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With a growing Muslim population, many European countries need to integrate Muslims into their societies. One aspect that can hinder successful integration are substantial differences in human values. This is because such values are consequential for attitudes as well as behavior. We compare basic human values between Muslim immigrants and non-Muslim natives in four European countries with distinct immigration histories and integration politics: Belgium, France, Germany, and Sweden. For most insightful comparisons, we contrast values of Muslim immigrants with those of Christian natives as well as those of non-religious natives. We employ data of more than 50,000 individuals based on the first eight waves of the European Social Survey. Our findings reveal significant differences in value priorities between Muslims, Christians and non-religious individuals in all four countries. Amongst other things, Muslim immigrants score particularly high in conservation values (security and tradition/conformity). At the same time, they also score higher in self-transcendence values (benevolence as well as universalism). While many of these findings are in line with theory and previous research, the higher score in universalism is unexpected. A potential explanation is the combination of religious traditionalism and discrimination experiences. In other words, religious traditions are associated with more conservative views, but being subject to marginalization can still result in an appreciation of equal opportunities. We find only limited support for differences in hedonism. Religiosity correlates with values of tradition/conformity for Muslim immigrants as well as for Christian natives. Thus, accounting for religiosity renders differences in these values between Muslims and other groups statistically insignificant. While most of these findings hold in all countries, differences are most pronounced in Sweden and lower in the other three countries, which is also true after accounting for differences in socio-economic status and religiosity between the three groups. This suggests that a combination of a country's history of diversity and national integration policies either encourages the convergence of values or leads to a solidification of value differences between groups. We discuss these political and social implications of our findings.
Ryanodine receptor 1 (RyR1) mediates excitation–contraction coupling by releasing Ca2+ from sarcoplasmic reticulum (SR) to the cytoplasm of skeletal muscle cells. RyR1 activation is regulated by several proteins from both the cytoplasm and lumen of the SR. Here, we report the structure of RyR1 from native SR membranes in closed and open states. Compared to the previously reported structures of purified RyR1, our structure reveals helix‐like densities traversing the bilayer approximately 5 nm from the RyR1 transmembrane domain and sarcoplasmic extensions linking RyR1 to a putative calsequestrin network. We document the primary conformation of RyR1 in situ and its structural variations. The activation of RyR1 is associated with changes in membrane curvature and movement in the sarcoplasmic extensions. Our results provide structural insight into the mechanism of RyR1 in its native environment.
The sphingolipid sphingosine‐1‐phosphate (S1P) fulfills distinct functions in immune cell biology via binding to five G protein‐coupled receptors. The immune cell‐specific sphingosine‐1‐phosphate receptor 4 (S1pr4) was connected to the generation of IL‐17‐producing T cells through regulation of cytokine production in innate immune cells. Therefore, we explored whether S1pr4 affected imiquimod‐induced murine psoriasis via regulation of IL‐17 production. We did not observe altered IL‐17 production, although psoriasis severity was reduced in S1pr4‐deficient mice. Instead, ablation of S1pr4 attenuated the production of CCL2, IL‐6, and CXCL1 and subsequently reduced the number of infiltrating monocytes and granulocytes. A connection between S1pr4, CCL2, and Mϕ infiltration was also observed in Zymosan‐A induced peritonitis. Boyden chamber migration assays functionally linked reduced CCL2 production in murine skin and attenuated monocyte migration when S1pr4 was lacking. Mechanistically, S1pr4 signaling synergized with TLR signaling in resident Mϕs to produce CCL2, likely via the NF‐κB pathway. We propose that S1pr4 activation enhances TLR response of resident Mϕs to increase CCL2 production, which attracts further Mϕs. Thus, S1pr4 may be a target to reduce perpetuating inflammatory responses.
The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect diurnal cortisol patterns. Under baseline conditions, we collected morning and afternoon saliva samples of 10 animals (three zoos) on different days in two study periods (n = 3–10 per animal, daytime and period). Under stress conditions, we sampled the transported cow (newcomer) and the two cows of the destination zoo before and after the transport in the morning and afternoon (n = 3–9 per animal, daytime and transport phase), as well as after the first introduction of the newcomer to the bull (n = 1 per animal). Cortisol was measured in unextracted samples by enzyme immunoassay. Under baseline conditions, we observed the expected diurnal variation with higher cortisol levels in the morning than in the afternoon. Under stress conditions, neither a significant difference between pre‐ and posttransport, nor between morning and afternoon levels was found. The percentage difference between morning and afternoon cortisol after the transport, however, was remarkably lower than before the transport in the newcomer potentially indicating a stress response to familiarization. Saliva samples taken immediately after the introduction of the newcomer to the bull revealed a marked cortisol increase. Our findings indicate that stressors may disturb the diurnal cortisol rhythm. Furthermore, provided that samples can be collected promptly, salivary cortisol is a useful minimally invasive measure of physiological stress in the African elephant.
The opportunistic human pathogen Acinetobacter baumannii is one of the leading causes of nosocomial infections. The high prevalence of multidrug‐resistant strains, a high adaptability to changing environments and an overall pronounced stress resistance contribute to persistence and spread of the bacteria in hospitals and thereby promote repeated outbreaks. Altogether, the success of A. baumannii is mainly built on adaptation and stress resistance mechanisms, rather than relying on ‘true’ virulence factors. One of the stress factors that pathogens must cope with is osmolarity, which can differ between the external environment and different body parts of the human host. A. baumannii ATCC 19606T accumulates the compatible solutes glutamate, mannitol and trehalose in response to high salinities. In this work, it was found that most of the solutes vanish immediately after reaching stationary phase, a very unusual phenomenon. While glutamate can be metabolized, mannitol produced by MtlD is excreted to the medium in high amounts. First results indicate that A. baumannii ATCC 19606T undergoes a rapid switch to a dormant state (viable but non‐culturable) after disappearance of the compatible solutes. Resuscitation from this state could easily be achieved in PBS or fresh medium.
5‐Lipoxygenase (5‐LO) is the initial enzyme in the biosynthesis of leukotrienes, which are mediators involved in pathophysiological conditions such as asthma and certain cancer types. Knowledge of proteins involved in 5‐LO pathway regulation, including gene regulatory proteins, is needed to evaluate all options for therapeutic intervention in these diseases. Here, we present a mass spectrometric screening of ALOX5 promoter‐interacting proteins, obtained by DNA pulldown and label‐free quantitative mass spectrometry. Protein preparations from myeloid and B‐lymphocytic cell lines were screened for promoter DNA interactors. Through statistical analysis, 66 proteins were identified as specific ALOX5 promotor binding proteins. Among those, the 15 most likely candidates for a prominent role in ALOX5 gene regulation are the known ALOX5 interactors Sp1 and Sp3, the related factor Sp2, two Krüppel‐like factors (KLF13 and KLF16) and six other zinc finger proteins (MAZ, PRDM10, VEZF1, ZBTB7A, ZNF281 and ZNF579). Intriguingly, we also identified two helicases (BLM and DHX36) and the proteins hnRNPD and hnRNPK, which are, together with the protein MAZ, known to interact with DNA G‐quadruplex structures. As G‐quadruplexes are implicated in gene regulation, spectroscopic and antibody‐based methods were used to confirm their presence within the GC‐rich sequence of the ALOX5 promoter. In summary, we have systematically characterized the interactome of the ALOX5 promoter, identifying several zinc finger proteins as novel potential ALOX5 gene regulators. Further, we have shown that the ALOX5 promoter can form DNA G‐quadruplex structures, which may play a functional role in ALOX5 gene regulation.
Global‐scale gradient‐based groundwater models are a new endeavor for hydrologists who wish to improve global hydrological models (GHMs). In particular, the integration of such groundwater models into GHMs improves the simulation of water flows between surface water and groundwater and of capillary rise and thus evapotranspiration. Currently, these models are not able to simulate water table depth adequately over the entire globe. Unsatisfactory model performance compared to well observations suggests that a higher spatial resolution is required to better represent the high spatial variability of land surface and groundwater elevations. In this study, we use New Zealand as a testbed and analyze the impacts of spatial resolution on the results of global groundwater models. Steady‐state hydraulic heads simulated by two versions of the global groundwater model G3M, at spatial resolutions of 5 arc‐minutes (9 km) and 30 arc‐seconds (900 m), are compared with observations from the Canterbury region. The output of three other groundwater models with different spatial resolutions is analyzed as well. Considering the spatial distribution of residuals, general patterns of unsatisfactory model performance remain at the higher resolutions, suggesting that an increase in model resolution alone does not fix problems such as the systematic overestimation of hydraulic head. We conclude that (1) a new understanding of how low‐resolution global groundwater models can be evaluated is required, and (2) merely increasing the spatial resolution of global‐scale groundwater models will not improve the simulation of the global freshwater system.
Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
The ruling of the German Federal Constitutional Court and its call for conducting and communicating proportionality assessments regarding monetary policy have been the subject of some controversy. However, it can also be understood as a way to strengthen the de-facto independence of the European Central Bank. The authors shows how a regular proportionality check could be integrated in the ECB’s strategy that is currently undergoing a systematic review. In particular, they propose to include quantitative benchmarks for policy rates and the central bank balance sheet. Deviations from such benchmarks can have benefits in terms of the intended path for inflation while involving costs in terms of risks and side effects that need to be balanced. Practical applications to the euro area are provided
In this paper we adapt the Hamiltonian Monte Carlo (HMC) estimator to DSGE models, a method presently used in various fields due to its superior sampling and diagnostic properties. We implement it into a state-of-theart, freely available high-performance software package, STAN. We estimate a small scale textbook New-Keynesian model and the Smets-Wouters model using US data. Our results and sampling diagnostics confirm the parameter estimates available in existing literature. In addition, we find bimodality in the Smets-Wouters model even if we estimate the model using the original tight priors. Finally, we combine the HMC framework with the Sequential Monte Carlo (SMC) algorithm to create a powerful tool which permits the estimation of DSGE models with ill-behaved posterior densities.