34 research outputs found

    Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes

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    Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections. Understanding the evolutionary dynamics of HCMV is essential for the development of effective new drugs and vaccines. By comparing viral genomes from uncultivated or low-passaged clinical samples of diverse origins, we observe evidence of frequent homologous recombination events, both recent and ancient, and no structure of HCMV genetic diversity at the whole-genome scale. Analysis of individual gene-scale loci reveals a striking dichotomy: while most of the genome is highly conserved, recombines essentially freely and has evolved under purifying selection, 21 genes display extreme diversity, structured into distinct genotypes that do not recombine with each other. Most of these hyper-variable genes encode glycoproteins involved in cell entry or escape of host immunity. Evidence that half of them have diverged through episodes of intense positive selection suggests that rapid evolution of hyper-variable loci is likely driven by interactions with host immunity. It appears that this process is enabled by recombination unlinking hyper-variable loci from strongly constrained neighboring sites. It is conceivable that viral mechanisms facilitating super-infection have evolved to promote recombination between diverged genotypes, allowing the virus to continuously diversify at key loci to escape immune detection, while maintaining a genome optimally adapted to its asymptomatic infectious lifecycle

    Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

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    7191/Mar294

    FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

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    FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity

    Mate availability and fecundity selection in multi-allelic self-incompatibility systems in plants

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    We investigate mate availability in different models of multiallelic self-incompatibility systems in mutation-selection-drift balance in finite populations. Substantial differences among self-incompatibility systems occur in average mate availability, and in variances of mate availability among individual plants. These differences are most pronounced in small populations in which low mate availability may reduce seed set in some types of sporophytic self-incompatibility. In cases where the pollination system causes a restriction in the number of pollen genotypes available to an individual plant, the fecundity of that plant depends on the availability of compatible pollen, which is determined by its genotype at the incompatibility locus. This leads to an additional component of selection acting on self-incompatibility systems, which we term 'fecundity selection.' Fecundity selection increases the number of alleles maintained in finite populations and increases mate availability in small populations. The strength of fecundity selection is dependent on the type of self-incompatibility. In some cases, fecundity selection markedly alters the equilibrium dynamics of self-incompatibility alleles. We discuss the population genetic consequences of mate availability and fecundity selection in the contexts of conservation management of self-incompatible plant species and experimental investigations on self-incompatibility in natural populations.SCOPUS: re.jFLWINinfo:eu-repo/semantics/publishe

    Effect of low temperature carburization of austenitic stainless steels on residual stress and magnetic properties

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    Low temperature carburizing of a series of austenitic stainless with various combinations of chromium and nickel equivalents was performed. The investigation of the response towards low temperature carburized for three stainless steels with various Cr- and Ni-equivalents showed that the carbon uptake depends significantly on the chemical composition of the base material. The higher carbon content in the expanded austenite layer of specimen 6 (1.4565) and specimen 4 (1.4539/AISI 904L) compared to specimen 2 (1.4404/AISI 316L) is assumed to be mainly related to the difference in the specimens’ chromium content. More chromium leads to more lattice expansion. Along with the higher carbon content, higher hardness values and higher compressive residual stresses in the expanded austenite zone are introduced than for low temperature carburized AISI 316L. The residual stresses obtained from X-ray diffraction lattice strain investigation depend strongly on the chosen X-ray elastic constants. Presently, no values are known for carbon (or nitrogen) stabilized expanded austenite. Nevertheless, first principle elastic constants for γ′&minus Fe4C appear to provide realistic residual stress values. Magnetic force microscopy and measurement with an eddy current probe indicate that austenitic stainless steels can become ferromagnetic upon carburizing, similar for low temperature nitriding. The apparent transition from para- to ferromagnetism cannot be attributed entirely to the interstitially dissolved carbon content in the formed expanded austenite layer but appears to depend also on the metallic composition of the alloy, in particular the Ni content
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