Genetic diversity among Escherichia coli O157 : H7 isolates and identification of genes linked to human infections

An Escherichia coli oligonucleotide microarray based on three sequenced genomes was validated for comparative genomic microarray hybridization and used to study the diversity of E. coli O157 isolates from human infections and food and animal sources. Among 26 test strains, 24 (including both Shiga toxin [Stx]-positive and -negative strains) were found to be related to the two sequenced E. coli O157:117 strains, EDL933 and Sakai. However, these strains showed much greater genetic diversity than those reported previously, and most of them could not be categorized as either lineage I or H. Some genes were found more often in isolates from human than from nonhuman sources; e.g., ECs1202 and ECs2976, associated with stx2AB and stx1AB, were in all isolates from human sources but in only 40% of those from nonhuman sources. Some (but not all) lineage I-specific or -dominant genes were also more frequently associated with isolates from human. The results suggested that it might be more effective to concentrate our efforts on finding markers that are directly related to infection rather than those specific to certain lineages. In addition, two Stx-negative O157 cattle isolates (one confirmed to be 117) were significantly different from other Stx-positive and -negative E. coli O157:117 strains and were more similar to MG1655 in their gene content. This work demonstrates that not all E. coli O157:117 strains belong to the same clonal group, and those that were similar to E. coli K-12 might be less virulent.

Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase: findings from a randomised controlled trial

Previously we demonstrated that heparin administration during carotid endarterectomy (CEA) caused a marked, but transient increase in platelet aggregation to arachidonic acid (AA) and adenosine diphosphate (ADP), despite effective platelet cyclo-oxygenase-1 (COX-1) inhibition with aspirin. Here we investigated the metabolism of AA via platelet 12-lipoxygenase (12-LOX) as a possible mediator of the observed transient aspirin resistance, and compared the effects of unfractionated (UFH) and low-molecular-weight (LMWH) heparin. A total of 43 aspirinated patients undergoing CEA were randomised in the trial to 5,000 IU UFH (n=22) or 2,500 IU LMWH (dalteparin, n=21). Platelet aggregation to AA (4x10⁻³) and ADP (3x10⁻⁶) was determined, and the products of the COX-1 and 12-LOX pathways; thromboxane B₂ (TXB₂) and 12-hydroxyeicosatretraenoic acid (12-HETE) were measured in plasma, and in material released from aggregating platelets.Aggregation to AA increased significantly (~10-fold) following heparinisation (p<0.0001), irrespective of heparin type (p=0.33). Significant, but smaller (~2-fold) increases in aggregation to ADP were also seen, which were significantly lower in the platelets of patients randomised to LMWH (p<0.0001). Plasma levels of TxB2 did not rise following heparinisation (p=0.93), but 12-HETE increased significantly in the patients' plasma, and released from platelets stimulated in vitro withADP, with both heparin types (p<0.0001). The magnitude of aggregation to ADP correlated with 12-HETE generation (p=0.03). Heparin administration during CEA generates AA that is metabolised to 12-HETE via the 12-LOX pathway, possibly explaining the phenomenon of transient heparin-induced platelet activation. LMWH has less effect on aggregation and 12-HETE generation than UFH when the platelets are stimulated with ADP.

Therapeutic benefit of low-dose clopidogrel in patients undergoing carotid surgery is linked to variability in the platelet adenosine diphosphate response and patients' weight

BACKGROUND AND PURPOSE: We have previously shown that a single 75-mg tablet of clopidogrel, taken before carotid endarterectomy, significantly reduces postoperative embolization, a marker of thromboembolic stroke. This study explores the antiplatelet effect of this submaximal dose. METHODS: Fifty-six patients on long-term aspirin (150 mg) were randomized to 75 mg clopidogrel or placebo before carotid endarterectomy. Blood samples were taken pre- and postdrug administration and at the end of surgery to measure platelet activation and adenosine diphosphate (ADP) response by flow cytometry and aggregometry. RESULTS: Surgery produced a significant rise in platelet activation in vivo as evidenced by a rise in the percentage of monocyte-platelet aggregates in patients given placebo, but this was not seen in patients receiving clopidogrel. Before surgery, clopidogrel produced a significant reduction in the platelet response to ADP; for example, with 10(-6)M ADP, 77.32+/-2.3% bound fibrinogen in placebo group compared with 67.16+/-3.1% after clopidogrel (P=0.01). This was accentuated after surgery when the percentage of platelets binding fibrinogen in response to ADP was 76.53+/-2.2% in patients given placebo and 62.84+/-3.3% in the clopidogrel group (P=0.002). Similar differences were seen over a range of ADP concentrations and by aggregometry. Platelet responsiveness before treatment was highly variable and was positively correlated with the inhibitory effect of clopidogrel; patients with the highest baseline response to ADP showed the greatest response to clopidogrel. A negative correlation was seen between the effect of clopidogrel and patients' weight (r=0.57; P=0.002). CONCLUSIONS: These results explain how a single 75-mg dose of clopidogrel produces a significant clinical impact on embolization.

Opening up climate research: A linked data approach to publishing data provenance

Traditionally, the formal scientific output in most fields of natural science has been limited to peer- reviewed academic journal publications, with less attention paid to the chain of intermediate data results and their associated metadata, including provenance. In effect, this has constrained the representation and verification of the data provenance to the confines of the related publications. Detailed knowledge of a dataset’s provenance is essential to establish the pedigree of the data for its effective re-use, and to avoid redundant re-enactment of the experiment or computation involved. It is increasingly important for open-access data to determine their authenticity and quality, especially considering the growing volumes of datasets appearing in the public domain. To address these issues, we present an approach that combines the Digital Object Identifier (DOI) – a widely adopted citation technique – with existing, widely adopted climate science data standards to formally publish detailed provenance of a climate research dataset as an associated scientific workflow. This is integrated with linked-data compliant data re-use standards (e.g. OAI-ORE) to enable a seamless link between a publication and the complete trail of lineage of the corresponding dataset, including the dataset itself.

Synthesis of linked heterocycles via use of bis-acetylenic compounds

Linked bis-pyrazoles, a pyrazolyl-isoxazole, a pyrazolyl-pyrimidine and a pyrazolyl-triazole were synthesized starting with commercially available 1,4-bis(trimethylsilyl)-1,3-butadiyne 1 or readily available bis-acetylenic diketone 22. A stepwise approach based on the use of 1 allowed the synthesis of nonsymmetrically substituted bis-pyrazoles and linked heterocycles with two different cores whereas a symmetric approach based on the use of 22 allowed a very short synthesis of symmetric bis-pyrazoles.

Geophysical characterization of the complex dynamics of groundwater and seawater exchange in a highly stressed aquifer system linked to a coastal lagoon (SE Spain)

Anthropogenic pressure influences the two-way interactions between shallow aquifers and coastal lagoons. Aquifer overexploitation may lead to seawater intrusion, and aquifer recharge from rainfall plus irrigation may, in turn, increase the groundwater discharge into the lagoon. We analyse the evolution, since the 1950s up to the present, of the interactions between the Campo de Cartagena Quaternary aquifer and the Mar Menor coastal lagoon (SE Spain). This is a very heterogeneous and anisotropic detrital aquifer, where aquifer–lagoon interface has a very irregular geometry. Using electrical resistivity tomography, we clearly identified the freshwater–saltwater transition zone and detected areas affected by seawater intrusion. Severity of the intrusion was spatially variable and significantly related to the density of irrigation wells in 1950s–1960s, suggesting the role of groundwater overexploitation. We distinguish two different mechanisms by which water from the sea invades the land: (a) horizontal advance of the interface due to a wide exploitation area and (b) vertical rise (upconing) caused by local intensive pumping. In general, shallow parts of the geophysical profiles show higher electrical resistivity associated with freshwater mainly coming from irrigation return flows, with water resources mostly from deep confined aquifers and imported from Tagus river, 400 km north. This indicates a likely reversal of the former seawater intrusion process.

Integrin-linked kinase regulates the rate of platelet activation and is essential for the formation of stable thrombi

BACKGROUND: Integrin-linked kinase (ILK) and its associated complex of proteins are involved in many cellular activation processes, including cell adhesion and integrin signaling. We have previously demonstrated that mice with induced platelet ILK deficiency show reduced platelet activation and aggregation, but only a minor bleeding defect. Here, we explore this apparent disparity between the cellular and hemostatic phenotypes. METHODS: The impact of ILK inhibition on integrin αII b β3 activation and degranulation was assessed with the ILK-specific inhibitor QLT0267, and a conditional ILK-deficient mouse model was used to assess the impact of ILK deficiency on in vivo platelet aggregation and thrombus formation. RESULTS: Inhibition of ILK reduced the rate of both fibrinogen binding and α-granule secretion, but was accompanied by only a moderate reduction in the maximum extent of platelet activation or aggregation in vitro. The reduction in the rate of fibrinogen binding occurred prior to degranulation or translocation of αII b β3 to the platelet surface. The change in the rate of platelet activation in the absence of functional ILK led to a reduction in platelet aggregation in vivo, but did not change the size of thrombi formed following laser injury of the cremaster arteriole wall in ILK-deficient mice. It did, however, result in a marked decrease in the stability of thrombi formed in ILK-deficient mice. CONCLUSION: Taken together, the findings of this study indicate that, although ILK is not essential for platelet activation, it plays a critical role in facilitating rapid platelet activation, which is essential for stable thrombus formation.

The MELODIES project: integrating diverse data using Linked Data and cloud computing

We present an overview of the MELODIES project, which is developing new data-intensive environmental services based on data from Earth Observation satellites, government databases, national and European agencies and more. We focus here on the capabilities and benefits of the project’s “technical platform”, which applies cloud computing and Linked Data technologies to enable the development of these services, providing flexibility and scalability.

Atmospheric response in summer linked to recent Arctic sea ice loss

Since 2007 a large decline in Arctic sea ice has been observed. The large-scale atmospheric circulation response to this decline is investigated in ERA-Interim reanalyses and HadGEM3 climate model experiments. In winter, post-2007 observed circulation anomalies over the Arctic, North Atlantic and Eurasia are small compared to interannual variability. In summer, the post-2007 observed circulation is dominated by an anticyclonic anomaly over Greenland which has a large signal-to-noise ratio. Climate model experiments driven by observed SST and sea ice anomalies are able to capture the summertime pattern of observed circulation anomalies, although the magnitude is a third of that observed. The experiments suggest high SSTs and reduced sea ice in the Labrador Sea lead to positive temperature anomalies in the lower troposphere which weaken the westerlies over North America through thermal wind balance. The experiments also capture cyclonic anomalies over Northwest Europe, which are consistent with downstream Rossby wave propagation

Tensor regression based on linked multiway parameter analysis

Classical regression methods take vectors as covariates and estimate the corresponding vectors of regression parameters. When addressing regression problems on covariates of more complex form such as multi-dimensional arrays (i.e. tensors), traditional computational models can be severely compromised by ultrahigh dimensionality as well as complex structure. By exploiting the special structure of tensor covariates, the tensor regression model provides a promising solution to reduce the model’s dimensionality to a manageable level, thus leading to efficient estimation. Most of the existing tensor-based methods independently estimate each individual regression problem based on tensor decomposition which allows the simultaneous projections of an input tensor to more than one direction along each mode. As a matter of fact, multi-dimensional data are collected under the same or very similar conditions, so that data share some common latent components but can also have their own independent parameters for each regression task. Therefore, it is beneficial to analyse regression parameters among all the regressions in a linked way. In this paper, we propose a tensor regression model based on Tucker Decomposition, which identifies not only the common components of parameters across all the regression tasks, but also independent factors contributing to each particular regression task simultaneously. Under this paradigm, the number of independent parameters along each mode is constrained by a sparsity-preserving regulariser. Linked multiway parameter analysis and sparsity modeling further reduce the total number of parameters, with lower memory cost than their tensor-based counterparts. The effectiveness of the new method is demonstrated on real data sets.

Southern Hemisphere jet latitude biases in CMIP5 models linked to shortwave cloud forcing

Substantial biases in shortwave cloud forcing (SWCF) of up to ±30 W m−2are found in the midlatitudes of the Southern Hemisphere in the historical simulations of 34 CMIP5 coupled general circulation models. The SWCF biases are shown to induce surface temperature anomalies localized in the midlatitudes, and are significantly correlated with the mean latitude of the eddy-driven jet, with a negative SWCF bias corresponding to an equatorward jet latitude bias. Aquaplanet model experiments are performed to demonstrate that the jet latitude biases are primarily induced by the midlatitude SWCF anomalies, such that the jet moves toward (away from) regions of enhanced (reduced) temperature gradients. The results underline the necessity of accurately representing cloud radiative forcings in state-of-the-art coupled models.

Task relevance of emotional information affects anxiety-linked attention bias in visual search

Task relevance affects emotional attention in healthy individuals. Here, we investigate whether the association between anxiety and attention bias is affected by the task relevance of emotion during an attention task. Participants completed two visual search tasks. In the emotion-irrelevant task, participants were asked to indicate whether a discrepant face in a crowd of neutral, middle-aged faces was old or young. Irrelevant to the task, target faces displayed angry, happy, or neutral expressions. In the emotion-relevant task, participants were asked to indicate whether a discrepant face in a crowd of middle-aged neutral faces was happy or angry (target faces also varied in age). Trait anxiety was not associated with attention in the emotion-relevant task. However, in the emotion-irrelevant task, trait anxiety was associated with a bias for angry over happy faces. These findings demonstrate that the task relevance of emotional information affects conclusions about the presence of an anxiety-linked attention bias.

High-throughput phenotyping (HTP) identifies seedling root traits linked to variation in seed yield and nutrient capture in field-grown oilseed rape (Brassica napusL.)

Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a ‘pouch and wick’ HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR.