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

Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study

T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a match or near-match between the epitope induced by vaccination and the infecting viral strain. We compared the frequency and specificity of the CTL epitope responses elicited by the replication-defective Ad5 gag/pol/nef vaccine used in the Step trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. Among vaccinees with detectable 15-mer peptide pool ELISpot responses, there was a median of four (one Gag, one Nef and two Pol) CD8 epitopes per vaccinee detected by 9-mer peptide ELISpot assay. Importantly, frequency analysis of the mapped epitopes indicated that there was a significant skewing of the T cell response; variable epitopes were detected more frequently than would be expected from an unbiased sampling of the vaccine sequences. Correspondingly, the most highly conserved epitopes in Gag, Pol, and Nef (defined by presence in >80% of sequences currently in the Los Alamos database www.hiv.lanl.gov) were detected at a lower frequency than unbiased sampling, similar to the frequency reported for responses to natural infection, suggesting potential epitope masking of these responses. This may be a generic mechanism used by the virus in both contexts to escape effective T cell immune surveillance. The disappointing results of the Step trial raise the bar for future HIV vaccine candidates. This report highlights the bias towards less-conserved epitopes present in the same vaccine used in the Step trial. Development of vaccine strategies that can elicit a greater breadth of responses, and towards conserved regions of the genome in particular, are critical requirements for effective T-cell based vaccines against HIV-1

Definition of the viral targets of protective HIV-1-specific T cell responses

<p>Abstract</p> <p>Background</p> <p>The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.</p> <p>Methods</p> <p>Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.</p> <p>Results</p> <p>For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.</p> <p>Conclusions</p> <p>The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.</p

HLA-restricted immune responses have driven the evolution of HIV-1 clades

Background. HIV mutates to escape selective pressure from antiretroviral medications and HLA-mediated immune responses. Escape mutations can, but do not necessarily, revert to “wild type” (WT) when the selective pressure is withdrawn. Worldwide, HIV has diversified into numerous clades and recombinant forms, and these variations generally follow geopolitical boundaries. Genetically similar human populations also follow these boundaries, so we hypothesized that population HLA has driven HIV evolution and its diversification into the clades. Methods. HIV isolates from 2 HLA-typed cohorts of antiretroviral-naïve patients were analyzed; these isolates included 107 sequences from Caucasian patients in Australia infected with clade B, and 96 from patients in Durban, Africa, infected with clade C. Polymorphism rates were calculated for each amino acid residue in p24 and p17. Associations between HLA and each amino acid residue (comparing consensus vs all nonconsensus) were quantified using multiple logistic regression models with stepwise selection of HLA class I genotype as covariates. Consensus protein sequences for clades A, B, C, D, F, and G obtained from the Los Alamos HIV database were aligned and compared with the locations of polymorphism and HLA association. Results. In p24 and p17, amino acid polymorphism (> 10% of the isolates differed from consensus) occurred at 50 and 56 residues in the Australian and African sequences, respectively. Of these, 33 were in common. Most of the alternative residues found in the Australian and African cohorts were the consensus amino acids for clades other than B and C, respectively. In each cohort, we found 38 residues with significant (p < 0.05) positive and/or negative associations between HLA and sequence polymorphism. The consensus protein sequences for clades A, B, C, D, F, and G differed at 79 residues. In both cohorts almost all of the polymorphic residues—42 (84%) for Australia and 46 (82%) for Africa—and HLA associations—32 (84%) for Australia and 30 (79%) for Africa—occurred at positions where the clade consensus sequences differed. These distributions were highly significant (Fisher p < 0.0001 for both). Conclusions. After introduction of an HIV variant into a host, CTL-mediated immune pressure drives viral evolution within that host. At a population level we propose that the evolution of clades similarly reflects both founder effects and the selective pressures provided by the population HLA distribution

Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities

Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations

Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys

The worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development. Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity. Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1