The genome of the blood fluke Schistosoma mansoni

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

Optical and infrared photometry of the Type IInSN1998S: days 11-146

We present contemporaneous optical and infrared (IR) photometric observations of the Type IIn SN 1998S covering the period between 11 and 146 d after discovery. The IR data constitute the first ever IR light curves of a Type IIn supernova. We use blackbody and spline fits to the photometry to examine the luminosity evolution. During the first 2-3 months, the luminosity is dominated by the release of shock-deposited energy in the ejecta. After similar to 100 d the luminosity is powered mostly by the deposition of radioactive decay energy from 0.15 +/-0.05 M-. of Ni-56 which was produced in the explosion. We also report the discovery of an astonishingly high IR excess, K-L'=2.5, that was present at day 130. We interpret this as being due to thermal emission from dust grains in the vicinity of the supernova. We argue that to produce such a high IR luminosity so soon after the explosion, the dust must be pre-existing and so is located in the circumstellar medium of the progenitor. The dust could be heated either by the UV/optical flash (IR echo) or by the X-rays from the interaction of the ejecta with the circumstellar material.

A Burkholderia cenocepacia gene encoding a non-functional tyrosine phosphatase is required for the delayed maturation of the bacteria-containing vacuoles in macrophages

Burkholderia cenocepacia infects patients with cystic fibrosis. We have previously shown that B. cenocepacia can survive in macrophages within membrane vacuoles (BcCVs) that preclude fusion with the lysosome. The bacterial factors involved in B. cenocepacia intracellular survival are not fully elucidated. We report here that deletion of BCAM0628, encoding a predicted low-molecular weight protein tyrosine phosphatase (LMW-PTP) that is restricted to B. cenocepacia strains of the transmissible ET-12 clone, accelerates the maturation of the BcCVs. Compared to parental strain and deletion mutants in other LMW-PTPs that are widely conserved in Burkholderia species, a greater proportion of BcCVs containing the BCAM0628 mutant were targeted to the lysosome. Accelerated BcCV maturation was not due to reduced intracellular viability since BCAM0628 survived and replicated in macrophages similarly to the parental strain. Therefore, BCAM0628 was referred to as dpm (delayed phagosome maturation). We provide evidence that the Dpm protein is secreted during growth in vitro and upon macrophage infection. Dpm secretion requires an N-terminal signal peptide. Heterologous expression of Dpm in B. multivorans confers to this bacterium a similar phagosomal maturation delay as found with B. cenocepacia. We demonstrate that Dpm is an inactive phosphatase, suggesting that its contribution to phagosomal maturation arrest must be unrelated to tyrosine phosphatase activity.

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

Test methods for concrete durability indicators

Durability of concrete structures is primarily dependent on the environmental influences, i.e. the penetration of aggressive substances in the structural element from the environment. Penetrability is an important durability indicator of concrete and by specifying different classes of penetrability of concrete it should be possible to design a structure with the required resistance to environmental loads. This chapter covers descriptions of the available and commonly applied in situ and laboratory, non-invasive and semi-invasive test methods for evaluating concrete penetrability properties.

Application examples of performance-based specification and quality control

This chapter presents an overview on several performance-based approaches for concrete durability specification and conformity assessment of the as-built structure.

Enhancing design space exploration by extending CPU/GPU specifications onto FPGAs

The design cycle for complex special-purpose computing systems is extremely costly and time-consuming. It involves a multiparametric design space exploration for optimization, followed by design verification. Designers of special purpose VLSI implementations often need to explore parameters, such as optimal bitwidth and data representation, through time-consuming Monte Carlo simulations. A prominent example of this simulation-based exploration process is the design of decoders for error correcting systems, such as the Low-Density Parity-Check (LDPC) codes adopted by modern communication standards, which involves thousands of Monte Carlo runs for each design point. Currently, high-performance computing offers a wide set of acceleration options that range from multicore CPUs to Graphics Processing Units (GPUs) and Field Programmable Gate Arrays (FPGAs). The exploitation of diverse target architectures is typically associated with developing multiple code versions, often using distinct programming paradigms. In this context, we evaluate the concept of retargeting a single OpenCL program to multiple platforms, thereby significantly reducing design time. A single OpenCL-based parallel kernel is used without modifications or code tuning on multicore CPUs, GPUs, and FPGAs. We use SOpenCL (Silicon to OpenCL), a tool that automatically converts OpenCL kernels to RTL in order to introduce FPGAs as a potential platform to efficiently execute simulations coded in OpenCL. We use LDPC decoding simulations as a case study. Experimental results were obtained by testing a variety of regular and irregular LDPC codes that range from short/medium (e.g., 8,000 bit) to long length (e.g., 64,800 bit) DVB-S2 codes. We observe that, depending on the design parameters to be simulated, on the dimension and phase of the design, the GPU or FPGA may suit different purposes more conveniently, thus providing different acceleration factors over conventional multicore CPUs.

Burkholderia cenocepacia Lipopolysaccharide Modification and Flagellin Glycosylation Affect Virulence but Not Innate Immune Recognition in Plants

Burkholderia cenocepacia causes opportunistic infections in plants, insects, animals, and humans, suggesting that “virulence” depends on the host and its innate susceptibility to infection. We hypothesized that modifications in key bacterial molecules recognized by the innate immune system modulate host responses to B. cenocepacia. Indeed, modification of lipo- polysaccharide (LPS) with 4-amino-4-deoxy-L-arabinose and flagellin glycosylation attenuates B. cenocepacia infection in Arabi- dopsis thaliana and Galleria mellonella insect larvae. However, B. cenocepacia LPS and flagellin triggered rapid bursts of nitric oxide and reactive oxygen species in A. thaliana leading to activation of the PR-1 defense gene. These responses were drastically reduced in plants with fls2 (flagellin FLS2 host receptor kinase), Atnoa1 (nitric oxide-associated protein 1), and dnd1-1 (reduced production of nitric oxide) null mutations. Together, our results indicate that LPS modification and flagellin glycosylation do not affect recognition by plant receptors but are required for bacteria to establish overt infection.

UV dosimetry for solar water disinfection (SODIS) carried out in different plastic bottles and bags

Solar water disinfection (SODIS) is a well-established inexpensive means of water disinfection in developing countries, but lacks an indicator to illustrate its end-point. A study of the solar UV dosage required for SODIS, in order to achieve a bacteria concentration below the detection limit for: Escherichia coli, Enterococcus spp. and Clostridium perfringens, in water in PET bottles, PE and PE/EVA bags showed disinfection to be most efficient in PE bags, with a solar UV (290–385 nm) dose of 389 kJ m−2 required. In parallel to the disinfection experiments, a range of polyoxometalate, semiconductor photocatalysis and photodegradable dye-based solar UV dosimeter indicators were tested under the same solar UV irradiation conditions. All three types of dosimeter produced indicators that largely and significantly change colour upon exposure to 389 kJ m−2 solar UV; further indicators are reported which change colour at higher doses and hence would be suitable for the less efficient SODIS containers tested. All indicators tested were robust, easy to use and inexpensive so as not to add significantly to the attractive low cost of SODIS. Furthermore, whilst semiconductor photocatalyst and photodegradable dye based indicators are disposable, one-use systems, the polyoxometalate based indicators recover colour in the dark overnight, allowing them to be reused, and hence further decreasing the cost of using indicators during the implementation of the SODIS method.

ArnT proteins that catalyse the glycosylation of lipopolysaccharide share common features with bacterial N-oligosaccharyltransferases

ArnT is a glycosyltransferase that catalyses the addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) to the lipid A moiety of the lipopolysaccharide. This is a critical modification enabling bacteria to resist killing by antimicrobial peptides. ArnT is an integral inner membrane protein consisting of 13 predicted transmembrane helices and a large periplasmic C-terminal domain. We report here the identification of a functional motif with a canonical consensus sequence DEXRYAX(5)MX(3)GXWX(9)YFEKPX(4)W spanning the first periplasmic loop, which is highly conserved in all ArnT proteins examined. Site-directed mutagenesis demonstrated the contribution of this motif in ArnT function, suggesting that these proteins have a common mechanism. We also demonstrate that the Burkholderia cenocepacia and Salmonella enterica serovar Typhimurium ArnT C-terminal domain is required for polymyxin B resistance in vivo. Deletion of the C-terminal domain in B. cenocepacia ArnT resulted in a protein with significantly reduced in vitro binding to a lipid A fluorescent substrate and unable to catalyse lipid A modification with L-Ara4N. An in silico predicted structural model of ArnT strongly resembled the tertiary structure of Campylobacter lari PglB, a bacterial oligosaccharyltransferase involved in protein N-glycosylation. Therefore, distantly related oligosaccharyltransferases from ArnT and PglB families operating on lipid and polypeptide substrates, respectively, share unexpected structural similarity that could not be predicted from direct amino acid sequence comparisons. We propose that lipid A and protein glycosylation enzymes share a conserved catalytic mechanism despite their evolutionary divergence.

Tyrosine phosphorylation and dephosphorylation in Burkholderia cenocepacia affect biofilm formation, growth under nutritional deprivation, and pathogenicity

Burkholderia cenocepacia, a member of the B. cepacia complex (Bcc), is an opportunistic pathogen causing serious chronic infections in patients with cystic fibrosis. Tyrosine phosphorylation has emerged as an important post-translational modification modulating the physiology and pathogenicity of Bcc bacteria. Here, we investigated the predicted bacterial tyrosine kinases BCAM1331 and BceF, and the low molecular weight protein tyrosine phosphatases BCAM0208, BceD and BCAL2200 of B. cenocepacia K56-2. We show that BCAM1331, BceF, BCAM0208 and BceD contributed to biofilm formation, while BCAL2200 was required for growth in nutrient-limited conditions. Multiple deletions of either tyrosine kinase or low molecular weight protein tyrosine phosphatases genes resulted in attenuation of B. cenocepacia intramacrophage survival and reduced pathogenicity in the Galleria mellonella larvae infection model. Experimental evidence indicates that BCAM1331 displays a reduced
tyrosine autophosphorylation activity compared to BceF. Using the artificial substrate p-nitrophenyl phosphate, the phosphatase activity of the three low molecular weight protein tyrosine phosphatases demonstrated similar kinetic parameters. However, only BCAM0208 and BceD could dephosphorylate BceF. Further, BCAL2200 becomes tyrosine phosphorylated in vivo and catalyzes its auto-dephosphorylation. Together, our data suggest that despite having similar biochemical activities low molecular weight protein tyrosine phosphatases and tyrosine kinases have both overlapping and specific roles in the physiology of B. cenocepacia.

Old World megadroughts and pluvials during the Common Era

Climate model projections suggestwidespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era.
The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries
reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability.