Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after six years of macrocyclic lactone use

Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class, the macrocyclic lactones, are not known and sensitive diagnostic tools based on molecular markers are not currently available. This prohibits accurate surveillance of resistance or assessment of strategies aimed at controlling its spread. In this study, we examined four UK field populations of Haemonchus contortus, differing in macrocyclic lactone treatment history, for evidence of selection at ‘candidate gene’ loci identified as determining macrocyclic lactone resistance in previously published research. Individual worms were genotyped at Hc-lgc-37, Hc-glc-5, Hc-avr-14 and Hc-dyf-7, and four microsatellite loci. High levels of polymorphism were identified at the first three candidate gene loci with remarkably little polymorphism at Hc-dyf-7. While some between-population comparisons of individual farms with and without long-term macrocyclic lactone use identified statistically significant differences in allele frequency and/or fixation index at the Hc-lgc-37, Hc-glc-5 or Hc-avr-14 loci, we found no consistent evidence of selection in other equivalent comparisons. While it is possible that different mechanisms are important in different populations or that resistance may be conferred by small changes at multiple loci, our findings suggest that these are unlikely to be major loci conferring macrocyclic lactone resistance on UK farms or suitable for diagnostic marker development. More powerful approaches, using genome-wide or whole genome sequencing, may be required to define macrocyclic lactone resistance loci in such genetically variable populations

Six types of E−E-functions of the Lie groups O(5) and G(2)

New families of $E$-functions are described in the context of the compact simple Lie groups O(5) and G(2). These functions of two real variables generalize the common exponential functions and for each group, only one family is currently found in the literature. All the families are fully characterized, their most important properties are described, namely their continuous and discrete orthogonalities and decompositions of their products.Comment: 25 pages, 13 figure

Baroclinic adjustment and dissipative control of storm tracks

The steady-state response of a mid-latitude storm track to large-scale extratropical thermal forcing and eddy friction is investigated in a dry general circulation model with a zonally symmetric forcing. A two-way equilibration is found between the relative responses of the mean baroclinicity and baroclinic eddy intensity, whereby mean baroclinicity responds more strongly to eddy friction whereas eddy intensity responds more strongly to the thermal forcing of baroclinicity. These seemingly counter-intuitive responses are reconciled using the steady state of a predator-prey relationship between baroclinicity and eddy intensity. This relationship provides additional support for the well studied mechanism of baroclinic adjustment in the Earth’s atmosphere, as well as providing a new mechanism whereby eddy dissipation controls the large-scale thermal structure of a baroclinically unstable atmosphere. It is argued that these two mechanisms of baroclinic adjustment and dissipative control should be used in tandem when considering storm track equilibration

Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA

SMC5/6 is a highly conserved protein complex related to cohesin and condensin, which are the key components of higher-order chromatin structures. The SMC5/6 complex is essential for proliferation in yeast and is involved in replication fork stability and processing. However, the precise mechanism of action of SMC5/6 is not known. Here we present evidence that the NSE1/NSE3/NSE4 sub-complex of SMC5/6 binds to double-stranded DNA without any preference for DNA-replication/recombination intermediates. Mutations of key basic residues within the NSE1/NSE3/NSE4 DNA-binding surface reduce binding to DNA in vitro. Their introduction into the Schizosaccharomyces pombe genome results in cell death or hypersensitivity to DNA damaging agents. Chromatin immunoprecipitation analysis of the hypomorphic nse3 DNA-binding mutant shows a reduced association of fission yeast SMC5/6 with chromatin. Based on our results, we propose a model for loading of the SMC5/6 complex onto the chromatin

Exhaustive enumeration unveils clustering and freezing in random 3-SAT

We study geometrical properties of the complete set of solutions of the random 3-satisfiability problem. We show that even for moderate system sizes the number of clusters corresponds surprisingly well with the theoretic asymptotic prediction. We locate the freezing transition in the space of solutions which has been conjectured to be relevant in explaining the onset of computational hardness in random constraint satisfaction problems.Comment: 4 pages, 3 figure

Vertical transmission of hepatitis C virus: systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review of estimates of hepatitis C virus (HCV) vertical transmission risk to update current estimates published more than a decade ago. METHODS: PubMed and Embase were searched and 109 articles were included. Pooled estimates of risk were generated for children born to HCV antibody-positive and viremic women, aged ≥18 months, separately by maternal human immunodeficiency virus (HIV) coinfection. RESULTS: Meta-analysis of the risk of vertical HCV infection to children of HCV antibody-positive and RNA-positive women was 5.8% (95% confidence interval [CI], 4.2%-7.8%) for children of HIV-negative women and 10.8% (95% CI, 7.6%-15.2%) for children of HIV-positive women. The adjusted meta-regression model explained 51% of the between-study variation in the 25 included risk estimates. Maternal HIV coinfection was the most important determinant of vertical transmission risk (adjusted odds ratio, 2.56 [95% CI, 1.50-4.43]). Additional methodological (follow-up rate and definition of infection in children) and risk factors independently predicted HCV infection and need to be captured and reported by future studies of vertical transmission. Studies assessing the contribution of nonvertical exposures in early childhood to HCV prevalence among children at risk of vertical transmission are needed. CONCLUSIONS: More than 1 in every 20 children delivered by HCV chronically infected women are infected, highlighting that vertical transmission likely constitutes the primary transmission route among children. These updated estimates are a basis for decision making in prioritization of research into risk-reducing measures, and inform case management in clinical settings, especially for HIV-positive women in reproductive age

The Origins, Meaning and Use of Nicknames in Czech Villages in Bulgaria

Příspěvek se zabývá problematikou jmen a strategiemi pojmenovávání u bulharských Čechů, evangelíků, kteří žili v první polovině 20. století ve dvou bulharských obcích, Vojvodovo a Belinci. Vychází přitom z dat získaných během terénních šetření v několika obcích na Valticku a Mikulovsku, kde dnes žijí přesídlenci z Bulharska a jejich potomci. V textu jsou vedle rodných jmen a příjmení analyzovány zejména přezdívky bulharských Čechů vzhledem k jejich původu, významu a způsobu užívání. Přezdívky, které se zde vyvinuly jako třetí klasifikační systém (vedle rodných jmen a příjmení), jsou klasifikovány do několika kategorií a je sledován jejich význam pro dané společenství. Text se zabývá také strategiemi dávání, užívání či zamlčování přezdívek v různých kontextech, a sleduje danou problematiku ve vztahu k systému pojmenovávání v rámci sociálního prostředí, které dané společenství obklopovalo (bulharské pravoslavné obyvatelstvo). Poukazuje pak také na skutečnost, že v rámci Vojvodova byly používány dva odlišné soubory přezdívek pro stejné osoby, což odráží existenci dvou různých morálních společenství v rámci jedné obce.The article deals with naming practices among Czechs who lived in the first half of 20th century in two Bulgarian villages – Vojvodovo and Belinci, and who left Bulgaria after WWII. The text analyzes the origins, the use and the meaning of nicknames in the studied population in 1900–1950. It draws on fieldwork carried out among the people who migrated from Bulgaria and settled in several towns and villages in South Moravia (region of Mikulov and Valtice) and their descendants. Naming practices of Bulgarian Czechs are analyzed in relation to naming strategies of Bulgarians. Nicknames are classified into several groups: patronymic nicknames, occupational nicknames and unique personal nicknames. The system of nicknames, which evolved as a third classificatory element to help organize the local social world, is studied in respect to strategies of giving, using and concealing nicknames in different contexts. Two sets of nicknames, used by the Czech and Bulgarian inhabitants of the village, respectively, are studied as an expression of the existence of two distinctive moral communities

The Phase Diagram of 1-in-3 Satisfiability Problem

We study the typical case properties of the 1-in-3 satisfiability problem, the boolean satisfaction problem where a clause is satisfied by exactly one literal, in an enlarged random ensemble parametrized by average connectivity and probability of negation of a variable in a clause. Random 1-in-3 Satisfiability and Exact 3-Cover are special cases of this ensemble. We interpolate between these cases from a region where satisfiability can be typically decided for all connectivities in polynomial time to a region where deciding satisfiability is hard, in some interval of connectivities. We derive several rigorous results in the first region, and develop the one-step--replica-symmetry-breaking cavity analysis in the second one. We discuss the prediction for the transition between the almost surely satisfiable and the almost surely unsatisfiable phase, and other structural properties of the phase diagram, in light of cavity method results.Comment: 30 pages, 12 figure

Comparative marine biodiversity and depth zonation in the Southern Ocean: evidence from a new large polychaete dataset from Scotia and Amundsen seas

Based on a dataset of 16,991 and 307 morphospecies of polychaete worms collected from 58 epibenthic sledge deployments across the Scotia and Amundsen Seas, we show that the structures of their shelf, deep-shelf and slope communities are composed of distinct polychaete assemblages spanning regions with “high”, “intermediate”, and “low” biodiversity. Depth has been identified as the main factor structuring the polychaete communities in both seas, countering the prevalent notion of extended eurybathy of the Southern Ocean benthos. From an evolutionary perspective, this strong dissimilarity between shelf and slope fauna could be interpreted as evidence for survival in shelf refugias, rather than migration into deeper waters during glacial maxima. The previously unsampled Amundsen Sea is shown to be diverse, harbouring a high level of taxonomic novelty, with many species new to science. The polychaete community of the inner shelf in the Amundsen Sea (Pine Island Bay) has also been shown to be of deep-sea character, likely due to intrusion of the Circumpolar Deep Water onto the shelf. In the Scotia Sea, our data support the notion of relatively high biodiversity of waters around the South Orkney Islands, South Georgia, and Shag Rocks (all recently established as Marine Protected Areas) and depressed diversity in the extreme environment of Southern Thule