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

Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys

Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine). Methadone, morphine, and nalbuphine each produced dose-dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg). SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception

The evolution and ecology of land ownership

Land ownership norms play a central role in social-ecological systems, and have been studied extensively as a component of ethnographies. Yet only recently has the distribution of land ownership norms across cultures been examined from evolutionary and ecological perspectives. Here we incorporate evolutionary and macroecological modelling to test associations between land ownership norms and environmental, subsistence, and cultural contact predictors for societies in the Bantu language family. We find that Bantu land ownership norms likely evolved on a unilinear trajectory, but not necessarily one requiring consistent increase in exclusivity as suggested by prior theory. Our macroecological analyses suggest that Bantu societies are more likely to have some form of ownership when their neighbors also do. We also find an effect of environmental productivity, supporting resource defensibility theory, which posits that land ownership is more likely where productivity is predictable. We find less support for a proposed link between agricultural intensification and land ownership. Overall, we demonstrate the value of combining analytical approaches from evolution and ecology to test diverse hypotheses on land ownership across a range of disciplines.1. Introduction 2. Materials and methods 2.1 Data 2.2 Phylogenetic analyses of evolution of land ownership 2.3 Multi-model inference of drivers of spatial patterns in land ownership 3. Results 3.1 Evolutionary trajectories of land ownership 3.2 Drivers of spatial variation in land ownership 4. Discussio

Identification of Native Defects (Vacancies and Antisites) in CdSiP2 Crystals

Electron paramagnetic resonance (EPR) is used to identify four native defects in single crystals of CdSiP2. This nonlinear optical material is used in optical parametric oscillators to generate tunable output in the mid-infrared. The performance of these frequency-conversion devices is limited when infrared absorption bands associated with native defects overlap a pump wavelength. Cadmium, silicon, and phosphorus vacancies and also silicon-on-cadmium antisites are present in the as-grown undoped CdSiP2 crystals. Using near-band-edge 632.8 nm light from a He-Ne laser, a paramagnetic charge state, and thus an EPR spectrum, is formed at liquid-helium temperatures for three of the four defects. The EPR spectrum from the singly ionized silicon vacancy (V-Si) is present without light and has five hyperfine lines due to equal interactions with the four neighboring 31P nuclei. In contrast, the photoinduced EPR spectrum from the singly ionized cadmium vacancy (V-Cd) has a three-line hyperfine pattern due to equal interactions with only two of its four neighboring 31P nuclei. The light-induced spectrum from the singly ionized silicon-on-cadmium antisite (Si+Cd) also has a three-line hyperfine pattern, thus indicating that the unpaired spin interacts primarily with only two 31P neighbors. For the neutral phosphorus vacancy (V0P), the unpaired spin is primarily localized on the nearest-neighbor silicon ions and the photoinduced EPR spectrum has no resolved 31P hyperfine interactions. The silicon and cadmium vacancies are acceptors, and the silicon-on-cadmium antisite and the phosphorus vacancy are donors

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

Estimating taxon-specific population dynamics in diverse microbial communities

Understanding how population-level dynamics contribute to ecosystem-level processes is a primary focus of ecological research and has led to important breakthroughs in the ecology of macroscopic organisms. However, the inability to measure population-specific rates, such as growth, for microbial taxa within natural assemblages has limited ecologists’ understanding of how microbial populations interact to regulate ecosystem processes. Here, we use isotope incorporation within DNA molecules to model taxon- specific population growth in the presence of 18O-labeled water. By applying this model to phylogenetic marker sequencing data collected from stable-isotope probing studies, we estimate rates of growth, mortal- ity, and turnover for individual microbial populations within soil assemblages. When summed across the entire bacterial community, our taxon-specific estimates are within the range of other whole-assemblage measurements of bacterial turnover. Because it can be applied to environmental samples, the approach we present is broadly applicable to measuring population growth, mortality, and associated biogeochemical process rates of microbial taxa for a wide range of ecosystems and can help reveal how individual microbial populations drive biogeochemical fluxes

DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing

Virus infection is sensed by pattern recognition receptors (PRRs) detecting virus nucleic acids and initiating an innate immune response. DNA-dependent protein kinase (DNA-PK) is a PRR that binds cytosolic DNA and is antagonized by vaccinia virus (VACV) protein C16. Here, VACV protein C4 is also shown to antagonize DNA-PK by binding to Ku and blocking Ku binding to DNA, leading to a reduced production of cytokines and chemokines in vivo and a diminished recruitment of inflammatory cells. C4 and C16 share redundancy in that a double deletion virus has reduced virulence not seen with single deletion viruses following intradermal infection. However, non-redundant functions exist because both single deletion viruses display attenuated virulence compared to wild-type VACV after intranasal infection. It is notable that VACV expresses two proteins to antagonize DNA-PK, but it is not known to target other DNA sensors, emphasizing the importance of this PRR in the response to infection in vivo

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

Standardized cross-cultural databases of the arts are critical to a balanced scientific understanding 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 Cantometrics 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 culture-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).Introduction Background The Global Jukebox and its data 1. The data 1.1. Datasets of the Global Jukebox 1.2. Comparison with other cross cultural datasets 1.3. Coded performance variables: Selection and reliability 1.4. Performance data sources 1.5. Selection of audio examples 1.6. Availability of audio recordings 1.7. Performance metadata 2. Sampling societies and links to other datasets 2.1. Sampling societies 2.2. Links to other cross-cultural datasets 3. Data curation, cleaning, and validation 4. Coding reliability 5. Is song style correlated with social complexity? An example of hypothesis testing using the Global Jukebox 5.1. Hypothesis testing with the Global Jukebox datasets 5.2. Methods 5.3 Results of reanalysis 5.4 Discussion 6. Ethics, rights and consent 7. Conclusio

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