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BACKGROUND: P2Y(6), a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6) deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6) receptors, showed that exogenous expression of P2Y(6) induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6)-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6) and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6) in atherosclerotic lesion development, we used P2Y(6)-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6) receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6)xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6) deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6) receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6) deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6) in vascular disease pathophysiologies, such as aneurysm formation.

BACKGROUND: Chronic glucocorticoid excess has been linked to increased atherosclerosis and general cardiovascular risk in humans. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) increases active glucocorticoid levels within tissues by catalyzing the conversion of cortisone to cortisol. Pharmacological inhibition of 11βHSD1 has been shown to reduce atherosclerosis in murine models. However, the cellular and molecular details for this effect have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: To examine the role of 11βHSD1 in atherogenesis, 11βHSD1 knockout mice were created on the pro-atherogenic apoE⁻/⁻ background. Following 14 weeks of Western diet, aortic cholesterol levels were reduced 50% in 11βHSD1⁻/⁻/apoE⁻/⁻ mice vs. 11βHSD1⁺/⁺/apoE⁻/⁻ mice without changes in plasma cholesterol. Aortic 7-ketocholesterol content was reduced 40% in 11βHSD1⁻/⁻/apoE⁻/⁻ mice vs. control. In the aortic root, plaque size, necrotic core area and macrophage content were reduced ∼30% in 11βHSD1⁻/⁻/apoE⁻/⁻mice. Bone marrow transplantation from 11βHSD1⁻/⁻/apoE⁻/⁻ mice into apoE⁻/⁻ recipients reduced plaque area 39-46% in the thoracic aorta. In vivo foam cell formation was evaluated in thioglycollate-elicited peritoneal macrophages from 11βHSD1⁺/⁺/apoE⁻/⁻ and 11βHSD1⁻/⁻/apoE⁻/⁻ mice fed a Western diet for ∼5 weeks. Foam cell cholesterol levels were reduced 48% in 11βHSD1⁻/⁻/apoE⁻/⁻ mice vs. control. Microarray profiling of peritoneal macrophages revealed differential expression of genes involved in inflammation, stress response and energy metabolism. Several toll-like receptors (TLRs) were downregulated in 11βHSD1⁻/⁻/apoE⁻/⁻ mice including TLR 1, 3 and 4. Cytokine release from 11βHSD1⁻/⁻/apoE⁻/⁻-derived peritoneal foam cells was attenuated following challenge with oxidized LDL. CONCLUSIONS: These findings suggest that 11βHSD1 inhibition may have the potential to limit plaque development at the vessel wall and regulate foam cell formation independent of changes in plasma lipids. The diminished cytokine response to oxidized LDL stimulation is consistent with the reduction in TLR expression and suggests involvement of 11βHSD1 in modulating binding of pro-atherogenic TLR ligands.

Objective: People's psychological tendencies are attuned to their sociocultural context and culture-specific ways of being, feeling, and thinking are believed to assist individuals in successfully navigating their environment. Supporting this idea, a stronger "fit" with one's cultural environment has often been linked to positive psychological outcomes. The current research expands the cultural, conceptual, and methodological space of cultural fit research by exploring the link between well-being and honor, a central driver of social behavior in the Mediterranean region., Method: Drawing on a multi-national sample from eight countries circum-Mediterranean (N = 2257), we examined the relationship between cultural fit in honor and well-being at the distal level (fit with one's perceived society) using response surface analysis (RSA) and at the proximal level (fit with one's university gender group) using profile analysis., Results: We found positive links between fit and well-being in both distal (for some, but not all, honor facets) and proximal fit analyses (across all honor facets). Furthermore, most fit effects in the RSA were complemented with positive level effects of the predictors, with higher average honor levels predicting higher well-being., Conclusions: Our findings highlight the interplay between individual and environmental factors in honor as well as the important role honor plays in well-being in the Mediterranean region., (© 2022 The Authors. Journal of Personality published by Wiley Periodicals LLC.)

Academic Abstract: Social psychology's disconnect from the vital and urgent questions of people's lived experiences reveals limitations in the current paradigm. We draw on a related perspective in social psychology 1 -the sociocultural approach-and argue how this perspective can be elaborated to consider not only social psychology as a historical science but also social psychology of and for world-making. This conceptualization can make sense of key theoretical and methodological challenges faced by contemporary social psychology. As such, we describe the ontology, epistemology, ethics, and methods of social psychology of and for world-making. We illustrate our framework with concrete examples from social psychology. We argue that reconceptualizing social psychology in terms of world-making can make it more humble yet also more relevant, reconnecting it with the pressing issues of our time., Public Abstract: We propose that social psychology should focus on "world-making" in two senses. First, people are future-oriented and often are guided more by what could be than what is. Second, social psychology can contribute to this future orientation by supporting people's world-making and also critically reflecting on the role of social psychological research in world-making. We unpack the philosophical assumptions, methodological procedures, and ethical considerations that underpin a social psychology of and for world-making. Social psychological research, whether it is intended or not, contributes to the societies and cultures in which we live, and thus it cannot be a passive bystander of world-making. By embracing social psychology of and for world-making and facing up to the contemporary societal challenges upon which our collective future depends will make social psychology more humble but also more relevant., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Social science research has highlighted "honor" as a central value driving social behavior in Mediterranean societies, which requires individuals to develop and protect a sense of their personal self-worth and their social reputation, through assertiveness, competitiveness, and retaliation in the face of threats. We predicted that members of Mediterranean societies may exhibit a distinctive combination of independent and interdependent social orientation, self-construal, and cognitive style, compared to more commonly studied East Asian and Anglo-Western cultural groups. We compared participants from eight Mediterranean societies (Spain, Italy, Greece, Turkey, Cyprus [Turkish Cypriot and Greek Cypriot communities], Lebanon, Egypt) to participants from East Asian (Korea, Japan) and Anglo-Western (the United Kingdom, the United States) societies, using six implicit social orientation indicators, an eight-dimensional self-construal scale, and four cognitive style indicators. Compared with both East Asian and Anglo-Western samples, samples from Mediterranean societies distinctively emphasized several forms of independence (relative intensity of disengaging [vs. engaging] emotions, happiness based on disengaging [vs. engaging] emotions, dispositional [vs. situational] attribution style, self-construal as different from others, self-directed, self-reliant, self-expressive, and consistent) and interdependence (closeness to in-group [vs. out-group] members, self-construal as connected and committed to close others). Our findings extend previous insights into patterns of cultural orientation beyond commonly examined East-West comparisons to an understudied world region. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Transforming long-term conflicts into peaceful intergroup relations is one of the most difficult challenges for humanity. Such meaningful social changes are often driven by young people. But do young people living in contexts of long-term conflicts believe that change is even possible? In a series of six studies (N total  = 119,671) over two decades and across two unrelated intractable conflicts in Israel/Palestine and Cyprus, we found that younger (compared to older) generations from both respective rival groups have less hope for peace, and consequently less conciliatory attitudes. We also show that this gradual improvement of peace-promoting emotions and attitudes with increasing age can be experimentally accelerated in young people through a virtual reality-based aging simulation. These findings provide a new perspective on the fundamental question of why long-term conflicts are so difficult to resolve and highlight the importance of instilling hope in young generations to advance peace processes., (© 2023. The Author(s).)

It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (N total  = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions-warmth and competence-plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges., (© 2022. The Author(s).)

Background In sepsis, circulating cytokines and lipopolysaccharide elicit mitochondrial dysfunction and cardiomyopathy, a major cause of morbidity and mortality with this condition. Emerging research places the PHB1 (lipid raft protein prohibitin-1) at the nexus of inflammation, metabolism, and oxidative stress. PHB1 has also been reported in circulation, though its function in this compartment is completely unknown. Methods and Results Using a wide-ranging approach across multiple in vitro and in vivo models, we interrogated the functional role of intracellular and circulating PHB1 in the heart during sepsis, and elucidated some of the mechanisms involved. Upon endotoxin challenge or sepsis induction in rodent models, PHB1 translocates from mitochondria to nucleus in cardiomyocytes and is secreted into the circulation from the liver in a manner dependent on nuclear factor (erythroid-derived 2)-like 2, a key transcriptional regulator of the antioxidant response. Overexpression or treatment with recombinant human PHB1 enhances the antioxidant/anti-inflammatory response and protects HL-1 cardiomyocytes from mitochondrial dysfunction and toxicity from cytokine stress. Importantly, administration of recombinant human PHB1 blunted inflammation and restored cardiac contractility and ATP production in mice following lipopolysaccharide challenge. This cardioprotective, anti-inflammatory effect of recombinant human PHB1 was determined to be independent of nuclear factor (erythroid-derived 2)-like 2, but partially dependent on PI3K/AKT  signaling in the heart. Conclusions These findings reveal a previously unknown cardioprotective effect of PHB1 during sepsis, and illustrate a pro-survival, protective role for PHB1 in the circulation. Exploitation of circulating PHB1 as a biomarker and/or therapeutic could have widespread benefit in the clinical management of sepsis and other severe inflammatory disorders.

Exposure to ozone (O3) induces lung injury, pulmonary inflammation, and alters lipid metabolism. During tissue inflammation, specialized pro-resolving lipid mediators (SPMs) facilitate the resolution of inflammation. SPMs regulate the pulmonary immune response during infection and allergic asthma; however, the role of SPMs in O3-induced pulmonary injury and inflammation is unknown. We hypothesize that O3 exposure induces pulmonary inflammation by reducing SPMs. To evaluate this, male C57Bl/6J mice were exposed to filtered air (FA) or 1 ppm O3 for 3 h and necropsied 24 h after exposure. Pulmonary injury/inflammation was determined by bronchoalveolar lavage (BAL) differentials, protein, and lung tissue cytokine expression. SPMs were quantified by liquid chromatography tandem mass spectrometry and SPM receptors leukotriene B4 receptor 1 (BLT-1), formyl peptide receptor 2 (ALX/FPR2), chemokine-like receptor 1 (ChemR23), and SPM-generating enzyme (5-LOX and 12/15-LOX) expression were measured by real time PCR. 24 h post-O3 exposure, BAL PMNs and protein content were significantly increased compared to FA controls. O3-induced lung inflammation was associated with significant decreases in pulmonary SPM precursors (14-HDHA, 17-HDHA), the SPM PDX, and in pulmonary ALX/FPR2, ChemR23, and 12/15-LOX expression. Exogenous administration of 14-HDHA, 17-HDHA, and PDX 1 h prior to O3 exposure rescued pulmonary SPM precursors/SPMs, decreased proinflammatory cytokine and chemokine expression, and decreased BAL macrophages and PMNs. Taken together, these data indicate that O3-mediated SPM reductions may drive O3-induced pulmonary inflammation.

Two hundred and sixty-four children aged 6.5-7.5 years (first graders) took part in a pre-test, interaction, and post-test experiment working on a spatial transformation task known as the 'village task'. Cognitive progress was assessed by pre- to post-test gains in both an immediate and delayed post-test in dyads and individual participants as a control. The results indicate clear links between particular pair types with both communication processes and with learning and cognitive developmental outcomes. The present study demonstrates that gender can act as a source of status asymmetry in peer interaction to influence communication, learning, and cognitive development in same- and mixed-sex dyads.

Although intergroup contact is one of the most prominent interventions to reduce prejudice, the generalization of contact effects is still a contentious issue. This research further examined the rarely studied secondary transfer effect (STE; Pettigrew, 2009), by which contact with a primary outgroup reduces prejudice toward secondary groups that are not directly involved in the contact. Across 3 cross-sectional studies conducted in Cyprus (N = 1,653), Northern Ireland (N = 1,973), and Texas (N = 275) and 1 longitudinal study conducted in Northern Ireland (N = 411), the present research sought to systematically rule out alternative accounts of the STE and to investigate 2 potential mediating mechanisms (ingroup reappraisal and attitude generalization). Results indicated that, consistent with the STE, contact with a primary outgroup predicts attitudes toward secondary outgroups, over and above contact with the secondary outgroup, socially desirable responding, and prior attitudes. Mediation analyses found strong evidence for attitude generalization but only limited evidence for ingroup reappraisal as an underlying process. Two out of 3 tests of a reverse model, where contact with the secondary outgroup predicts attitudes toward the primary outgroup, provide further evidence for an indirect effect through attitude generalization. Theoretical and practical implications of these results are discussed, and directions for future research are identified.

In this paper I draw on Piaget and Habermas to underline the importance of the theoretical distinction between social relations of constraint and social relations of cooperation for reflecting upon inter-institutional projects. I argue that the socio-cultural approach to collaboration has some important limitations that restrict ideological critic and emancipatory research. The limitations of this approach can be located in its epistemological assumptions, a homogenized notion of culture and a weakness in articulating the intrapersonal, inter-personal, inter-group/positional and social representational/ideological levels of analysis. As an empirical example of this I discuss the Sloan centres for family research.