/1), U-GRASS (NE/M016900/1) and GREENHOUSE (NE/K002589/1).Peer reviewedPublisher PD

Global Research Alliance N2O chamber methodology guidelines: Recommendations for deployment and accounting for sources of variability

Adequately estimating soil nitrous oxide (N2O) emissions using static chambers is challenging due to the high spatial variability and episodic nature of these fluxes. This paper discusses how static chamber N2O experiments can be designed, and protocols implemented, to better account for this variability and reduce the uncertainty of N2O emission estimates. It is part of a series of papers in this special issue, each discussing a particular aspect of N2O chamber methodology. Aspects of experimental design and sampling affected by spatial variability include site selection, and chamber layout, size and areal coverage. Where used, treatment application adds a further level of spatial variability. Time of day, frequency and duration of sampling (both in terms of individual chamber closures and overall experiment duration) affect the temporal variability captured. In addition, we present best practice recommendations for experimental chamber installation and sampling protocols to minimise the introduction of further uncertainty. To obtain the best N2O emission estimates, resources should be allocated to minimise the overall uncertainty in line with experiment objectives. In some cases, this will mean prioritising individual flux measurements and increasing their accuracy and precision by, for example, collecting ≥4 headspace samples during each chamber closure. However, where N2O fluxes are exceptionally spatially variable, for example, in heterogeneous agricultural landscapes, such as uneven and woody grazed pastures, using available resources to deploy more chambers with fewer headspace samples per chamber may be beneficial. Similarly, for particularly episodic N2O fluxes, generated for example by irrigation or freeze-thaw cycles, increasing chamber sampling frequency will improve the accuracy and reduce the uncertainty of temporally interpolated N2O fluxe

An assessment of nitrification inhibitors to reduce nitrous oxide emissions from UK agriculture

A trial was conducted consisting of 14 experiments across sites in England of contrasting soil type and annual rainfall to assess the effectiveness of nitrification inhibitors (predominantly dicyandiamide (DCD) but limited assessment also of 3, 4-dimethylpyrazole phosphate (DMPP) and a commercial product containing two pyrazole derivatives) in reducing direct nitrous oxide (N _2 O) emissions from fertilizer nitrogen (N), cattle urine and cattle slurry applications to land. Measurements were also made of the impact on ammonia (NH _3 ) volatilization, nitrate (NO _3 ^− ) leaching, crop yield and crop N offtake. DCD proved to be very effective in reducing direct N _2 O emissions following fertilizer and cattle urine applications, with mean reduction efficiencies of 39, 69 and 70% for ammonium nitrate, urea and cattle urine, respectively. When included with cattle slurry a mean, non-significant reduction of 56% was observed. There were no N _2 O emission reductions observed from the limited assessments of the other nitrification inhibitors. Generally, there were no impacts of the nitrification inhibitors on NH _3 volatilization, NO _3 ^− leaching, crop yield or crop N offtake. Use of DCD could give up to 20% reduction in N _2 O emissions from UK agriculture, but cost-effective delivery mechanisms are required to encourage adoption by the sector. Direct N _2 O emissions from the studied sources were substantially lower than IPCC default values and development of UK country-specific emission factors for use in inventory compilation is warranted

Towards country-specific nitrous oxide emission factors for manures applied to arable and grassland soils in the UK

Nitrous oxide (N2O) emission factors (EFs) were calculated from measurements of emissions from livestock manures applied to UK arable crops and grassland as part of a wider research programme to reduce uncertainty in the UK national agricultural N2O inventory and to enhance regional inventory reporting through increased understanding of processes and factors controlling emissions. Field studies were undertaken between 2011 and 2013 at 3 arable and 3 grassland sites in the UK. Nitrous oxide emissions were measured following the autumn and spring application of different manures (pig slurry, cattle slurry, cattle farmyard manure (FYM), pig FYM, poultry layer manure, and broiler litter) at typical rates, using representative manure application and soil incorporation methods. In addition, ammonia emissions and nitrate leaching losses (1 site on a light sandy soil) were measured to calculate indirect N2O losses. IPCC comparable, direct N2O EFs ranged from −0.05 to 2.30% of total nitrogen applied, with the variability driven by a range of factors including differences in manure composition, application method, incorporation and climatic conditions. When data from the autumn applications were pooled, the mean N2O EF from poultry manure (1.52%) was found to be greater (P < 0.001) than from FYM (0.37%) and slurry (0.72%), with no difference found (P = 0.784) in the EF for bandspread compared with surface broadcast slurry application, and no effect (P = 0.328) of the nitrification inhibitor, Dicyandiamide (DCD). For the spring applications, the mean N2O EF for bandspread slurry (0.56%) was greater (P = 0.028) than from surface broadcast slurry (0.31%), but there were no differences (P = 0.212) in the mean N2O EFs from poultry manure (0.52%), slurry (0.44%), and FYM (0.22%). The study did confirm, however, that DCD reduced N2O emissions from slurries applied in the spring by 45%. EF data from this project have been used in the derivation of robust Tier 2 country specific EFs for inclusion in the UK national agriculture greenhouse gas inventory

The Lick AGN Monitoring Project 2011: Reverberation Mapping of Markarian 50

The Lick AGN Monitoring Project 2011 observing campaign was carried out over the course of 11 weeks in Spring 2011. Here we present the first results from this program, a measurement of the broad-line reverberation lag in the Seyfert 1 galaxy Mrk 50. Combining our data with supplemental observations obtained prior to the start of the main observing campaign, our dataset covers a total duration of 4.5 months. During this time, Mrk 50 was highly variable, exhibiting a maximum variability amplitude of a factor of 4 in the U-band continuum and a factor of 2 in the H-beta line. Using standard cross-correlation techniques, we find that H-beta and H-gamma lag the V-band continuum by tau_cen = 10.64(-0.93,+0.82) and 8.43(-1.28,+1.30) days, respectively, while the lag of He II 4686 is unresolved. The H-beta line exhibits a symmetric velocity-resolved reverberation signature with shorter lags in the high-velocity wings than in the line core, consistent with an origin in a broad-line region dominated by orbital motion rather than infall or outflow. Assuming a virial normalization factor of f=5.25, the virial estimate of the black hole mass is (3.2+-0.5)*10^7 solar masses. These observations demonstrate that Mrk 50 is among the most promising nearby active galaxies for detailed investigations of broad-line region structure and dynamics.Comment: Accepted for publication in ApJ Letters. 6 pages, 4 figure

Hubble Space Telescope Observations of Field Ultracool Dwarfs at High Galactic Latitude

We present a sample of 17 newly discovered ultracool dwarf candidates later than ~M8, drawn from 231.90 arcmin2 of {\it Hubble Space Telescope} Wide Field Camera 3 infrared imaging. By comparing the observed number counts for 17.5<J_125<25.5 AB mag to an exponential disk model, we estimate a vertical scale height of z_scl=290 +- 25 (random) +- 30 (systematic) pc for a binarity fraction of f_b=0. While our estimate is roughly consistent with published results, we suggest that the differences can be attributed to sample properties, with the present sample containing far more substellar objects than previous work. We predict the object counts should peak at J_{125}~24 AB mag due to the exponentially-declining number density at the edge of the disc. We conclude by arguing that trend in scale height with spectral type may breakdown for brown dwarfs since they do not settle onto the main sequence.Comment: 9 pages, 6 figures, 3 tables, accepted to ApJ (v2 is consistent with Referee changes