Within-epitope interactions affect CTL-escape estimation

As human immunodeficiency virus (HIV) begins to replicate within hosts, immune responses are elicited against it. Escape mutations in viral epitopes-immunogenic peptide parts presented on the surface of infected cells-allow HIV to partially evade these responses, and thus rapidly go to fixation. The faster they go to fixation, i.e., the higher their escape rate, the larger the selective pressure exerted by the immune system is assumed to be. This relation underpins the rationale for using escapes to assess the strength of immune responses. However, escape rate estimates are often obtained by employing an aggregation procedure, where several mutations that affect the same epitope are aggregated into a single, composite epitope mutation. The aggregation procedure thus rests upon the assumption that all within-epitope mutations have indistinguishable effects on immune recognition. In this study, we investigate how violation of this assumption affects escape rate estimates. To this end, we extend a previously developed simulation model of HIV that accounts for mutation, selection, and recombination to include different distributions of fitness effects (DFEs) and inter-mutational genomic distances. We use this discrete time Wright-Fisher based model to simulate early within-host evolution of HIV for DFEs and apply standard estimation methods to infer the escape rates. We then compare true with estimated escape rate values. We also compare escape rate values obtained by applying the aggregation procedure with values estimated without use of that procedure. We find that across the DFEs analyzed, the aggregation procedure alters the detectability of escape mutations: large-effect mutations are overrepresented while small-effect mutations are concealed. The effect of the aggregation procedure is similar to extracting the largest-effect mutation appearing within an epitope. Furthermore, the more pronounced the over-exponential decay of the DFEs, the more severely true escape rates are underestimated. We conclude that the aggregation procedure has two main consequences. On the one hand, it leads to a misrepresentation of the DFE of fixed mutations. On the other hand, it conceals within-epitope interactions that may generate irregularities in mutation frequency trajectories that are thus left unexplained

Bayesian estimation of range for microsatellite loci.

Microsatellite loci have become important in population genetics because of their high level of polymorphism in natural populations, very frequent occurrence throughout the genome, and apparently high mutation rate. Observed repeat numbers (alleles size) in natural populations and expectations based on computer simulations suggest that the range of repeat numbers at a microsatellite locus is restricted. This range is a key parameter that should be properly estimated in order to proceed with calculations of divergence times in phylogenetic studies and to better investigate the within- and between-population variability. The 'plug-in' estimate of range based on the minimum and maximum value observed in a sample is not satisfactory because of the relatively large number of alleles in comparison with typical sample sizes. In this paper, a set of data from 30 dinucleotide microsatellite loci is analysed under the assumption of independence among loci. Bayesian inference on range for one locus is obtained by assuming that constraints on range values exist as sharp bounds. Closed-form calculations and robustness revealed by our analysis suggest that the proposed Bayesian approach might be routinely used by researchers to classify microsatellite loci according to the estimated value of their allelic range

Marriage Squeeze, Never-Married Proportion, and Mean Age at First Marriage in China

China’s sex ratio imbalance and the surplus of males have received a great deal of attention, but measures of the extent of the marriage squeeze do not take into account the marital status of population. In this paper, we devise an index of the marriage squeeze for the never-married population and use it to project the male marriage squeeze from 2000 to 2060. From the predicted population and nuptiality tables, we estimate trends in the proportion of men that never marry by age 50 and the mean age at first marriage. We find that the marriage squeeze is much more intense if only the never-married population is considered, rather than including all people without distinguishing their marital status. As the lifelong never-married proportion increases, mean age at first marriage rises first and then declines

Substantive Progress or Neoliberalism in Disguise? An Analysis of the World Bank’s Discourse on Corruption since 1995

I undertake a discourse analysis of World Bank documents from 1995 to the present to explore scholarly debates surrounding the question, “To what extent are the World Bank’s efforts to combat corruption evidence of its attempts to further the neoliberal agenda, characterized by the original Washington Consensus?” Since the late 1990’s, the World Bank has been a leader in the fight against corruption, integrating anti-corruption into its operations worldwide and making it a major issue addressed in World Development Reports, Presidential speeches, and specific anti-corruption strategies. While some scholars see this as an evolutionary move away from neoliberalism, others see the focus on corruption as a way for the Bank to continue to advance and expand the neoliberal agenda after the failure of structural adjustment programs. I argue that while the World Bank’s anti-corruption strategy featured distinctly neoliberal ideals in its early years, over time it has moved away from a focus on liberalization and competition to a more holistic focus on transparency and civic participation as pillars of good governance

Investigating the consequences of interference between multiple CD8+ T cell escape mutations in early HIV infection

During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV's genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains – an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction – could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by interference effects cannot simply be overcome by improved sampling frequencies or sizes. This problem is a consequence of the fundamental shortcomings of current estimation techniques under interference regimes. Hence, accounting for the stochastic nature of competition between mutations demands novel estimation methodologies based on the analysis of HIV strains, rather than mutation frequencies

Cultural transmission of move choice in chess

The study of cultural evolution benefits from detailed analysis of cultural transmission in specific human domains. Chess provides a platform for understanding the transmission of knowledge due to its active community of players, precise behaviors, and long-term records of high-quality data. In this paper, we perform an analysis of chess in the context of cultural evolution, describing multiple cultural factors that affect move choice. We then build a population-level statistical model of move choice in chess, based on the Dirichlet-multinomial likelihood, to analyze cultural transmission over decades of recorded games played by leading players. For moves made in specific positions, we evaluate the relative effects of frequency-dependent bias, success bias, and prestige bias on the dynamics of move frequencies. We observe that negative frequency-dependent bias plays a role in the dynamics of certain moves, and that other moves are compatible with transmission under prestige bias or success bias. These apparent biases may reflect recent changes, namely the introduction of computer chess engines and online tournament broadcasts. Our analysis of chess provides insights into broader questions concerning evolution of human behavioral preferences and modes of social learning.Comment: 25 page

HOUSEHOLDS' RISK MANAGEMENT STRAGIES AND VULNERABILITY TO POVERTY IN RURAL CHINA

N° ISBN - 978-2-7380-1284-5International audienceThis article concerns the effectiveness of risk management strategies adopted by Chinese rural households, in western China where the economic and social context has changed greatly since the late 1990s. Drawing on an existing framework of risk management and vulnerability to poverty, we propose a new model based on qualitative data analysis and test it using quantitative data. We find that risk management strategies include selfinsurance instruments, which involve households' assets and income diversification, and a risk-sharing strategy. Income diversification, precautionary financial saving, and informal social supports are major risk management strategies, which can be effective in reducing vulnerability. Compared with results of previous studies, we find risk management strategies have been revised; the revisions are caused by the rapid social and economic changes that have taken place since the late 1990s

Seeing shapes and hearing textures: Two neural categories of touch

Touching for shape recognition has been shown to activate occipital areas in addition to somatosensory areas. In this study we asked if this combination of somatosensory and other sensory processing areas also exist in other kinds of touch recognition. In particular, does touch for texture roughness matching activate other sensory processing areas apart from somatosensory areas? We addressed this question with functional magnetic resonance imaging (fMRI) using wooden abstract stimulus objects whose shape or texture were to be identified. The participants judged if pairs of objects had the same shape or the same texture. We found that the activated brain areas for texture and shape matching have similar underlying structures, a combination of the primary motor area and somatosensory areas. Areas associated with object-shape processing were activated between stimuli during shape matching and not texture roughness matching, while auditory areas were activated during encoding of texture and not for shape stimuli. Matching of textures also involves left BA47, an area associated with retrieval of relational information. We suggest that texture roughness is recognized in a framework of ordering. Left-lateralized activations favoring texture might reflect semantic processing associated with grading roughness quantitatively, as opposed to the more qualitative distinctions between shapes.publishedVersio