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Over the last decades, many democracies progressed in the political inclusion of Indigenous people and the recognition of their rights. Does this contribute to how satisfied Indigenous people are with how democracy works? Prior empirical evidence suggests it does. As yet, there is, however, little study of the underlying mechanisms and we should not assume a categorically positive correlation between political equality and satisfaction with democracy. Instead, Indigenous affairs need to be sufficiently politicized to matter for Indigenous people's satisfaction with democracy. I test this argument in the case of the Sámi people in Norway and Sweden. While political inequality is comparatively higher in Sweden, Sámi issues are less politicized. Using novel original survey data, I find that here, satisfaction with democracy is not correlated with Sámi ethnicity. Satisfaction levels among Norwegian Sámi, though, are significantly lower than among their non-Indigenous compatriots and strongly shaped by considerations of political inequality. [ABSTRACT FROM AUTHOR]

The Sámi people stand out as the only Indigenous minority in an egalitarian European context, namely the Nordic Countries. Therefore, inequalities that they may face are worth closer inspection. Drawing on the distinction between inequalities among individuals (vertical) and between groups (horizontal), we investigate how different types of inequalities affect the Sámi today. We formulate a series of hypotheses on how social, economic, cultural, and political inequalities are linked with discrimination experience, and test these with original data from a population survey conducted in northern Norway and northern Sweden simultaneously in 2021. The findings show that Sámi ethnic background increases the probability of experiencing discrimination. While individual-level economic inequality is also pertinent, this does not directly materialise as between-group inequality. Instead, minority language use is a strong predictor of discrimination experience, revealing the socio-cultural nature of ethnic inequalities. Cross-country differences are only reflected in the effect of minority language use. [ABSTRACT FROM AUTHOR]

Background: Cell-type heterogeneity of tumors is a key factor in tumor progression and response to chemotherapy. Tumor cell-type heterogeneity, defined as the proportion of the various cell-types in a tumor, can be inferred from DNA methylation of surgical specimens. However, confounding factors known to associate with methylation values, such as age and sex, complicate accurate inference of cell-type proportions. While reference-free algorithms have been developed to infer cell-type proportions from DNA methylation, a comparative evaluation of the performance of these methods is still lacking. Results: Here we use simulations to evaluate several computational pipelines based on the software packages MeDeCom, EDec, and RefFreeEWAS. We identify that accounting for confounders, feature selection, and the choice of the number of estimated cell types are critical steps for inferring cell-type proportions. We find that removal of methylation probes which are correlated with confounder variables reduces the error of inference by 30–35%, and that selection of cell-type informative probes has similar effect. We show that Cattell's rule based on the scree plot is a powerful tool to determine the number of cell-types. Once the pre-processing steps are achieved, the three deconvolution methods provide comparable results. We observe that all the algorithms' performance improves when inter-sample variation of cell-type proportions is large or when the number of available samples is large. We find that under specific circumstances the methods are sensitive to the initialization method, suggesting that averaging different solutions or optimizing initialization is an avenue for future research. Conclusion: Based on the lessons learned, to facilitate pipeline validation and catalyze further pipeline improvement by the community, we develop a benchmark pipeline for inference of cell-type proportions and implement it in the R package medepir. [ABSTRACT FROM AUTHOR]

We studied transgenic mice with cardiac-specific overexpression of H 2 -histamine receptors (H 2 -TG) by using the α -myosin heavy-chain promoter. We wanted to address whether this overexpression would protect the heart against paradigmatic stressors. To this end, we studied isolated atrial preparations in an organ bath under normoxic and hypoxic conditions and after prolonged exposure to high histamine concentrations. Moreover, we assessed cardiac function using echocardiography in mice with cardiac hypertrophy due to overexpression of the catalytic subunit of PP2A (PP2A-TG) in the heart [H 2 -TG × PP2A-TG = double transgenic (DT)] or H 2 -TG with cardiac systolic failure due to treatment of mice with lipopolysaccharides (LPSs). Furthermore, the effect of ischemia and reperfusion was studied in isolated perfused hearts (Langendorff mode) of H 2 -TG. We detected evidence for the protective role of the overexpressed H 2 -histamine receptors in the contractile dysfunction of DT and isolated atrial preparations subjected to hypoxia. In contrast, we noted the detrimental role of H 2 -histamine receptor overexpression against ischemia (Langendorff perfusion) and LPS-induced systolic heart failure. Hence, the role of H 2 -histamine receptors in the heart is context-sensitive: the results differ between hypoxia (in atrium) and ischemia (perfused whole heart), as well as between genetically induced hypertrophy (DT) and toxin-induced heart failure (LPS). The underlying molecular mechanisms for the protective or detrimental roles of H 2 -histamine receptor overexpression in the mammalian heart remain to be elucidated. SIGNIFICANCE STATEMENT: The beneficial and detrimental effects of the cardiac effects of H 2 -histamine receptors in the heart under stressful conditions, here intended to mimic clinical situations, were studied. The data suggest that depending on the clinically underlying cardiac pathophysiological mechanisms, H 2 -histamine agonists or H 2 -histamine antagonists might merit further research efforts to improve clinical drug therapy., (Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.)