Automatic prediction of functional site regions in low-resolution protein structures

World-wide structural genomics initiatives are rapidly accumulating structures for which limited functional information is available. Additionally, state-of-the art structural prediction programs are now capable of generating at least low resolution structural models of target proteins. Accurate detection and classification of functional sites within both solved and modelled protein structures therefore represents an important challenge. We present a fully automatic site detection method, FuncSite, that uses neural network classifiers to predict the location and type of functionally important sites in protein structures. The method is designed primarily to require only backbone residue positions without the need for specific side-chain atoms to be present. In order to highlight effective site detection in low resolution structural models FuncSite was used to screen model proteins generated using mGenTHREADER on a set of newly released structures. We found effective metal site detection even for moderate quality protein models illustrating the robustness of the method.

The nature of Arctic polar vortices in chemistry-climate models

The structure of the Arctic stratospheric polar vortex in three chemistry–climate models (CCMs) taken from the CCMVal-2 intercomparison is examined using zonal mean and geometric-based methods. The geometric methods are employed by taking 2D moments of potential vorticity fields that are representative of the polar vortices in each of the models. This allows the vortex area, centroid location and ellipticity to be determined, as well as a measure of vortex filamentation. The first part of the study uses these diagnostics to examine how well the mean state, variability and extreme variability of the polar vortices are represented in CCMs compared to ERA-40 reanalysis data, and in particular for the UMUKCA-METO, NIWA-SOCOL and CCSR/NIES models. The second part of the study assesses how the vortices are predicted to change in terms of the frequency of sudden stratospheric warmings and their general structure over the period 1960–2100. In general, it is found that the vortices are climatologically too far poleward in the CCMs and produce too few large-scale filamentation events. Only a small increase is observed in the frequency of sudden stratospheric warming events from the mean of the CCMVal-2 models, but the distribution of extreme variability throughout the winter period is shown to change towards the end of the twentyfirst century.

The impact of 21st century Arctic sea ice decline on the climate and mass balance of the Greenland ice sheet and Svalbard’s glaciers and ice caps

The Arctic is a region particularly susceptible to rapid climate change. General circulation models (GCMs) suggest a polar amplification of any global warming signal by a factor of about 1.5 due, in part, to sea ice feedbacks. The dramatic recent decline in multi-year sea ice cover lies outside the standard deviation of the CMIP3 ensemble GCM predictions. Sea ice acts as a barrier between cold air and warmer oceans during winter, as well as inhibiting evaporation from the ocean surface water during the summer. An ice free Arctic would likely have an altered hydrological cycle with more evaporation from the ocean surface leading to changes in precipitation distribution and amount. Using the U.K. Met Office Regional Climate Model (RCM), HadRM3, the atmospheric effects of the observed and projected reduction in Arctic sea ice are investigated. The RCM is driven by the atmospheric GCM HadAM3. Both models are forced with sea surface temperature and sea ice for the period 2061-2090 from the CMIP3 HadGEM1 experiments. Here we use an RCM at 50km resolution over the Arctic and 25km over Svalbard, which captures well the present-day pattern of precipitation and provides a detailed picture of the projected changes in the behaviour of the oceanic-atmosphere moisture fluxes and how they affect precipitation. These experiments show that the projected 21stCentury sea ice decline alone causes large impacts to the surface mass balance (SMB) on Svalbard. However Greenland’s SMB is not significantly affected by sea ice decline alone, but responds with a strongly negative shift in SMB when changes to SST are incorporated into the experiments. This is the first study to characterise the impact of changes in future sea ice to Arctic terrestrial cryosphere mass balance.

Physical interpretation of the spectral radiative signature in the transition zone between cloud-free and cloudy regions

One-second-resolution zenith radiance measure- ments from the Atmospheric Radiation Measurement pro- gram’s new shortwave spectrometer (SWS) provide a unique opportunity to analyze the transition zone between cloudy and cloud-free air, which has considerable bearing on the aerosol indirect effect. In the transition zone, we find a re- markable linear relationship between the sum and difference of radiances at 870 and 1640 nm wavelengths. The intercept of the relationship is determined primarily by aerosol prop- erties, and the slope by cloud properties. We then show that this linearity can be predicted from simple theoretical con- siderations and furthermore that it supports the hypothesis of inhomogeneous mixing, whereby optical depth increases as a cloud is approached but the effective drop size remains un- changed.

Optical genetic mapping defines regions of chromosomal variation in serovars of S. enterica subsp enterica of concern for human and animal health

Infections involving Salmonella enterica subsp. enterica serovars have serious animal and human health implications; causing gastroenteritis in humans and clinical symptoms, such as diarrhoea and abortion, in livestock. In this study an optical genetic mapping technique was used to screen 20 field isolate strains from four serovars implicated in disease outbreaks. The technique was able to distinguish between the serovars and the available sequenced strains and group them in agreement with similar data from microarrays and PFGE. The optical maps revealed variation in genome maps associated with antimicrobial resistance and prophage content in S. Typhimurium, and separated the S. Newport strains into two clear geographical lineages defined by the presence of prophage sequences. The technique was also able to detect novel insertions that may have had effects on the central metabolism of some strains. Overall optical mapping allowed a greater level of differentiation of genomic content and spatial information than more traditional typing methods.

Epidemic multidrug-resistant (MDR-AmpC) Salmonella enterica serovar Newport strains contain three phage regions and a MDR resistance plasmid

Multidrug-resistant (MDR-AmpC) Salmonella enterica serovar Newport has caused serious disease in animals and humans in North America, whereas in the UK S. enterica serovar Newport is not associated with severe disease and usually sensitive to antibiotics; MDR S. Newport (not AmpC) strains have only been isolated from poultry. We found that UK poultry strains belonged to MLST type ST166 and were distinct from cattle isolates for being able to utilize D-tagotose and when compared by pulsed-field gel electrophoresis (PFGE), comparative genomic hybridization (CGH) and diversity arrays technology (DArT). Cattle strains belonged to the ST45 complex differing from ST166 at all seven loci. PFGE showed that 19 out of 27 cattle isolates were more than 85% similar to each other and some UK and US strains were indistinguishable. Both CGH and DArT identified genes (including phage-related ones) that were uniquely present in the US isolates and two such genes identified by DArT showed sequence similarities with the pertussis-like (artAB) toxin. This work demonstrates that MDR-AmpC S. Newport from the USA are genetically closely related to pan-susceptible strains from the UK, but contained three extra phage regions and a MDR plasmid.

Sources of multi-decadal variability in Arctic sea ice extent

The observed dramatic decrease in September sea ice extent (SIE) has been widely discussed in the scientific literature. Though there is qualitative agreement between observations and ensemble members of the Third Coupled Model Intercomparison Project (CMIP3), it is concerning that the observed trend (1979–2010) is not captured by any ensemble member. The potential sources of this discrepancy include: observational uncertainty, physical model limitations and vigorous natural climate variability. The latter has received less attention and is difficult to assess using the relatively short observational sea ice records. In this study multi-centennial pre-industrial control simulations with five CMIP3 climate models are used to investigate the role that the Arctic oscillation (AO), the Atlantic multi-decadal oscillation (AMO) and the Atlantic meridional overturning circulation (AMOC) play in decadal sea ice variability. Further, we use the models to determine the impact that these sources of variability have had on SIE over both the era of satellite observation (1979–2010) and an extended observational record (1953–2010). There is little evidence of a relationship between the AO and SIE in the models. However, we find that both the AMO and AMOC indices are significantly correlated with SIE in all the models considered. Using sensitivity statistics derived from the models, assuming a linear relationship, we attribute 0.5–3.1%/decade of the 10.1%/decade decline in September SIE (1979–2010) to AMO driven variability.

Immune factors and fatty acid composition in human milk from river/lake, coastal and inland regions of China

Breast milk fatty acid composition may be affected by maternal diet during gestation and lactation. The influence of dietary and breast milk fatty acids on breast milk immune factors is poorly defined. We determined the fatty acid composition and immune factor concentrations of breast milk from women residing in river & lake, coastal, and inland regions of China, which differ in their consumption of lean fish and oily fish. Breast milk samples were collected on days 3 to 5 (colostrum), 14 and 28 post-partum and analysed for soluble CD14 (sCD14), transforming growth factor (TGF)-β1, TGF-β2, secretory immunoglobulin A (sIgA) and fatty acids. The fatty acid composition of breast milk differed between regions and with time post-partum. The concentrations of all four immune factors in breast milk decreased over time, with sCD14, sIgA and TGF-β1 being highest in colostrum in the river & lake region. Breast milk DHA and arachidonic acid (AA) were positively associated, and γ-linolenic acid and EPA negatively associated, with the concentrations of each of the four immune factors. In conclusion, breast milk fatty acids and immune factors differ between regions in China characterised by different patterns of fish consumption and change during the course of lactation. A higher breast milk DHA and AA concentration is associated with higher concentrations of immune factors in breast milk, suggesting a role for these fatty acids in promoting gastrointestinal and immune maturation of the infant.

Arctic Oscillation and Antarctic Oscillation in internal atmospheric variability

n this study, we investigated the features of Arctic Oscillation (AO) and Antarctic Oscillation (AAO), that is, the annular modes in the extratropics, in the internal atmospheric variability attained through an ensemble of integrations by an atmospheric general circulation model (AGCM) forced with the global observed SSTs. We focused on the interannual variability of AO/AAO, which is dominated by internal atmospheric variability. In comparison with previous observed results, the AO/AAO in internal atmospheric variability bear some similar characteristics, but exhibit a much clearer spatial structure: significant correlation between the North Pacific and North Atlantic centers of action, much stronger and more significant associated precipitation anomalies, and the meridional displacement of upper-tropospheric westerly jet streams in the Northern/Southern Hemisphere. In addition, we examined the relationship between the North Atlantic Oscillation (NAO)/AO and East Asian winter monsoon (EAWM). It has been shown that in the internal atmospheric variability, the EAWM variation is significantly related to the NAO through upper-tropospheric atmospheric teleconnection patterns.

The monitoring of ecological quality and the classification of standing waters in temperate regions: a review and proposal based on a worked scheme for British waters

This paper reviews the ways that quality can be assessed in standing waters, a subject that has hitherto attracted little attention but which is now a legal requirement in Europe. It describes a scheme for the assessment and monitoring of water and ecological quality in standing waters greater than about I ha in area in England & Wales although it is generally relevant to North-west Europe. Thirteen hydrological, chemical and biological variables are used to characterise the standing water body in any current sampling. These are lake volume, maximum depth, onductivity, Secchi disc transparency, pH, total alkalinity, calcium ion concentration, total N concentration,winter total oxidised inorganic nitrogen (effectively nitrate) concentration, total P concentration, potential maximum chlorophyll a concentration, a score based on the nature of the submerged and emergent plant community, and the presence or absence of a fish community. Inter alia these variables are key indicators of the state of eutrophication, acidification, salinisation and infilling of a water body.

Binding properties and adhesion-mediating regions of the major sheath protein of Treponema denticola ATCC 35405

There is growing evidence that a number of oral Treponema species, in particular Treponema denticola, are associated with the progression of human periodontal disease. The major sheath (or surface) protein (Msp) of T. denticola is implicated in adhesion of bacteria to host cells and tissue proteins and is likely to be an important virulence factor. However, the binding regions of the Msp are not known. We have purified from Escherichia coli recombinant Msp (rMsp) polypeptides corresponding to the following: full-length Msp (rMsp) minus 13 N-terminal amino acid (aa) residues, an amino-terminal fragment (rN-Msp, 189 aa residues), a 57-aa residue segment from the central region (rV-Msp), and a C-terminal fragment (rC-Msp, 272 aa residues). rMsp (530 aa residues) bound to immobilized fibronectin, keratin, laminin, collagen type 1, fibrinogen, hyaluronic acid, and heparin. The N- and V-region polypeptides, but not rC-Msp, also bound to these substrates. Binding of rMsp to fibronectin was targeted to the N-terminal heparin I/fibrin I domain. Antibodies to the N-region or V-region polypeptides, but not antibodies to the rC-Msp fragment, blocked adhesion of T. denticola ATCC 35405 cells to a range of host protein molecules. These results suggest that the N-terminal half of Msp carries epitopes that are surface exposed and that are involved in mediating adhesion. Binding of rMsp onto the cell surface of low-level fibronectin-binding Treponema isolates conferred a 10-fold increase in fibronectin binding. This confirms that Msp functions autonomously as an adhesin and raises the possibility that phenotypic complementation of virulence functions might occur within mixed populations of Treponema species.

Global and regional temperature-change potentials for near-term climate forcers

We examine the climate effects of the emissions of near-term climate forcers (NTCFs) from 4 continental regions (East Asia, Europe, North America and South Asia) using radiative forcing from the task force on hemispheric transport of air pollution source-receptor global chemical transport model simulations. These simulations model the transport of 3 aerosol species (sulphate, particulate organic matter and black carbon) and 4 ozone precursors (methane, nitric oxides (NOx), volatile organic compounds and carbon monoxide). From the equilibrium radiative forcing results we calculate global climate metrics, global warming potentials (GWPs) and global temperature change potentials (GTPs) and show how these depend on emission region, and can vary as functions of time. For the aerosol species, the GWP(100) values are −37±12, −46±20, and 350±200 for SO2, POM and BC respectively for the direct effects only. The corresponding GTP(100) values are −5.2±2.4, −6.5±3.5, and 50±33. This analysis is further extended by examining the temperature-change impacts in 4 latitude bands. This shows that the latitudinal pattern of the temperature response to emissions of the NTCFs does not directly follow the pattern of the diagnosed radiative forcing. For instance temperatures in the Arctic latitudes are particularly sensitive to NTCF emissions in the northern mid-latitudes. At the 100-yr time horizon the ARTPs show NOx emissions can have a warming effect in the northern mid and high latitudes, but cooling in the tropics and Southern Hemisphere. The northern mid-latitude temperature response to northern mid-latitude emissions of most NTCFs is approximately twice as large as would be implied by the global average.