Variation in resistance to multiple pathogen species:anther-smuts of Silene uniflora

The occurrence of multiple pathogen species on a shared host species is unexpected when they exploit the same micro-niche within the host individual. One explanation for such observations is the presence of pathogen-specific resistances segregating within the host population into sites that are differentially occupied by the competing pathogens. This study used experimental inoculations to test whether specific resistances may contribute to the maintenance of two species of anther-smut fungi, Microbotryum silenes-inflatae and Microbotryum lagerheimii, in natural populations of Silene uniflora in England and Wales. Overall, resistance to the two pathogens was strongly positively correlated among host populations and to a lesser degree among host families within populations. A few instances of specific resistance were also observed and confirmed by replicated inoculations. The results suggest that selection for resistance to one pathogen may protect the host from the emergence via host shifts of related pathogen species, and conversely that co-occurrence of two species of pathogens may be dependent on the presence of host genotypes susceptible to both

Understanding the role of eco-evolutionary feedbacks in host-parasite coevolution

It is widely recognised that eco-evolutionary feedbacks can have important implications for evolution. However, many models of host-parasite coevolution omit eco-evolutionary feedbacks for the sake of simplicity, typically by assuming the population sizes of both species are constant. It is often difficult to determine whether the results of these models are qualitatively robust if eco-evolutionary feedbacks are included. Here, by allowing interspecific encounter probabilities to depend on population densities without otherwise varying the structure of the models, we provide a simple method that can test whether eco-evolutionary feedbacks per se affect evolutionary outcomes. Applying this approach to explicit genetic and quantitative trait models from the literature, our framework shows that qualitative changes to the outcome can be directly attributable to eco-evolutionary feedbacks. For example, shifting the dynamics between stable monomorphism or polymorphism and cycling, as well as changing the nature of the cycles. Our approach, which can be readily applied to many different models of host-parasite coevolution, offers a straightforward method for testing whether eco-evolutionary feedbacks qualitatively change coevolutionary outcomes

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Social Class

Discussion of class structure in fifth-century Athens, historical constitution of theater audiences, and the changes in the comic representation of class antagonism from Aristophanes to Menander

Ecological and genetic models of host-pathogen coevolution

A model is presented to analyse the forces that maintain genetic polymorphism in interactions between host plants and their pathogens. Genetic variability in hosts occurs for specific resistance to different pathogen races and variability in pathogens occurs for specific virulence to different host races. The model tracks both fluctuating population sizes and changing gene frequencies. Analyses over a range of parameters show that ecological and demographic factors, such as birth and death rates, often have a more profound effect on the amount of polymorphism than genetic parameters, such as the pleiotropic costs of resistance and virulence associated with different alleles. A series of simple measures are proposed to predict the amount of genetic polymorphism expected in particular host-pathogen interactions. These measures can be used to develop and test a comparative theory of genetic polymorphism in host-pathogen coevolution

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A Multi-Step Process of Viral Adaptation to a Mutagenic Nucleoside Analogue by Modulation of Transition Types Leads to Extinction-Escape

Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV) in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S) in the viral polymerase (3D). The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin —by avoiding the biased repertoire of transition mutations produced by this purine analogue—and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP), as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure

Invasion fitness, inclusive fitness, and reproductive numbers in heterogeneous populations.

How should fitness be measured to determine which phenotype or "strategy" is uninvadable when evolution occurs in a group-structured population subject to local demographic and environmental heterogeneity? Several fitness measures, such as basic reproductive number, lifetime dispersal success of a local lineage, or inclusive fitness have been proposed to address this question, but the relationships between them and their generality remains unclear. Here, we ascertain uninvadability (all mutant strategies always go extinct) in terms of the asymptotic per capita number of mutant copies produced by a mutant lineage arising as a single copy in a resident population ("invasion fitness"). We show that from invasion fitness uninvadability is equivalently characterized by at least three conceptually distinct fitness measures: (i) lineage fitness, giving the average individual fitness of a randomly sampled mutant lineage member; (ii) inclusive fitness, giving a reproductive value weighted average of the direct fitness costs and relatedness weighted indirect fitness benefits accruing to a randomly sampled mutant lineage member; and (iii) basic reproductive number (and variations thereof) giving lifetime success of a lineage in a single group, and which is an invasion fitness proxy. Our analysis connects approaches that have been deemed different, generalizes the exact version of inclusive fitness to class-structured populations, and provides a biological interpretation of natural selection on a mutant allele under arbitrary strength of selection