Genome-wide analysis of the response to ivermectin treatment by a Swedish field population of Haemonchus contortus

Haemonchus contortus is a pathogenic gastrointestinal nematode of small ruminants and, in part due to its capacity to develop resistance to drugs, contributes to significant losses in the animal production sector worldwide. Despite decades of research, comparatively little is known about the specific mechanism(s) driving resistance to drugs such as ivermectin in this species. Here we describe a genome-wide approach to detect evidence of selection by ivermectin treatment in a field population of H. contortus from Sweden, using parasites sampled from the same animals before and seven days after ivermectin exposure followed by whole-genome sequencing. Despite an 89% reduction in parasites recovered after treatment measured by the fecal egg count reduction test, the surviving population was highly genetically similar to the population before treatment, suggesting that resistance has likely evolved over time and that resistance alleles are present on diverse haplotypes. Pairwise gene and SNP frequency comparisons indicated the highest degree of differentiation was found at the terminal end of chromosome 4, whereas the most striking difference in nucleotide diversity was observed in a region on chromosome 5 previously reported to harbor a major quantitative trait locus involved in ivermectin resistance. These data provide novel insight into the genome-wide effect of ivermectin selection in a field population as well as confirm the importance of the previously established quantitative trait locus in the development of resistance to ivermectin

Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

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

X-Ray Evidence for Flare Density Variations and Continual Chromospheric Evaporation in Proxima Centauri

Using the XMM-Newton X-ray observatory to monitor the nearest star to the Sun, Proxima Centauri, we recorded the weakest X-ray flares on a magnetically active star ever observed. Correlated X-ray and optical variability provide strong support for coronal energy and mass supply by a nearly continuous sequence of rapid explosive energy releases. Variable emission line fluxes were observed in the He-like triplets of OVII and NeIX during a giant flare. They give direct X-ray evidence for density variations, implying densities between 2x10^{10} - 4x10^{11} cm^{-3} and providing estimates of the mass and the volume of the line-emitting plasma. We discuss the data in the context of the chromospheric evaporation scenario.Comment: 10 pages, 2 figures, accepted by The Astrophysical Journal, Letters; improved calculations of radiative loss of cool plasma (toward end of paper

Legitimacy in conflict: concepts, practices, challenges

The study of legitimacy in situations of conflict and peacebuilding has increased in recent years. However, current work on the topic adopts many assumptions, definitions, and understandings from classical legitimacy theory, which centers on the relationship between the nation-state and its citizens. In this introduction, we provide a detailed critical overview of current theories of legitimacy and legitimation and demonstrate why they have only limited applicability in conflict and post-conflict contexts, focusing on the three main areas that the articles included in this special issue examine: audiences for legitimacy, sources of legitimacy, and legitimation. In particular, we show how conflict and post-conflict contexts are marked by the fragmentation and personalization of power; the proliferation and fragmentation of legitimacy audiences; and ambiguity surrounding legitimation strategies

Optical Light Curve of the Type Ia Supernova 1998bu in M96 and the Supernova Calibration of the Hubble Constant

We present the UBVRI light curves of the Type Ia supernova SN 1998bu which appeared in the nearby galaxy M96 (NGC 3368). M96 is a spiral galaxy in the Leo I group which has a Cepheid-based distance. Our photometry allows us to calculate the absolute magnitude and reddening of this supernova. These data, when combined with measurements of the four other well-observed supernovae with Cepheid based distances, allow us to calculate the Hubble constant with respect to the Hubble flow defined by the distant Calan/Tololo Type Ia sample. We find a Hubble constant of 64.0 +/- 2.2(internal) +/- 3.5(external) km/s/Mpc, consistent with most previous estimates based on Type Ia supernovae. We note that the two well-observed Type Ia supernovae in Fornax, if placed at the Cepheid distance to the possible Fornax spiral NGC 1365, are apparently too faint with respect to the Calan/Tololo sample calibrated with the five Type Ia supernovae with Cepheid distances to the host galaxies.Comment: AAS LaTeX, 20 pages, 4 figures, 6 tables, accepted for publication in the Astronomical Journal. Figure 1 (finding chart) not include

Complete representation of a tapeworm genome reveals chromosomes capped by centromeres, necessitating a dual role in segregation and protection

Background: Chromosome-level assemblies are indispensable for accurate gene prediction, synteny assessment, and understanding higher-order genome architecture. Reference and draft genomes of key helminth species have been published, but little is yet known about the biology of their chromosomes. Here, we present the complete genome of the tapeworm Hymenolepis microstoma, providing a reference quality, end-to-end assembly that represents the first fully assembled genome of a spiralian/lophotrochozoan, revealing new insights into chromosome evolution. Results: Long-read sequencing and optical mapping data were added to previous short-read data enabling complete re-assembly into six chromosomes, consistent with karyology. Small genome size (169 Mb) and lack of haploid variation (1 SNP/3.2 Mb) contributed to exceptionally high contiguity with only 85 gaps remaining in regions of low complexity sequence. Resolution of repeat regions reveals novel gene expansions, micro-exon genes, and spliced leader trans-splicing, and illuminates the landscape of transposable elements, explaining observed length differences in sister chromatids. Syntenic comparison with other parasitic flatworms shows conserved ancestral linkage groups indicating that the H. microstoma karyotype evolved through fusion events. Strikingly, the assembly reveals that the chromosomes terminate in centromeric arrays, indicating that these motifs play a role not only in segregation, but also in protecting the linear integrity and full lengths of chromosomes. Conclusions: Despite strong conservation of canonical telomeres, our results show that they can be substituted by more complex, species-specific sequences, as represented by centromeres. The assembly provides a robust platform for investigations that require complete genome representation

Nonthermal Hard X-ray Emission and Iron Kalpha Emission from a Superflare on II Pegasi

We report on an X-ray flare detected on the active binary system II~Pegasi with the Swift telescope. The trigger had a 10-200 keV luminosity of 2.2$\times10^{32}$ erg s$^{-1}$-- a superflare, by comparison with energies of typical stellar flares on active binary systems. The trigger spectrum indicates a hot thermal plasma with T$\sim$180 $\times10^{6}$K. X-ray spectral analysis from 0.8--200 keV with the X-Ray Telescope and BAT in the next two orbits reveals evidence for a thermal component (T$>$80 $\times10^{6}$K) and Fe K 6.4 keV emission. A tail of emission out to 200 keV can be fit with either an extremely high temperature thermal plasma (T$\sim3\times10^{8}$K) or power-law emission. Based on analogies with solar flares, we attribute the excess continuum emission to nonthermal thick-target bremsstrahlung emission from a population of accelerated electrons. We estimate the radiated energy from 0.01--200 keV to be $\sim6\times10^{36}$ erg, the total radiated energy over all wavelengths $\sim10^{38}$ erg, the energy in nonthermal electrons above 20 keV $\sim3\times10^{40}$ erg, and conducted energy $<5\times10^{43}$ erg. The nonthermal interpretation gives a reasonable value for the total energy in electrons $>$ 20 keV when compared to the upper and lower bounds on the thermal energy content of the flare. This marks the first occasion in which evidence exists for nonthermal hard X-ray emission from a stellar flare. We investigate the emission mechanism responsible for producing the 6.4 keV feature, and find that collisional ionization from nonthermal electrons appears to be more plausible than the photoionization mechanism usually invoked on the Sun and pre-main sequence stars.Comment: 41 pages, 7 figures, accepted for publication in the Astrophysical Journa

Outlier SNPs enable food traceability of the southern rock lobster, Jasus edwardsii

Recent advances in next-generation sequencing have enhanced the resolution of population genetic studies of non-model organisms through increased marker generation and sample throughput. Using double digest restriction site-associated DNA sequencing (ddRADseq), we investigated the population structure of the commercially important southern rock lobster, Jasus edwardsii, in Australia and New Zealand with the aim of identifying a panel of SNP markers that could be used to trace country of origin. Four ddRADseq libraries comprising a total of 88 individuals were sequenced on the Illumina MiSeq platform, and demultiplexed reads were used to create a reference catalog of loci. Individual reads were then mapped to the reference catalog, and variant calling was performed. We have characterized two single-nucleotide polymorphism (SNP) panels comprised in total of 656 SNPs. The first panel contained 535 neutral SNPs and the second, 121 outlier SNPs that were characteristic of being putatively under selection. Both neutral and outlier SNP panels showed significant differentiation between the two countries, with the outlier loci demonstrating much larger F(ST) values (F(ST) outlier SNP panel = 0.134, P < 0.0001; F(ST) neutral SNP panel = 0.022, P < 0.0001). Assignment tests performed with the outlier SNP panel allocated 100 % of the individuals to country of origin, demonstrating the usefulness of these markers for food traceability of J. edwardsii