Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans.

Context. Near-Earth asteroid 162173 (1999 JU3) is a potential flyby and rendezvous target for interplanetary missions because of its easy-to-reach orbit. The physical and thermal properties of the asteroid are relevant for establishing the scientific mission goals and also important in the context of near-Earth object studies in general. Aims. Our goal was to derive key physical parameters such as shape, spin-vector, size, geometric albedo, and surface properties of 162173 (1999 JU3). Methods. With three sets of published thermal observations (ground-based N-band, Akari IRC, Spitzer IRS), we applied a thermophysical model to derive the radiometric properties of the asteroid. The calculations were performed for the full range of possible shape and spin-vector solutions derived from the available sample of visual lightcurve observations. Results. The near-Earth asteroid 162173 (1999 JU3) has an effective diameter of 0.87 ± 0.03 km and a geometric albedo of 0.070 ± 0.006. The χ 2 -test reveals a strong preference for a retrograde sense of rotation with a spin-axis orientation of λ ecl = 73 • , β ecl = −62 • and P sid = 7.63 ± 0.01 h. The most likely thermal inertia ranges between 200 and 600 J m −2 s −0.5 K −1 , about a factor of 2 lower than the value for 25143 Itokawa. This indicates that the surface lies somewhere between a thick-dust regolith and a rock/boulder/cm-sized, gravel-dominated surface like that of 25143 Itokawa. Our analysis represents the first time that shape and spin-vector information has been derived from a combined data set of visual lightcurves (reflected light) and mid-infrared photometry and spectroscopy (thermal emission).

Using a high-throughput pyrosequencing technology, this study assessed bacterial community structure and time-scale variability in great detail in seven full-scale anaerobic digesters operated variously in terms of influent substrate, digestion temperature, and reactor configuration. Pyrosequencing generated a total of 83,774 sequence reads from 40 digester sludge samples collected monthly for six months. The highest number of sequence reads were detected within Proteobacteria (20.5%), followed by those within Bacteroidetes (19.7%), Firmicutes (17.8%), and Chloroflexi (4.8%). The relative composition of bacterial populations was varied within the digesters as well as between the digesters, and the bacterial community structures were mainly influenced by digestion temperature. Detailed bacterial community structures were assessed by analyzing the operational taxonomic units (OTUs) based on 97% sequence similarity, which resulted in a total of 9051 OTUs. Among these, a total of 31 core OTUs were analyzed and inferred phylogenetically, which enabled us to classify the sequences within an unclassified phylum. Unclassified sequences were mostly affiliated with the sequences within Spirochaetes and Firmicutes. Interestingly, numerically dominant novel phylotypes (18% of the total sequence reads) presumably involved in anaerobic digestion within Spirochaetes were identified. Temporal variability was further explored using a non-metric multidimensional scaling ordination which demonstrated that the variability of the bacterial community within the digesters was smaller than between digesters. Correlation analysis demonstrated that digester performance and operational conditions affected the pattern of bacterial community in the ordination. Additionally, a multi-response permutation procedure revealed that the bacterial communities within the digesters were more similar than those belonging to other digesters statistically, demonstrating a patchiness of the digesters in the distribution of bacterial populations. Overall, this study revealed the correlation of bacterial community structure and time-scale variability with digester performance and operating conditions.

Ongoing elimination efforts have altered the global distribution of Onchocerca volvulus, the agent of river blindness, and further population restructuring is expected as efforts continue. Therefore, a better understanding of population-genetic processes and their effect on biogeography is needed to support elimination goals. We describe O. volvulus genome variation in 27 isolates from early 1990s (before widespread mass treatment) from four distinct locales: Ecuador, Uganda, the West African forest, and the West African savanna. We observed genetic substructuring between Ecuador and West Africa and between the West African forest and savanna bioclimes, with evidence of unidirectional gene flow from savanna to forest strains. We identified forest:savanna-discriminatory genomic regions and report a set of ancestry informative loci that can be used to differentiate between forest, savanna and admixed isolates, which has not previously been possible. We observed mito-nuclear discordance possibly stemming from incomplete lineage sorting. The catalog of the nuclear, mitochondrial and endosymbiont DNA variants generated in this study will support future basic and translational onchocerciasis research, with particular relevance for ongoing control programs and boost efforts to characterize drug, vaccine, and diagnostic targets.

ABSTRACT. On 2005 December 30, Y.-J. Choi and P. R. Weissman discovered that the formerly dormant Centaur 2000 EC98 was in strong outburst. Previous observations by P. Rousselot et al. spanning a 3-year period indicated a lack of coma down to the 27 mag arcsec À2 level. We present Spitzer Space Telescope MIPS observations of this newly active Centaur-now known as 174P/Echeclus (2000 EC98)-or 60558 Echeclus-taken in 2006 late February. The images show strong signal at both the 24 and 70 μm bands and reveal an extended coma about 2′ in diameter. Analyses yield estimates of the coma signal contribution that are in excess of 90% of the total signal in the 24 μm band. Dust production estimates ranging from 1:7-4 × 10 2 kg s À1 are on the order of 30 times that seen in other Centaurs. Simultaneous visible-wavelength observations were also obtained with Palomar Observatory's 200-inch telescope, the 1.8-m Vatican Advanced Technology Telescope, the Bohyunsan Optical Astronomy Observatory (BOAO) 1.8-m telescope, and Table Mountain Observatory's 0.6-m telescope, revealing a coma morphology nearly identical to the mid-IR observations. The grain size distribution derived from the data yields a log particle mass power-law with slope parameter α ¼ À0:87 AE 0:07, and is consistent with steady cometary activity, such as that observed during the Stardust spacecraft's encounter at 81P/Wild 2, and not with an impactdriven event, such as that caused by the Deep Impact experiment.

No abstract

Helminth.net (http://www.helminth.net) is the new moniker for a collection of databases: Nematode.net and Trematode.net. Within this collection we provide services and resources for parasitic roundworms (nematodes) and flatworms (trematodes), collectively known as helminths. For over a decade we have provided resources for studying nematodes via our veteran site Nematode.net (http://nematode.net). In this article, (i) we provide an update on the expansions of Nematode.net that hosts omics data from 84 species and provides advanced search tools to the broad scientific community so that data can be mined in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site dedicated to the dissemination of data from flukes, flatworm parasites of the class Trematoda, phylum Platyhelminthes. Trematode.net is an independent component of Helminth.net and currently hosts data from 16 species, with information ranging from genomic, functional genomic data, enzymatic pathway utilization to microbiome changes associated with helminth infections. The databases’ interface, with a sophisticated query engine as a backbone, is intended to allow users to search for multi-factorial combinations of species’ omics properties. This report describes updates to Nematode.net since its last description in NAR, 2012, and also introduces and presents its new sibling site, Trematode.net.

Human pluripotent stem cell-derived hepatocytes have the potential to provide in vitro model systems for drug discovery and hepatotoxicity testing. However, these cells are currently unsuitable for drug toxicity and efficacy testing because of their limited expression of genes encoding drug-metabolizing enzymes, especially cytochrome P450 (CYP) enzymes. Transcript levels of major CYP genes were much lower in human embryonic stem cell-derived hepatocytes (hESC-Hep) than in human primary hepatocytes (hPH). To verify the mechanism underlying this reduced expression of CYP genes, including CYP1A1, CYP1A2, CYP1B1, CYP2D6, and CYP2E1, we investigated their epigenetic regulation in terms of DNA methylation and histone modifications in hESC-Hep and hPH. CpG islands of CYP genes were hypermethylated in hESC-Hep, whereas they had an open chromatin structure, as represented by hypomethylation of CpG sites and permissive histone modifications, in hPH. Inhibition of DNA methyltransferases (DNMTs) during hepatic maturation induced demethylation of the CpG sites of CYP1A1 and CYP1A2, leading to the up-regulation of their transcription. Combinatorial inhibition of DNMTs and histone deacetylases (HDACs) increased the transcript levels of CYP1A1, CYP1A2, CYP1B1, and CYP2D6. Our findings suggest that limited expression of CYP genes in hESC-Hep is modulated by epigenetic regulatory factors such as DNMTs and HDACs.