The association between political orientation and political knowledge in 45 nations.

Political knowledge is crucial for well-functioning democracies, with most scholars assuming that people at the political extremes are more knowledgeable than those at the center. Here, we adopt a data-driven approach to examine the relationship between political orientation and political knowledge by testing a series of polynomial curves in 45 countries (N = 63,544), spread over 6 continents. Contrary to the dominant perspective, we found no evidence that people at the political extremes are the most knowledgeable about politics. Rather, the most common pattern was a fourth-degree polynomial association in which those who are moderately left-wing and right-wing are more knowledgeable than people at the extremes and center of the political spectrum. This pattern was especially, though not exclusively, prevalent in Western countries. We conclude that the relationship between political orientation and political knowledge is more context-dependent and complex than assumed, and caution against (implicit) universal conclusions in social sciences.

Rationally blind? Rationality polarizes policy support for colour blindness versus multiculturalism.

Do White Americans prefer society to be 'colour-blind' by rising above racial identities, or 'multicultural' by openly discussing and considering them? We developed an ideology-rationality model to understand support for these diversity perspectives. Specifically, since people endorse a diversity perspective in line with their ideological values, we hypothesized that conservatism is related to a relative preference for colour blindness over multiculturalism. However, since colour blindness and multiculturalism are complex and multi-layered ideologies, we further hypothesized that the relationship between conservatism and a preference for colour blindness over multiculturalism is especially pronounced under higher levels of rationality. Results confirmed the hypotheses, either when rationality was operationalized within a dual process theory (Study 1, N = 496) or experimentally induced within a tripartite model of cognition (Study 2, N = 497). Higher levels of rationality guided White Americans high in conservatism towards a stronger preference for colour-blindness, but those low in conservatism towards a stronger preference for multiculturalism. These results suggest that among White Americans the endorsement of colour blindness versus multiculturalism stems from the interplay between ideological orientation and rationality and that rational considerations about racial policies may further divide rather than unify along ideological lines.

Effects of absolute levels of neighbourhood ethnic diversity vs. changes in neighbourhood diversity on prejudice: Moderation by individual differences in personality.

This paper examines drivers of prejudicial attitudes among adults in the UK, focusing on the interaction between ethnic out-group size and personality traits. Leveraging data from the National Child Development Study (NCDS), we use two survey waves carried out in 2000 and 2008, just before and after the EU enlargement policy that drove a wave of immigration in the UK. We test the extent to which personality traits moderate the relationship between both absolute levels and changes in ethnic diversity at the local level, respectively, and prejudice. Key findings suggest that personality traits, in particular one's agreeableness, are important for conditioning how the proportion of non-white British in one's neighbourhood affects out-group attitudes. We observe a tendency towards polarisation in prejudicial attitudes between low-/high-agreeableness residents as their neighbourhoods become more diverse. These findings have important implications for theorising how contextual and individual characteristics jointly affect intergroup relations.

epiAneufinder identifies copy number alterations from single-cell ATAC-seq data.

Single-cell open chromatin profiling via scATAC-seq has become a mainstream measurement of open chromatin in single-cells. Here we present epiAneufinder, an algorithm that exploits the read count information from scATAC-seq data to extract genome-wide copy number alterations (CNAs) for individual cells, allowing the study of CNA heterogeneity present in a sample at the single-cell level. Using different cancer scATAC-seq datasets, we show that epiAneufinder can identify intratumor clonal heterogeneity in populations of single cells based on their CNA profiles. We demonstrate that these profiles are concordant with the ones inferred from single-cell whole genome sequencing data for the same samples. EpiAneufinder allows the inference of single-cell CNA information from scATAC-seq data, without the need of additional experiments, unlocking a layer of genomic variation which is otherwise unexplored.

Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data.

BACKGROUND: Expression quantitative trait loci (eQTL) studies show how genetic variants affect downstream gene expression. Single-cell data allows reconstruction of personalized co-expression networks and therefore the identification of SNPs altering co-expression patterns (co-expression QTLs, co-eQTLs) and the affected upstream regulatory processes using a limited number of individuals. RESULTS: We conduct a co-eQTL meta-analysis across four scRNA-seq peripheral blood mononuclear cell datasets using a novel filtering strategy followed by a permutation-based multiple testing approach. Before the analysis, we evaluate the co-expression patterns required for co-eQTL identification using different external resources. We identify a robust set of cell-type-specific co-eQTLs for 72 independent SNPs affecting 946 gene pairs. These co-eQTLs are replicated in a large bulk cohort and provide novel insights into how disease-associated variants alter regulatory networks. One co-eQTL SNP, rs1131017, that is associated with several autoimmune diseases, affects the co-expression of RPS26 with other ribosomal genes. Interestingly, specifically in T cells, the SNP additionally affects co-expression of RPS26 and a group of genes associated with T cell activation and autoimmune disease. Among these genes, we identify enrichment for targets of five T-cell-activation-related transcription factors whose binding sites harbor rs1131017. This reveals a previously overlooked process and pinpoints potential regulators that could explain the association of rs1131017 with autoimmune diseases. CONCLUSION: Our co-eQTL results highlight the importance of studying context-specific gene regulation to understand the biological implications of genetic variation. With the expected growth of sc-eQTL datasets, our strategy and technical guidelines will facilitate future co-eQTL identification, further elucidating unknown disease mechanisms.

Intergroup contact is reliably associated with reduced prejudice, even in the face of group threat and discrimination.

Intergroup contact provides a reliable means of reducing prejudice. Yet, critics suggested that its efficacy is undermined, even eliminated, under certain conditions. Specifically, contact may be ineffective in the face of threat, especially to (historically) advantaged groups, and discrimination, experienced especially by (historically) disadvantaged groups. We considered perceived intergroup threat and perceived discrimination as potential moderators of the effect of contact on prejudice. Two meta-analyses of correlational data from 34 studies (totaling 63,945 respondents-drawn from 67 subsamples across 19 countries) showed that contact was associated with decreased prejudice and increased out-group positivity, in cross-sectional and longitudinal designs, among advantaged and disadvantaged group members, and in both Western, Educated, Industrialized, Rich, and Democratic (WEIRD) and non-WEIRD contexts. Both perceived threat and perceived discrimination moderated the contact-attitude association, but in an unanticipated direction. Indeed, contact's beneficial effects were at least as strong among individuals high (r = .19) as among individuals low (r = .18) in perceived threat. Similarly, the effects of contact were at least as strong among those high (r = .23) as among those low (r = .20) in perceived discrimination. We conclude that contact is effective for promoting tolerant societies because it is effective even among subpopulations where achieving that goal might be most challenging. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Selective exposure bias predicts views on diversity over time.

Despite growing diversity, many individuals do not support it, posing a challenge to the successful functioning of societies, institutions, and organizations. We investigated the role of the selective exposure bias on diversity beliefs. In a large-scale nationally representative Spanish sample (N = 2,297), we conducted a time-lagged experiment with two time points 5 months apart in which we offered participants a monetary incentive to (allegedly) read attitude contradictory versus conforming information about societal support for refugees. The selective exposure bias asymmetrically predicted future diversity beliefs. Among individuals with a positive intergroup orientation, the selective exposure bias did not predict future diversity beliefs. However, among individuals with a negative intergroup orientation, the selective exposure bias predicted lower pro-diversity beliefs over time, over and above initial pro-diversity beliefs and ideological dispositions. These findings suggest that the absence of pro-diversity beliefs partly originates from a cognitive bias, holding critical implications for policymakers seeking to improve intergroup relations.

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics.

In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such an endothelial compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays.

Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.

South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10-8 to 5.2 × 10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.

Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function.

We determined the relationships between DNA sequence variation and DNA methylation using blood samples from 3,799 Europeans and 3,195 South Asians. We identify 11,165,559 SNP-CpG associations (methylation quantitative trait loci (meQTL), P < 10-14), including 467,915 meQTL that operate in trans. The meQTL are enriched for functionally relevant characteristics, including shared chromatin state, High-throuhgput chromosome conformation interaction, and association with gene expression, metabolic variation and clinical traits. We use molecular interaction and colocalization analyses to identify multiple nuclear regulatory pathways linking meQTL loci to phenotypic variation, including UBASH3B (body mass index), NFKBIE (rheumatoid arthritis), MGA (blood pressure) and COMMD7 (white cell counts). For rs6511961 , chromatin immunoprecipitation followed by sequencing (ChIP-seq) validates zinc finger protein (ZNF)333 as the likely trans acting effector protein. Finally, we used interaction analyses to identify population- and lineage-specific meQTL, including rs174548 in FADS1, with the strongest effect in CD8+ T cells, thus linking fatty acid metabolism with immune dysregulation and asthma. Our study advances understanding of the potential pathways linking genetic variation to human phenotype.

Reduced thrombogenicity of surface-treated Nitinol implants steered by altered protein adsorption.

Blood-contacting medical implants made of Nitinol and other titanium alloys, such as neurovascular flow diverters and peripheral stents, have the disadvantage of being highly thrombogenic. This makes the use of systemic (dual) anti-platelet/anticoagulant therapies inevitable with related risks of device thrombosis, bleeding and other complications. Meeting the urgent clinical demand for a less thrombogenic Nitinol surface, we describe here a simple treatment of standard, commercially available Nitinol that renders its surface ultra-hydrophilic and functionalized with phosphate ions. The efficacy of this treatment was assessed by comparing standard and surface-treated Nitinol disks and braids, equivalent to flow diverters. Static and dynamic (Chandler loop) blood incubation tests showed a drastic reduction of thrombus formation on treated devices. Surface chemistry and proteomic analysis indicated a key role of phosphate and calcium ions in steering blood protein adsorption and avoiding coagulation cascade activation and platelet adhesion. A good endothelialization of the surface confirmed the biocompatibility of the treated surface. STATEMENT OF SIGNIFICANCE: Titanium alloys such as Nitinol are biocompatible and show favorable mechanical properties, which led to their widespread use in medical implants. However, in contact with blood their surface triggers the activation of the intrinsic coagulation cascade, which may result in catastrophic thrombotic events. The presented results showed that a phosphate functionalization of the titanium oxide surface suppresses the activation of both coagulation cascade and platelets, avoiding the subsequent formation of a blood clot. This novel approach has therefore a great potential for mitigating the risks associated to either thrombosis or bleeding complications (due to systemic anticoagulation) in patients with cardiovascular implants.

Dynamic contact effects: Individuals' positive and negative contact history influences intergroup contact effects in a behavioral game.

Positive contact between members of different groups reduces prejudice and increases cooperation, findings known as intergroup contact effects. Yet in real-world settings not only positive, but also negative intergroup contact occurs, which have opposing effects. To date little is known about whether and how an individual's valenced history of intergroup contact influences contact effects and how this dynamic change happens during specific instances of intergroup contact. A pilot study examined the psychological impact of a novel paradigm to assess intergroup contact using a behavioral game. We then conducted two studies, which allowed us to observe a sequence of up to 23 in- and outgroup interactions and their behavioral outcomes in a continuous prisoner's dilemma behavioral game (N = 116, 2,668 interactions; N = 89, 1,513 interactions). As expected, participants showed a clear ingroup bias in expectations and cooperation. Furthermore, the quality of contact history moderated contact effects. Specifically, intergroup contact following a positive history of intergroup contact had a stronger effect on intergroup expectations than contact following a negative history thereof. Findings are discussed in view of the importance of considering the valenced history of intergroup contact, as well as new research questions on intergroup contact that can be addressed with this novel contact paradigm. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comprehensive quantitative characterization of the human term amnion proteome.

The loss of fetal membrane (FM) integrity and function at an early time point during pregnancy can have devastating consequences for the fetus and the newborn. However, biomaterials for preventive sealing and healing of FMs are currently non-existing, which can be partly attributed to the current fragmentary knowledge of FM biology. Despite recent advances in proteomics analysis, a robust and comprehensive description of the amnion proteome is currently lacking. Here, by an optimized protein sample preparation and offline fractionation before liquid chromatography coupled to mass spectrometry (LC-MS) analysis, we present a characterization of the healthy human term amnion proteome, which covers more than 40% of the previously reported transcripts in similar RNA sequencing datasets and, with more than 5000 identifications, greatly outnumbers previous reports. Together, beyond providing a basis for the study of compromised and preterm ruptured FMs, this comprehensive human amnion proteome is a stepping-stone for the development of novel healing-inducing biomaterials. The proteomic dataset has been deposited in the ProteomeXchange Consortium with the identifier PXD019410.

scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies.

Single cell RNA-seq has revolutionized transcriptomics by providing cell type resolution for differential gene expression and expression quantitative trait loci (eQTL) analyses. However, efficient power analysis methods for single cell data and inter-individual comparisons are lacking. Here, we present scPower; a statistical framework for the design and power analysis of multi-sample single cell transcriptomic experiments. We modelled the relationship between sample size, the number of cells per individual, sequencing depth, and the power of detecting differentially expressed genes within cell types. We systematically evaluated these optimal parameter combinations for several single cell profiling platforms, and generated broad recommendations. In general, shallow sequencing of high numbers of cells leads to higher overall power than deep sequencing of fewer cells. The model, including priors, is implemented as an R package and is accessible as a web tool. scPower is a highly customizable tool that experimentalists can use to quickly compare a multitude of experimental designs and optimize for a limited budget.

Adolescent development of interethnic attitudes following a social intervention to increase intergroup contact: The moderating role of affective forecasting.

This longitudinal, quasi-experimental field study investigated affective forecasting as a moderator of positive intergroup contact effects among adolescents. We also examined a novel mediating mechanism that underlies this effect, namely accuracy of perceived outgroup willingness for intergroup contact. Three annual waves of survey data were used from 1,169 adolescents (Mage = 13.88 at Wave 1; 50% girls; 66% White British, 44% Asian British) whose schools were merged, in a unique intervention that resulted in one school where ethnic groups were evenly mixed (i.e., balanced school) and two White British majority schools (i.e., majority skewed schools). Results showed that positive intergroup contact and attitudes improved more in the balanced school than in the majority skewed schools. In all schools, change in adolescents' positive intergroup contact predicted change in positive intergroup attitudes indirectly via (a) increased accuracy of perceived outgroup willingness for contact and (b) reduced intergroup anxiety. Indirect effects via accuracy of perceived contact willingness were stronger for adolescents who made more negative affective forecasts than for other adolescents. These moderated mediation effects were stronger in the balanced school than in the majority skewed schools. Thus, more balanced ethnic mixing in schools seemed to directly enhance positive intergroup relations and attitudes for all adolescents, but to particularly benefit adolescents who made more negative affective forecasts about positive contact before the school merger. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3.

Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface. Mutation of H3K36 to arginine or alanine inhibits H3K27 methylation by PRC2 on nucleosomes in vitro. Accordingly, Drosophila H3K36A and H3K36R mutants show reduced levels of H3K27me3 and defective Polycomb repression of HOX genes. The relay of interactions between EZH2, the nucleosomal DNA and the H3 N-terminus therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in transcriptionally active chromatin.

Strategic experimentation with asymmetric players.

We examine a two-player game with two-armed exponential bandits à la (Keller et al. in Econometrica 73:39-68, 2005), where players operate different technologies for exploring the risky option. We characterise the set of Markov perfect equilibria and show that there always exists an equilibrium in which the player with the inferior technology uses a cut-off strategy. All Markov perfect equilibria imply the same amount of experimentation but differ with respect to the expected speed of the resolution of uncertainty. If and only if the degree of asymmetry between the players is high enough, there exists a Markov perfect equilibrium in which both players use cut-off strategies. Whenever this equilibrium exists, it welfare dominates all other equilibria. This contrasts with the case of symmetric players, where there never exists a Markov perfect equilibrium in cut-off strategies.

When good for business is not good enough: Effects of pro-diversity beliefs and instrumentality of diversity on intergroup attitudes.

Instrumentality-based pro-diversity beliefs (i.e., beliefs that diverse groups outperform homogenous groups in terms of group functioning) have been shown to improve intergroup attitudes. However, such valuing of diversity due to its expected instrumentality holds the risk that outgroups may be devalued in situations when diversity ends up being detrimental to group functioning. Across four experiments, we studied the interplay between instrumentality-based pro-diversity beliefs, actual instrumentality of ethnic diversity, and outgroup attitudes. Our results do not reveal a robust interaction effect between instrumentality-based pro-diversity beliefs and actual instrumentality of diverse groups. Some evidence, however, supports the assumption that instrumentality-based pro-diversity beliefs yielded a weaker positive or even a negative effect on ethnic outgroup attitudes when ethnic diversity was perceived as non-instrumental (i.e., when diversity was perceived as having a negative impact on group functioning). Theoretical contributions, practical implications, and directions for future research are discussed.