Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

Pathways to social inequality

Social inequality is now pervasive in human societies, despite the fact that humans lived in relatively egalitarian, small-scale societies across most of our history. Prior literature highlights the importance of environmental conditions, economic defensibility, and wealth transmission for shaping early Holocene origins of social inequality. However, it remains untested whether the mechanisms that drive the evolution of inequality in recent human societies follow a similar trajectory. We conduct the first global analysis of pathways to inequality within modern human societies using structural equation modeling. Our analytical approach demonstrates that environmental conditions, resource intensification, and wealth transmission mechanisms impact various forms of social inequality via a complex web of causality. We further find that subsistence practices have a direct impact on some institutionalized forms of inequality. This work identifies drivers of social inequality in the modern world and demonstrates the application of structural equation modeling methods to investigate complex relationships between elements of human culture

Pathways to social inequality

Social inequality is now pervasive in human societies, despite the fact that humans lived in relatively egalitarian, small-scale societies across most of our history. Prior literature highlights the importance of environmental conditions, economic defensibility, and wealth transmission for shaping early Holocene origins of social inequality. However, it remains untested whether the mechanisms that drive the evolution of inequality in recent human societies follow a similar trajectory. We conduct the first global analysis of pathways to inequality within modern human societies using structural equation modeling. Our analytical approach demonstrates that environmental conditions, resource intensification, and wealth transmission mechanisms impact various forms of social inequality via a complex web of causality. We further find that subsistence practices have a direct impact on some institutionalized forms of inequality. This work identifies drivers of social inequality in the modern world and demonstrates the application of structural equation modeling methods to investigate complex relationships between elements of human culture

Ecological and cultural factors underlying the global distribution of prejudice

Prejudiced attitudes and political nationalism vary widely around the world, but there has been little research on what predicts this variation. Here we examine the ecological and cultural factors underlying the worldwide distribution of prejudice. We suggest that cultures grow more prejudiced when they tighten cultural norms in response to destabilizing ecological threats. A set of seven archival analyses, surveys, and experiments (∑N = 3,986,402) find that nations, American states, and pre-industrial societies with tighter cultural norms show the most prejudice based on skin color, religion, nationality, and sexuality, and that tightness predicts why prejudice is often highest in areas of the world with histories of ecological threat. People’s support for cultural tightness also mediates the link between perceived ecological threat and intentions to vote for nationalist politicians. Results replicate when controlling for economic development, inequality, conservatism, residential mobility, and shared cultural heritage. These findings offer a cultural evolutionary perspective on prejudice, with implications for immigration, intercultural conflict, and radicalization.publishedVersio

The global geography of human subsistence

How humans obtain food has dramatically reshaped ecosystems and altered both the trajectory of human history and the characteristics of human societies. Our species' subsistence varies widely, from predominantly foraging strategies, to plant-based agriculture and animal husbandry. The extent to which environmental, social and historical factors have driven such variation is currently unclear. Prior attempts to resolve long-standing debates on this topic have been hampered by an over-reliance on narrative arguments, small and geographically narrow samples, and by contradictory findings. Here we overcome these methodological limitations by applying multi-model inference tools developed in biogeography to a global dataset (818 societies). Although some have argued that unique conditions and events determine each society's particular subsistence strategy, we find strong support for a general global pattern in which a limited set of environmental, social and historical factors predicts an essential characteristic of all human groups: how we obtain our food

Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

A significant challenge in chemistry is to rationally reproduce the functional potency of a protein in a small molecule, which is cheaper to manufacture, non-immunogenic, and also both stable and bioavailable. Synthetic peptides corresponding to small bioactive protein surfaces do not form stable structures in water and do not exhibit the functional potencies of proteins. Here we describe a novel approach to growing small molecules with protein-like potencies from a functionally important amino acid of a protein. A 77-residue human inflammatory protein (complement C3a) important in innate immunity is rationally transformed to equipotent small molecules, using peptide surrogates that incorporate a turn-inducing heterocycle with correctly positioned hydrogen-bond-accepting atoms. Small molecule agonists (molecular weigh

The Global Jukebox: A public database of performing arts and culture

Standardized cross-cultural databases of the arts are critical to a balanced scientific under- standing of the performing arts, and their role in other domains of human society. This paper introduces the Global Jukebox as a resource for comparative and cross-cultural study of the performing arts and culture. The Global Jukebox adds an extensive and detailed global database of the performing arts that enlarges our understanding of human cultural diversity. Initially prototyped by Alan Lomax in the 1980s, its core is the Cantometric s dataset, encompassing standardized codings on 37 aspects of musical style for 5,776 traditional songs from 1,026 societies. The Cantometrics dataset has been cleaned and checked for reliability and accuracy, and includes a full coding guide with audio training examples ( https:// theglobaljukebox. org/?songsofearth ). Also being released are seven additional datasets coding and describing instrumentation, conversation, popular music, vowel and consonant placement, breath management , social factors, and societies. For the first time, all digitized Global Jukebox data are being made available in open-access, downloadable format ( https://github.com/theglobaljukebox ), linked with streaming audio recordings (theglobaljukebox.org) to the maximum extent allowed while respecting copyright and the wishes of cul- ture-bearers. The data are cross-indexed with the Database of Peoples, Languages, and Cultures (D-PLACE) to allow researchers to test hypotheses about worldwide coevolution of aesthetic patterns and traditions. As an example, we analyze the global relationship between song style and societal complexity, showing that they are robustly related, in contrast to previous critiques claiming that these proposed relationships were an artifact of autocorrelation (though causal mechanisms remain unresolved