The Structure of Allelic Diversity in the Presence of Purifying Selection

In the absence of selection, the structure of equilibrium allelic diversity is described by the elegant sampling formula of Ewens. This formula has helped shape our expectations of empirical patterns of molecular variation. Along with coalescent theory, it provides statistical techniques for rejecting the null model of neutrality. However, we still do not fully understand the statistics of the allelic diversity expected in the presence of natural selection. Earlier work has described the effects of strongly deleterious mutations linked to many neutral sites, and allelic variation in models where offspring fitness is unrelated to parental fitness, but it has proven difficult to understand allelic diversity in the presence of purifying selection at many linked sites. Here, we study the population genetics of infinitely many perfectly linked sites, some neutral and some deleterious. Our approach is based on studying the lineage structure within each class of individuals of similar fitness in the deleterious mutation-selection balance. Consistent with previous observations, we find that for moderate and weak selection pressures, the patterns of allelic diversity cannot be described by a neutral model for any choice of the effective population site. We compute precisely how purifying selection at many linked sites distorts the patterns of allelic diversity, by developing expressions for the likelihood of any configuration of allelic types in a sample analogous to the Ewens sampling formula.Organismic and Evolutionary Biolog

The Structure of Genealogies in the Presence of Purifying Selection: a "Fitness-Class Coalescent"

Compared to a neutral model, purifying selection distorts the structure of genealogies and hence alters the patterns of sampled genetic variation. Although these distortions may be common in nature, our understanding of how we expect purifying selection to affect patterns of molecular variation remains incomplete. Genealogical approaches such as coalescent theory have proven difficult to generalize to situations involving selection at many linked sites, unless selection pressures are extremely strong. Here, we introduce an effective coalescent theory (a "fitness-class coalescent") to describe the structure of genealogies in the presence of purifying selection at many linked sites. We use this effective theory to calculate several simple statistics describing the expected patterns of variation in sequence data, both at the sites under selection and at linked neutral sites. Our analysis combines a description of the allele frequency spectrum in the presence of purifying selection with the structured coalescent approach of Kaplan et al. (1988), to trace the ancestry of individuals through the distribution of fitnesses within the population. We also derive our results using a more direct extension of the structured coalescent approach of Hudson and Kaplan (1994). We find that purifying selection leads to patterns of genetic variation that are related but not identical to a neutrally evolving population in which population size has varied in a specific way in the past.Organismic and Evolutionary Biolog

Abundance of actinobacteria and production of geosmin and 2-methylisoborneol in Danish streams and fish ponds

Occurrence of the odours geosmin and 2-methylisoborneol (MIB) in freshwater environments indicates that odour-producing organisms are commonly occurring. In the present study, we assumed actinomycetes to be a major source of the odours. Seasonal concentrations of odours and abundance of Actinobacteria, which includes actinomycetes and other G+ and high GC bacteria, were determined in one oligotrophic and two eutrophic freshwater streams, as well as in aquacultures connected to these streams, in Denmark. Concentrations of geosmin and MIB ranged from 2 to 9 ng l−1 and were lowest in the winter. Passage of stream water in the aquacultures increased the amount of geosmin and MIB by up to 55% and 110%, respectively. Densities of actinobacteria were determined by fluorescence in situ hybridization with catalyzed reporter deposition (CARD-FISH) technique and were found to make up from 4 to 38 × 107 cells l−1, corresponding to 3–9% of the total bacterial populations. The lowest densities of actinobacteria occurred in the winter. Filamentous bacteria targeted by the FISH probe made up about 2.7–38% (average was 22%) of the actinobacteria and were expected to be actinomycetes. Combined microautoradiography and CARD-FISH demonstrated that 10–38% (incorporation of 3H-thymidine) and 41–65% (incorporation of 3H-leucine) of the actinobacteria were metabolically active. The proportion of active actinobacteria increased up to 2-fold during passage of stream water in the aquacultures, and up to 98% of the cells became active. Sequencing of 16S rRNA genes in 8 bacterial isolates with typical actinomycete morphology from the streams and ponds demonstrated that most of them belonged to the genus Streptomyces. The isolated actinomycetes produced geosmin at rates from 0.1 to 35 ag geosmin bacterium−1 h−1. MIB was produced at similar rates in 5 isolates, whereas no MIB was produced by three of the isolates. Addition of the odours to stream water demonstrated that indigenous stream bacteria were capable of reducing the odours, and that enrichment with LB medium stimulated the degradation. Our study shows that bacterial communities in freshwater include geosmin- and MIB-producing actinobacteria. However, the mechanisms controlling production as well as degradation of the odours in natural waters appear complex and require further research

Hospital Records of Pain, Fatigue, or Circulatory Symptoms in Girls Exposed to Human Papillomavirus Vaccination: Cohort, Self-Controlled Case Series, and Population Time Trend Studies

Human papillomavirus (HPV) vaccination has been associated with subsequent diffuse symptoms in girls, reducing public confidence in the vaccine. We examined whether girls have nonspecific outcomes of HPV vaccination, using triangulation from cohort, self-controlled case series (SCCS), and population time trend analyses carried out in Denmark between 2000 and 2014. The study population consisted of 314,017 HPV-vaccinated girls and 314,017 age-matched HPV-unvaccinated girls (cohort analyses); 11,817 girls with hospital records (SCCS analyses); and 1,465,049 girls and boys (population time trend analyses). The main outcome measures were hospital records of pain, fatigue, or circulatory symptoms. The cohort study revealed no increased risk among HPV vaccine-exposed girls, with incidence rate ratios close to 1.0 for abdominal pain, nonspecific pain, headache, hypotension/syncope, tachycardia (including postural orthostatic tachycardia syndrome), and malaise/fatigue (including chronic fatigue syndrome). In the SCCS analyses, we observed no association between HPV vaccination and subsequent symptoms. In time trend analyses, we observed a steady increase in these hospital records in both girls and (HPV-unvaccinated) boys, with no relationship to the 2009 introduction of HPV vaccine to Denmark’s vaccination program. This study, which had nationwide coverage, showed no evidence of a causal link between HPV vaccination and diffuse autonomic symptoms leading to hospital contact

Rotational cooling of molecules using lamps

We investigate theoretically the application of tailored incoherent far-infrared fields in combination with laser excitation of a single rovibrational transition for rotational cooling of translationally cold polar diatomic molecules. The cooling schemes are effective on a timescale shorter than typical unperturbed trapping times in ion traps and comparable to obtainable confinement times of neutral molecules.Comment: 5 pages, 2 figure

An evaluation of Bradfordizing effects

The purpose of this paper is to apply and evaluate the bibliometric method Bradfordizing for information retrieval (IR) experiments. Bradfordizing is used for generating core document sets for subject-specific questions and to reorder result sets from distributed searches. The method will be applied and tested in a controlled scenario of scientific literature databases from social and political sciences, economics, psychology and medical science (SOLIS, SoLit, USB Köln Opac, CSA Sociological Abstracts, World Affairs Online, Psyndex and Medline) and 164 standardized topics. An evaluation of the method and its effects is carried out in two laboratory-based information retrieval experiments (CLEF and KoMoHe) using a controlled document corpus and human relevance assessments. The results show that Bradfordizing is a very robust method for re-ranking the main document types (journal articles and monographs) in today’s digital libraries (DL). The IR tests show that relevance distributions after re-ranking improve at a significant level if articles in the core are compared with articles in the succeeding zones. The items in the core are significantly more often assessed as relevant, than items in zone 2 (z2) or zone 3 (z3). The improvements between the zones are statistically significant based on the Wilcoxon signed-rank test and the paired T-Test