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Accepted manuscript version to be published in https://www.nature.com/palcomms/. In this paper, we examine ethnic discrimination using sport as a laboratory. Applying a field experiment in the three Scandinavian countries – Sweden, Norway, and Denmark – we test whether foreign female minority groups experience greater rejection rates when seeking inclusion in amateur soccer clubs. Soccer coaches were contacted by e-mail using native and foreign-sounding names from selected groups, requesting to participate in trial practice. Previous findings show persistent discrimination of foreign minority groups in the labour market, and recent work suggests that discrimination also occurs in the context of soccer. Our findings from Scandinavia show that Sweden is the only country that shows statistically significant signs of discriminatory patterns, and the probability of experiencing discrimination increases with cultural distance. However, cultural distance appears to have no influence in Norway and Denmark. We further investigate whether male or female coaches demonstrate different discriminatory behaviour when being contacted, but our analysis shows almost no gender differences. Findings suggest that how men and women differ in their discriminatory behaviour is context specific. The differences identified across nations and previous studies are discussed to better understand the mechanisms of discrimination.

The neurotransmitter:sodium symporters (NSSs) are secondary active transporters that couple the reuptake of substrate to the symport of one or two sodium ions. One bound Na+(Na1) contributes to the substrate binding, while the other Na+(Na2) is thought to be involved in the conformational transition of the NSS. Two NSS members, the serotonin transporter (SERT) and theDrosophiladopamine transporter (dDAT), also couple substrate uptake to the antiport of K+by a largely undefined mechanism. We have previously shown that the bacterial NSS homologue, LeuT, also binds K+, and could therefore serve as a model protein for the exploration of K+binding in NSS proteins. Here, we characterize the impact of K+on substrate affinity and transport as well as on LeuT conformational equilibrium states. Both radioligand binding assays and transition metal ion FRET (tmFRET) yielded similar K+affinities for LeuT. K+binding was specific and saturable. LeuT reconstituted into proteoliposomes showed that intra-vesicular K+dose-dependently increased the transport velocity of [3H]alanine, whereas extra-vesicular K+had no apparent effect. K+-binding induced a LeuT conformation distinct from the Na+- and substrate-bound conformation. Conservative mutations of the Na1 site residues affected the binding of Na+and K+to different degrees. The Na1 site mutation N27Q caused a >10-fold decrease in K+affinity but at the same time a ~3-fold increase in Na+affinity. Together, the results suggest that K+-binding to LeuT modulates substrate transport and that the K+affinity and selectivity for LeuT is sensitive to mutations in the Na1 site, pointing toward the Na1 site as a candidate site for facilitating the interaction between K+in some NNSs.

A large number of studies, all using Bayesian parameter inference from Markov chain Monte Carlo methods, have constrained the presence of a decaying dark matter component. All such studies find a strong preference for either very long-lived or very short-lived dark matter. However, in this paper, we demonstrate that this preference is due to parameter volume effects that drive the model towards the standard ΛCDM model, which is known to provide a good fit to most observational data. Using profile likelihoods, which are free from volume effects, we instead find that the best-fitting parameters are associated with an intermediate regime where around 3% of cold dark matter decays just prior to recombination. With two additional parameters, the model yields an overall preference over the ΛCDM model of Δχ2≈-2.8 with Planck and BAO and Δχ2≈-7.8 with the SH0ES H0 measurement, while only slightly alleviating the H0 tension. Ultimately, our results reveal that decaying dark matter is more viable than previously assumed, and illustrate the dangers of relying exclusively on Bayesian parameter inference when analyzsing extensions to the ΛCDM model.

Background and purpose Activation of hepatic thyroid hormone receptor β (THR-β) is associated with systemic lipid lowering, increased bile acid synthesis, and fat oxidation. In patients with non-alcoholic steatohepatitis (NASH), treatment with THR-β agonists decreased hepatic steatosis and circulating lipids, and induced resolution of NASH. We chose resmetirom (MGL-3196), a liver-directed, selective THR-β agonist, as a prototype to investigate the effects of THR-β activation in mice with diet-induced obesity (DIO) and biopsy-confirmed advanced NASH with fibrosis. Experimental approach C57Bl/6J mice were fed a diet high in fat, fructose, and cholesterol for 34 weeks, and only biopsy-confirmed DIO-NASH mice with fibrosis were included. Resmetirom was administered at a daily dose of 3 mg·kg-1 p.o., for 8 weeks. Systemic and hepatic metabolic parameters, histological non-alcoholic fatty liver disease (NAFLD) activity and fibrosis scores, and liver RNA expression profiles were determined to assess the effect of THR-β activation. Key results Treatment with resmetirom did not influence body weight but led to significant reduction in liver weight, hepatic steatosis, plasma alanine aminotransferase activity, liver and plasma cholesterol, and blood glucose. These metabolic effects translated into significant improvement in NAFLD activity score. Moreover, a lower content of α-smooth muscle actin and down-regulation of genes involved in fibrogenesis indicated a decrease in hepatic fibrosis. Conclusion and implications Our model robustly reflected clinical observations of body weight-independent improvements in systemic and hepatic metabolism including anti-steatotic activity.

Membrane protein structures provide atomic level insight into essential biochemical processes and facilitate protein structure-based drug design. However, the inherent instability of these bio-macromolecules outside lipid bilayers hampers their structural and functional study. Detergent micelles can be used to solubilize and stabilize these membrane-inserted proteins in aqueous solution, thereby enabling their downstream characterizations. Membrane proteins encapsulated in detergent micelles tend to denature and aggregate over time, highlighting the need for development of new amphiphiles effective for protein solubility and stability. In this work, we present newly-designed maltoside detergents containing a pendant chain attached to a glycerol-decorated tris(hydroxymethyl)methane (THM) core, designated GTMs. One set of the GTMs has a hydrophobic pendant (ethyl chain; E-GTMs), and the other set has a hydrophilic pendant (methoxyethoxylmethyl chain; M-GTMs) placed in the hydrophobic-hydrophilic interfaces. The two sets of GTMs displayed profoundly different behaviors in terms of detergent self-assembly and protein stabilization efficacy. These behaviors mainly arise from the polarity difference between two pendants (ethyl and methoxyethoxylmethyl chains) that results in a large variation in detergent conformation between these sets of GTMs in aqueous media. The resulting high hydrophobic density in the detergent micelle interior is likely responsible for enhanced efficacy of the M-GTMs for protein stabilization compared to the E-GTMs and a gold standard detergent DDM. A representative GTM, M-GTM-O12, was more effective for protein stability than some recently developed detergents including LMNG. This is the first case study investigating the effect of pendant polarity on detergent geometry correlated with detergent efficacy for protein stabilization. Statement of significance This study introduces new amphiphiles for use as biochemical tools in membrane protein studies. We identified a few hydrophilic pendant-bearing amphiphiles such as M-GTM-O11 and M-GTM-O12 that & nbsp;show remarkable efficacy for membrane protein solubilization and stabilization compared to a gold stan-dard DDM, the hydrophobic counterparts (E-GTMs) and a significantly optimized detergent LMNG. In ad-dition, detergent results obtained in the current study reveals the effect of detergent pendant polarity on protein solubility and stability. Thus, the current study represents both significant chemical and con-ceptual advance. The detergent tools and design principle introduced here advance protein science and facilitate structure-based drug design and development. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

In this paper we update the constraints on the simple decaying cold dark matter (DCDM) model with dark radiation (DR) as decay product. We consider two different regimes of the lifetime, i.e. short-lived and long-lived, and use the most recent CMB data from Planck (2018) to infer new constraints on the decay parameters with which we compare the constraints inferred by the previous Planck data (2015). We hereby show that the newest CMB data constrains the fractional amount of DCDM twice as much as the previous data in the long-lived regime, leading to our current best 2$\sigma$ upper bound of $f_{\rm dcdm}, Comment: 22 pages, 9 figures. Major revision after submission to JCAP. Erroneous results have been corrected and a section discussing the impact on the Hubble and $\sigma_8$ tensions has been added

Aims To test specific mono‐agonists to the glucagon‐like peptide‐1 receptor (GLP‐1R), glucagon receptor (GCGR) and glucose‐dependent insulinotropic peptide receptor (GIPR), individually and in combination, in a mouse model of diet‐induced non‐alcoholic steatohepatitis (NASH) and fibrosis in order to decipher the contribution of their activities and potential additive effects to improving systemic and hepatic metabolism. Materials and methods We induced NASH by pre‐feeding C57BL/6J mice a diet rich in fat, fructose and cholesterol for 36 weeks. This was followed by 8 weeks of treatment with the receptor‐specific agonists 1‐GCG (20 mg/kg twice daily), 2‐GLP1 (3 mg/kg twice daily) or 3‐GIP (30 mg/kg twice daily), or the dual (1 + 2) or triple (1 + 2 + 3) combinations thereof. A dual GLP‐1R/GCGR agonistic peptide, 4‐dual‐GLP1/GCGR (30 mg/kg twice daily), and liraglutide (100 mg/kg twice daily) were included as references. Results Whereas low‐dose 1‐GCG or 3‐GIP alone did not influence body weight, liver lipids and histology, their combination with 2‐GLP1 provided additional weight loss, reduction in liver triglycerides and improvement in histological disease activity score. Notably, 4‐dual‐GLP‐1R/GCGR and the triple combination of selective mono‐agonists led to a significantly stronger reduction in the histological non‐alcoholic fatty liver disease activity score compared to high‐dose liraglutide, at the same extent of body weight loss. Conclusions GCGR and GIPR agonism provide additional, body weight‐independent improvements on top of GLP‐1R agonism in a murine model of manifest NASH with fibrosis.

It is a policy objective to increase the percentage of journeys made by bicycle in Norway from the current 5 % to 10 %. Kristiansand is one of the most active cities in Norway in terms of cycling. We wished to identify the extent of injuries among cyclists admitted to the hospital.We reviewed the medical records of patients with cycling-related injuries who were admitted to Sørlandet Hospital, Kristiansand in the period 1 January 2012 to 31 December 2015. Patient, accident, injury and treatment characteristics were recorded, as well as any sequelae after 12 months.Altogether 224 adults and 53 children (16 years) were registered with cycling-related injuries, most of which (n=192, 69 %) were mild/moderate. Very severe and critical injuries were recorded in 6 (11 %) children and 22 (10 %) adults. Fractures (n=179, 65 %) and minor head injuries (n= 78, 28 %) dominated the injury panorama. Surgical treatment was undertaken in 107 (48 %) adults and 19 (36 %) children. A total of 12 (4 %) patients were transferred to the trauma centre at Oslo University Hospital Ullevål. Four adults had significant sequelae after 12 months, all related to severe head/neck injury.A considerable proportion of serious and complex injuries require that the national guidelines for use of a trauma team be followed. Systematic and ongoing registration of cyclists' injuries in the form of a national registry could help increase our insight into the circumstances surrounding accidents and the extent of injuries related to these.

BACKGROUND It is a policy objective to increase the percentage of journeys made by bicycle in Norway from the current 5 % to 10 %. Kristiansand is one of the most active cities in Norway in terms of cycling. We wished to identify the extent of injuries among cyclists admitted to the hospital. MATERIAL AND METHOD We reviewed the medical records of patients with cycling-related injuries who were admitted to Sorlandet Hospital, Kristiansand in the period 1 January 2012 to 31 December 2015. Patient, accident, injury and treatment characteristics were recorded, as well as any sequelae after 12 months. RESULTS Altogether 224 adults and 53 children (

Denne oppgaven tar for seg konkurranseutsetting av offentlige tjenester, og om konkurranseutsetting kan være med på å forenkle styringen av tjenestene. Med forenkling mener vi bedring av de forhold som berører styringen av produksjonsenhetene. De forhold vi har tatt for oss er lovmessige, strukturelle og administrative forhold. Vi har gjennomført et casestudie innad i sykehjemstjenesten. Her har vi valgt ut et privat og et offentlig styrt sykehjem i Oslo kommune, og sett på styringsforholdet mellom sykehjemmene og deres motpart i Sykehjemsetaten. Ettersom store deler av sykehjemstjenesten i Norge ikke er konkurranseutsatt, har vi valgt å ta med en kontrollgruppe. Kommune A og Sykehjem A er med for å vise hvordan styringsforholdet i Oslo kan avvike fra hvordan resten av landet opererer. Med bakgrunn i dette har vi laget tre hypoteser med hensyn på styringsforholdet mellom sykehjem og kommune. Vi har intervjuet seks personer, fra de valgte sykehjem og kommuner, analysert svarene vi fikk og testet disse svarene opp mot hypotesene vi lagde. Til slutt har vi konkludert om vifant støtte for hypotesene eller ikke.