PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/-) BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/-) BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists

Measures Matter: Scales for Adaptation, Cultural Distance, and Acculturation Orientation Revisited

Building upon existing measures, four new brief acculturation scales are presented, measuring sociocultural adaptation, psychological adaptation, perceived cultural distance, and acculturation orientation. Following good scale reliability in initial samples, the English scales were translated into nine different languages (Chinese, French, German, Italian, Japanese, Portuguese, Spanish, Thai, and Turkish). The translated scales were administered to a large sample of sojourners (N = 1,929), demonstrating good reliability and adequate structural equivalence across languages. In line with existing theory, sociocultural adaptation and psychological adaptation were positively correlated, and showed a negative association with perceived cultural distance. General measures of well-being were correlated with adaptation and distance, with better adaptation relating to higher well-being, and more distance relating to lower well-being. Acculturation orientation toward the home and host culture were measured separately and a weak negative correlation was found between the two, supporting their independence. Arguing against dichotomization, these subscales were analyzed as continuous variables. Regression analysis showed sojourners to be better adapted, if they were oriented more toward the host culture and less toward the home culture. These new scales are proposed as alternatives to existing measures

He Was not Alone: Bosman in Context

This chapter analyses the social, political, historical and economic context of the Bosman case. The chapter argues that Bosman needs to be understood as yet another stage of a continued process of commercialisation and transformation in European football. Football players fought to transform their employment conditions since the 1960s. Clubs questioned the legitimacy of UEFA to regulate European football and organise club competitions as they wanted a larger share of the commercial profits of the game. Finally, political institutions in Brussels started to exert pressure on football governing bodies to modify the international transfer system. The chapter argues that, taking these into account, major transformations in the governance and regulation structures of football were needed, and they would have happened even without the Bosman ruling. Consequently, Bosman cannot be seen, on its own, as the only cause of the transformation of modern football in Europe. Finally, the chapter dedicates some space to Jean Marc Bosman’s legal team composed by Luc Misson and Jean Louis Dupont. It was their legal expertise what made a challenge before the Belgian and European courts also possible

Advancing our understanding of the EU sports policy: the socio-cultural model of sports regulation and players’ agents

This paper explains the development of the socio-cultural dimension of the European Union (EU) sports policy over the course of the decade from 2005 to 2015. By adopting the theoretical lenses of the Advocacy Coalition Framework (ACF), the paper firstly offers a novel perspective on the belief systems of the members of the socio-cultural advocacy coalition that operates within the EU sports policy subsystem. A set of empirical policy core beliefs of the coalition actors reflecting their concerns regarding to sport’s integrity and economic welfare that affect its healthy development is presented and explained as the basic causes of the policy problem, i.e., threats that undermine sport’s specific characteristics. In this light, the paper then illustrates that the coalition members have perceived the issue of players’ agents, in particular problems in the activities of agents in European football, to be detrimental to the integrity of sport. As a result, the issue has been the subject of a considerable policy activity by the coalition actors with a view to establishing an alternative regulatory framework to effectively govern players’ agents. Consequently, the paper elucidates the evolving nature of the socio-cultural model of sports regulation that not only promotes the social role of sport in Europe but now also addresses the problems that affect its well-being and clear image. The paper’s principal method of investigation is based on the content analysis of official policy documents and statements of the coalition actors

Interleukin-1 Receptor-Associated Kinase-3 Is a Key Inhibitor of Inflammation in Obesity and Metabolic Syndrome

BACKGROUND: Visceral obesity is associated with the rising incidence of type 2 diabetes and metabolic syndrome. Low-grade chronic inflammation and oxidative stress synergize in obesity and obesity-induced disorders. OBJECTIVE: We searched a cluster of molecules that support interactions between these stress conditions in monocytes. METHODS: RNA expressions in blood monocytes of two independent cohorts comprising 21 and 102 obese persons and 46 age-matched controls were determined by microarray and independently validated by quantitative RT-PCR analysis. The effect of three-month weight loss after bariatric surgery was determined. The effect of RNA silencing on inflammation and oxidative stress was studied in human monocytic THP-1 cells. RESULTS: Interleukin-1 receptor-associated kinase-3 (IRAK3), key inhibitor of IRAK/NFκB-mediated chronic inflammation, is downregulated in monocytes of obese persons. Low IRAK3 was associated with high superoxide dismutase-2 (SOD2), a marker of mitochondrial oxidative stress. A comparable expression profile was also detected in visceral adipose tissue of the same obese subjects. Low IRAK3 and high SOD2 was associated with a high prevalence of metabolic syndrome (odds ratio: 9.3; sensitivity: 91%; specificity: 77%). By comparison, the odds ratio of high-sensitivity C-reactive protein, a widely used marker of systemic inflammation, was 4.3 (sensitivity: 69%; specificity: 66%). Weight loss was associated with an increase in IRAK3 and a decrease in SOD2, in association with a lowering of systemic inflammation and a decreasing number of metabolic syndrome components. We identified the increase in reactive oxygen species in combination with obesity-associated low adiponectin and high glucose and interleukin-6 as cause of the decrease in IRAK3 in THP-1 cells in vitro. CONCLUSION: IRAK3 is a key inhibitor of inflammation in association with obesity and metabolic syndrome. Our data warrant further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention

Heterogeneous mass distribution of the rubble-pile asteroid (101955) Bennu

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu’s surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu’s equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O’Keefe-Radzievskii-Paddack cycle or arising during Bennu’s accretion following the disruption of its parent body

Hemispherical differences in the shape and topography of asteroid (101955) Bennu

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu’s southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu’s history

A Novel Function of Apolipoprotein E: Upregulation of ATP-Binding Cassette Transporter A1 Expression

Despite the well known importance of apolipoprotein (Apo) E in cholesterol efflux, the effect of ApoE on the expression of ATP-binding cassette transporter A1 (ABCA1) has never been investigated. The objective of this study was to determine the effect of ApoE on ApoB-carrying lipoprotein-induced expression of ABCA1, a protein that mediates cholesterol efflux. Our data demonstrate that ApoB-carrying lipoproteins obtained from both wild-type and ApoE knockout mice induced ApoAI-mediated cholesterol efflux in mouse macrophages, which was associated with an enhanced ABCA1 promoter activity, and an increased ABCA1 mRNA and protein expression. In addition, these lipoproteins increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter. However, all these inductions were significantly diminished in cells treated with ApoE-free lipoproteins, when compared to those treated with wild-type lipoproteins. Enrichment with human ApoE3 reversed the reduced inducibility of ApoE-free lipoproteins. Moreover, we observed that inhibition of Sp1 DNA-binding by mithramycin A diminished ABCA1 expression and ApoAI-mediated cholesterol efflux induced by ApoB-carrying lipoproteins, and that mutation of the Sp1-binding motif in the ABCA1 promoter region diminished ApoB-carrying lipoprotein-induced ABCA1 promoter activity. Collectively, these data suggest that ApoE associated with ApoB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and that induction of Sp1 phosphorylation is a mechanism by which ApoE upregulates ABCA1 expression

The role of psychologists in international migration research: complementing other expertise and an interdisciplinary way forward

This research note addresses the current and potential future role of psychologists in the study of international migration. It reviews ways in which psychologists have contributed to the study of migration, as well as ways in which psychological scholarship could be integrated with work from other social science fields. Broadly, the note discusses four major contributions that psychology brings to the study of international migration—studying migrants’ internal psychological experiences, incorporating a developmental perspective, conducting experimental studies, and integrating across levels of analysis. Given the position of psychology as a ‘hub science’ connecting more traditional social sciences with health and medical sciences, we argue for a more prominent role for psychologists within the study of international migration. Such a role is intended to complement the roles of other social scientists and to create a more interdisciplinary way forward for the field of migration studies. The research note concludes with an agenda for further scholarship on migration.Development Psychopathology in context: clinical setting