Structure-Templated Predictions of Novel Protein Interactions from Sequence Information

The multitude of functions performed in the cell are largely controlled by a set of carefully orchestrated protein interactions often facilitated by specific binding of conserved domains in the interacting proteins. Interacting domains commonly exhibit distinct binding specificity to short and conserved recognition peptides called binding profiles. Although many conserved domains are known in nature, only a few have well-characterized binding profiles. Here, we describe a novel predictive method known as domain–motif interactions from structural topology (D-MIST) for elucidating the binding profiles of interacting domains. A set of domains and their corresponding binding profiles were derived from extant protein structures and protein interaction data and then used to predict novel protein interactions in yeast. A number of the predicted interactions were verified experimentally, including new interactions of the mitotic exit network, RNA polymerases, nucleotide metabolism enzymes, and the chaperone complex. These results demonstrate that new protein interactions can be predicted exclusively from sequence information

Late night salivary cortisol and cortisone should be the initial screening test for Cushing’s syndrome

Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late night salivary cortisol (LNSC) is recommended as a first line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy1. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low dose dexamethasone suppression test and 24-hour urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients).LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/l the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home.We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS

Storylines of UK drought based on the 2010–2012 event

Spatially extensive multi-year hydrological droughts cause significant environmental stress. The UK is expected to remain vulnerable to future multi-year droughts under climate change. Existing approaches to quantify hydrological impacts of climate change often rely solely on global climate model (GCM) projections following different emission scenarios. This may miss out low-probability events with significant impacts. As a means of exploring such events, physical climate storyline approaches aim to quantify physically coherent articulations of how observed events could hypothetically have unfolded in alternative ways. This study uses the 2010–2012 drought, the most recent period of severe hydrological drought in the UK, as a basis and analyses storylines based on changes to (1) precondition severity, (2) temporal drought sequence, and (3) climate change. Evidence from multiple storylines shows that the maximum intensity, mean deficit, and duration of the 2010–2012 drought were highly influenced by its meteorological preconditions prior to drought inception, particularly for northern catchments at shorter timescales. The influence of progressively drier preconditions reflects both the spatial variation in drought preconditions and the role of physical catchment characteristics, particularly hydrogeology in the propagation of multi-year droughts. There are two plausible storylines of an additional dry year with dry winter conditions repeated either before the observed drought or replacing the observed dramatic drought termination confirm the vulnerability of UK catchments to a “third dry winter” storyline. Applying the UKCP18 climate projections, we find that drought conditions worsen with global warming with a mitigation of drought conditions by wetter winters in northern catchments at high warming levels. Comparison of the storylines with a benchmark drought (1975–1976) and a protracted multi-year drought (1989–1993) shows that, for each storyline (including the climate change storylines), drought conditions could have matched and exceeded those experienced during the past droughts at catchments across the UK, particularly for southern catchments. The construction of storylines based on observed events can complement existing methods to stress test UK catchments against plausible unrealised droughts

Landuse and soil degradation in the southern Maya lowlands, from Pre-Classic to Post-Classic times : The case of La Joyanca (Petén, Guatemala)

International audienceThis work focuses on the impact of Maya agriculture on soil degradation. In site and out site studies in the area of the city of La Joyanca (NW Petén) show that "Maya clays" do not constitute a homogeneous unit, but represent a complex sedimentary record. A high resolution analysis leads us to document changes in rates and practices evolving in time in relation with major socio-political and economic changes. It is possible to highlight extensive agricultural practices between Early Pre-classical to Late Pre-classical times. Intensification occurs in relation with reduction of the fallow duration during Pre-classic to Classic periods. The consequences of these changes on soil erosion are discussed. However, it does not seem that the agronomic potential of the soils was significantly degraded before the end of the Classic period

Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers

"This is the peer reviewed version of the following article: Gottselig, N., W. Amelung, J. W. Kirchner, R. Bol, W. Eugster, S. J. Granger, C. Hernández-Crespo, et al. 2017. Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers. Global Biogeochemical Cycles 31 (10). American Geophysical Union (AGU): 1592 1607. doi:10.1002/2017gb005657, which has been published in final form at https://doi.org/10.1002/2017GB005657. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (similar to 1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 +/- 5% (Si) and 53 +/- 21% (Fe; mean +/- SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe-to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.The authors gratefully acknowledge the assistance of the following people in locating suitable sampling sites, contacting site operators, performing the sampling, and providing data: A. Avila Castells (Autonomous University of Barcelona), R. Batalla (University of Lleida), P. Blomkvist (Swedish University of Agricultural Sciences), H. Bogena (Julich Research Center), A.K. Boulet (University of Aveiro), D. Estany (University of Lleida), F. Garnier (French National Institute of Agricultural Research), H.J. Hendricks-Franssen (Research Center Julich), L. JacksonBlake (James Hutton Institute, NIVA), T. Laurila (Finnish Meteorological Institute), A. Lindroth (Lund University), M.M. Monerris (Universitat Politecnica de Valencia), M. Ottosson Lofvenius (Swedish University of Agricultural Sciences), I. Taberman (Swedish University of Agricultural Sciences), F. Wendland (Research Center Julich), T. Zetterberg (Swedish University of Agricultural Sciences and The Swedish Environmental Research Institute, IVL) and further unnamed contributors. The Swedish Infrastructure for Ecosystem Science (SITES) and the Swedish Integrated Monitoring, the latter financed by the Swedish Environmental Protection Agency, and ICOS Sweden have supported sampling and provided data for the Swedish sites. J.J.K. gratefully acknowledges the support from CESAM (UID/AMB/50017/2013), funded by the FCT/MCTES (PIDDAC) with cofunding by FEDER through COMPETE. N.G. gratefully acknowledges all those who contributed to organizing and implementing the continental sampling. The raw data can be found at http://hdl.handle.net/2128/14937. This project was partly funded by the German Research Foundation (DFG KL2495/1-1).Gottselig, N.; Amelung, W.; Kirchner, J.; Bol, R.; Eugster, W.; Granger, S.; Hernández Crespo, C.... 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National scale evaluation of the InVEST nutrient retention model in the United Kingdom

A wide variety of tools aim to support decision making by modelling, mapping and quantifying ecosystem services. If decisions are to be properly informed, the accuracy and potential limitations of these tools must be well understood. However, dedicated studies evaluating ecosystem service models against empirical data are rare, especially over large areas. In this paper, we report on the national-scale assessment of a new ecosystem service model for nutrient delivery and retention, the InVEST Nutrient Delivery Ratio model. For 36 river catchments across the UK, we modelled total catchment export of phosphorus (P) and/or nitrogen (N) and compared model outputs to measurements derived from empirical water chemistry data. The model performed well in terms of relative magnitude of nutrient export among catchments (best Spearman’s rank correlation for N and P, respectively: 0.81 and 0.88). However, there was wide variation among catchments in the accuracy of the model, and absolute values of nutrient exports frequently showed high percentage differences between modelled and empirically-derived exports (best median absolute percentage difference for N and P, respectively: ± 64%, ± 44%). The model also showed a high degree of sensitivity to nutrient loads and hydrologic routing input parameters and these sensitivities varied among catchments. These results suggest that the InVEST model can provide valuable information on nutrient fluxes to decision makers, especially in terms of relative differences among catchments. However, caution is needed if using the absolute modelled values for decision-making. Our study also suggests particular attention should be paid to researching input nutrient loadings and retentions, and the selection of appropriate input data resolutions and threshold flow accumulation values. Our results also highlight how availability of empirical data can improve model calibration and performance assessment and reinforce the need to include such data in ecosystem service modelling studies

Storylines of UK drought based on the 2010-2012 event

Spatially extensive multi-year hydrological droughts cause significant environmental stress. The UK is expected to remain vulnerable to future multi-year droughts under climate change. Existing approaches to quantify hydrological impacts of climate change often rely solely on GCM projections following different emission scenarios. This may miss out low probability events with significant impacts. As a means of exploring such events, physical climate storyline approaches aim to quantify physically coherent articulations of how observed events could hypothetically have unfolded in alternative ways. This study uses the 2010-2012 drought, the most recent period of severe hydrological drought in the UK, as a basis, and analyses storylines based on changes to 1) precondition severity, 2) temporal drought sequence, and 3) climate change. Evidence from multiple storylines shows that maximum intensity, mean deficit and duration of the 2010-2012 drought were highly influenced by its meteorological preconditions prior to drought inception, particularly for northern catchments at shorter time scales. The influence of progressively drier preconditions reflects both spatial variation in drought preconditions and the role of physical catchment characteristics, particularly hydrogeology in the propagation of multi-year droughts. Two plausible storylines of an additional dry year with dry winter conditions repeated either before the observed drought or replacing the observed dramatic drought termination confirm the vulnerability of UK catchments to a “three dry winter” storyline. Applying the UKCP18 climate projections, we find that drought conditions worsen with global warming with a mitigation of drought conditions by wetter winters in northern catchments at high warming levels. Comparison of the storylines with a benchmark drought (1975-76) and a protracted multi-year drought (1989-93) shows that for each storyline (including the climate change storylines), drought conditions could have matched and exceeded those experienced during the past droughts at catchments across the UK, particularly for southern catchments. The construction of storylines based on observed events can complement existing methods to stress test UK catchments against plausible unrealized droughts

Tracking the methodological development of climate change projections for UK river flows

Much research has been carried out on the possible impacts of climate change for UK river flows. Catchment and national-scale studies since the early 1990s are here categorized into four modelling approaches: “top-down” GCM (Global Climate Model)-driven and probabilistic approaches and “bottom-up” stylised and scenario-neutral approaches. Early studies followed a stylised approach with a small number of model experiments focused on system sensitivity. GCM-driven approaches dominate since the mid-1990s and are scenario-led and “top-down”, but which incur the cascade of uncertainty which results in a large amount of information that may not be conducive to decision-making. The emergence of probabilistic projections aims to incorporate probabilistic information in navigating climate model uncertainty but remained “top-down” with challenges over its practical use for water resources planning. The scenario-neutral approach has clear roots in the early stylised approach with the aim to explore plausible futures beyond climate model projections and system sensitivity. A synthesis of studies employing each approach shows that the magnitude and sign of change in different hydrological variables remain uncertain between different regions of the UK. Comparison between studies is difficult due to their methodological differences and consequently different choices along the impact modelling chain, and with a notable geographic bias in catchment selection in southeast England. Major limitations for each approach include barriers to decision-making from wide uncertainty ranges, limited consideration of high-impact outcomes, and challenges in their application in water resources planning. These challenges represent priorities for future research using new “hybrid” approaches to produce complementary information to “top down” projections within a more “bottom-up” framework. Exploratory modelling, robust decision-making and storylines are examples of new approaches that have emerged. Key to the emerging approaches identified is a need to combine different modelling approaches to tackle different sources of uncertainty according to the intended aims of individual applications

SIRT1 catalytic activity has little effect on tumor formation and metastases in a mouse model of breast cancer.

The protein deacetylase SIRT1 has been implicated in the regulation of a large number of cellular processes that are thought to be required for cancer initiation and progression. There are conflicting data that make it unclear whether Sirt1 functions as an oncogene or tumor suppressor. To assess the effect of SIRT1 on the emergence and progression of mammary tumors, we crossed mice that harbor a point mutation that abolishes SIRT1 catalytic activity with mice carrying the polyoma middle T transgene driven by the murine mammary tumor virus promoter (MMTV-PyMT). The absence of SIRT1 catalytic activity neither accelerated nor blocked the formation of tumors and metastases in this model. There was a lag in tumor latency that modestly extended survival in Sirt1 mutant mice that we attribute to a delay in mammary gland development and not to a direct effect of SIRT1 on carcinogenesis. These results are consistent with previous evidence suggesting that Sirt1 is not a tumor promoter or a tumor suppressor