Ethnic minority organisations in Russia and Poland: a comparison challenge

This article proposes a framework for classifying ethnic minority organisations based on a broad combination of discursive and non-discursive criteria rooted in their political opportunities profile. One diasporic and one non-diasporic organisation were chosen for Russia and Poland, respectively. Diasporicity is understood according to William Safran’s criteria and Rogers Brubaker’s triadic configuration. The Russian study cases are Komi Voityr and the Russian Polish Congress; the Polish, the Silesian Autonomy Movement and the Belarussian House. The analysis of their status, activities, domestic and external political impact, localisation and role in the ‘triadic configuration’ has shown that the four cases are ethnic minority associations, and their legal status and scope of activities differ significantly. Their domestic political opportunities are rather scarce. Out of the four cases, just one organisation is an active part in Brubaker’s classical triadic configuration; its role is not traditional, ascribed to the respective ‘angle’. Although both Russian associations enjoy an official status, their activities are limited to the cultural, memorial and linguistic domains, primarily at the national level. In Poland, both associations act internationally as advocacy groups, and their activities are not confined to culture and language. Far from being universally applicable, the proposed classification framework can still add to the comparative ethnic politics toolkit

TRANSFORMATION OF COLONIAL EXPERIENCE REFLECTION IN THE BELGIAN PUBLIC DISCOURSE

In the article, the dynamics in the perception of the Belgian colonial experience in Congo are examined on the evidence of public discourse produced by public political actors in contemporary Belgium. Apart from the universally accepted postcolonial and decolonial optics, the authors suggest employing the five stages of grief model by Kübler-Ross, widespread in psychoanalysis. The concluding stage of acceptance took place in the 2020s caused mainly by public demand; it was performatively landmarked by the return of the Congolese prime minister's remains to his homeland. The authors demonstrate the complexity of the common historical experience reflection in the European and African states and the necessity of this reflection for the dynamic development of bilateral and multilateral ties

A syntenic cross species aneuploidy genetic screen links RCAN1 expression to β-cell mitochondrial dysfunction in type 2 diabetes

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucosestimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D. Author Summary Mitochondrial dysfunction and reduced insulin secretion are key features of β-cell dysfunction in Type 2 diabetes (T2D). Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21 that also displays β-cell mitochondrial dysfunction and reduced insulin secretion in humans. Given these similarities in β-cell dysfunction in T2D and DS, we developed a trisomy 21 screening method to identify genes that may be important in T2D. This approach used different DS mouse models combined with human gene expression data from T2D β-cells. From this we identified a single candidate, Regulator of calcineurin 1 (RCAN1). High RCAN1 expression occurs in human and mouse T2D islets. Increased RCAN1 expression in mice reduced β-cell mitochondrial function and ATP availability, and this has negative implications for multiple ATP-dependent steps in glucose- stimulated insulin secretion

RCAN1 expression and methylation in human and mouse Type 2 diabetic islets.

<p>(A) RCAN1 gene expression in human non-diabetic (ND, n = 77, blue symbols) and type 2 diabetic islets (T2D, n = 12, red symbols). (B) RCAN1 expression vs donor HbA1c (n = 89). RCAN1 expression and methylation status at sites (C) cg05056497, (D) cg05156137 and (E) cg21301258 are strongly correlated. (F) RCAN1.1 and RCAN1.4 protein expression in human islets. (G) Quantification of RCAN1 islet protein expression in human islets (n = 3), mouse islets (n = 5) and mouse MIN6 β-cells (n = 3). (H) RCAN1.1 and RCAN1.4 protein expression in control (db/+) and db/db islets. (I) Quantification of (G) (n = 6 control, n = 5 db/db). **<i>p</i> < 0.01, ***<i>p</i> < 0.001.</p

A DS screening approach identifies a region of chromosome 21 associated with hyperglycemia.

<p>(A) Fasting blood glucose in Ts65Dn (n = 14), Dp16 (n = 11), Ts1Rhr (n = 12) and Tc1 (n = 23) mice (filled symbols) and their respective controls (open symbols). (B) Glucose tolerance test in Ts65Dn (n = 5) and control (n = 6) mice and (C) area under the curve analysis. (D) Glucose tolerance test in Tc1 (n = 9) and control (n = 8) mice and (E) area under the curve analysis. (F) Illustration of the trisomic regions in these DS models used and the 5 genes associated with hyperglycemia in DS that are up-regulated in human T2D islets. *<i>p</i> < 0.05, **<i>p</i> < 0.01.</p

GSIS is reduced <i>in vivo</i> in RCAN1^ox β-cells.

<p>(A) Plasma insulin is similar in WT and RCAN1^ox mice (n = 3). (B) <i>in vivo</i> GSIS is lower in RCAN1^ox mice as defined by (C) reduced area under the curve (AUC) for insulin secretion over 1 hour (n = 3). (D) Insulin sensitivity in WT (n = 4) and RCAN1^ox (n = 5) mice is not different as defined by (E) AUC analysis. (F) Plasma glucagon levels are similar in WT (n = 5) and RCAN1^ox (n = 4) mice. Data represents the mean ± SEM, *p<0.05.</p

Glucose-dependent membrane depolarisation is reduced in RCAN1^ox β-cells.

<p>Voltage clamp recordings in (A) WT and (B) RCAN1^ox β-cells. Scale bar in A is 20ms and 20pA in A and B. (C) Current-voltage relationship in WT (n = 59) and RCAN1^ox (n = 39) β-cells. Current clamp recordings from (D) WT and (E) RCAN1^ox β-cells in response to 20mM glucose (arrow). (F) Membrane potential change in response to 20mM glucose in WT (n = 6) and RCAN1^ox (n = 7) β-cells (**<i>p</i> < 0.01). Current clamp recordings from (G) WT and (H) RCAN1^ox β-cells in response to tolbutamide (100μM, arrow). (I) Membrane potential change in response to tolbutamide in WT (n = 6) and RCAN1^ox (n = 6) β-cells.</p

RCAN1 effects mitochondrial membrane potential, not volume.

<p>(A) Representative western blots of wild type (WT) and RCAN1^ox islet protein lysates probed against NDUFA9, SDHA, CORE1, Opa1 and TOM20. Electron microscopy analysis of (B) total mitochondrial area and (C) relative area in WT (n = 8 β-cells) and RCAN1^ox (n = 6 β-cells). (D) TMRM staining in live cells further demonstrates a lack of difference in mitochondrial volume between WT (n = 43 cells) and RCAN1^ox (n = 46 cells). (E) Mitochondrial membrane potential measured as mean cell TMRM fluorescence in low and high glucose in WT and RCAN1^ox cells (n = 17–21 cell/group). Data represents the mean ±SEM, *p<0.05.</p

Mitochondrial respiratory output is reduced in RCAN1^ox islets.

<p>(A) Oxygen consumption rate (OCR) in WT (n = 5) and RCAN1^ox (n = 6) islets under various conditions. (B) OCR in 3 mM or 20 mM glucose. (C) Islet ATP levels (n = 7 WT and n = 4 RCAN1^ox). (D) Methyl-succinate-induced (10 mM) insulin secretion (n = 4/group). (E) Effect of carboxyatractyloside (CATS, 200 μm) on insulin secretion in response to 20 mM glucose (n = 4–7). Immunocytochemical labelling of (F) RCAN1, (G) mitochondria (Mitotracker Red) and (H) both in MIN6 cells. *<i>p</i> < 0.05, **<i>p</i> < 0.01.</p