The Embodiment of Tolerance in Discourses and Practices addressing Cultural and Religious Diversity in the Political Sphere in Ireland

Work Package 4: National Case Studies of Challenges to Tolerance in Political LifeThe ACCEPT PLURALISM project (2010-2013) is funded by the European Commission under the Seventh Framework Programme, Socio-economic Sciences and Humanities. (Call FP7-SSH-2009-A, Grant Agreement no: 243837). Coordinator: Prof. Anna Triandafyllidou, Robert Schuman Centre for Advanced Studies, European University Institute

The Embodiment of Tolerance in Discourses and Practices Addressing Cultural Diversity in Irish schools

Work Package 3: National Case Studies of Challenges to Tolerance in School LifeThe ACCEPT PLURALISM project (2010-2013) is funded by the European Commission under the Seventh Framework Programme, Socio-economic Sciences and Humanities. (Call FP7-SSH-2009-A, Grant Agreement no: 243837). Coordinator: Prof. Anna Triandafyllidou, Robert Schuman Centre for Advanced Studies, European University Institute

Invest Ophthalmol Vis Sci

PURPOSE. Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients' genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France.METHODS. A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed.RESULTS. In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A twoby-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87).CONCLUSIONS. We described a genotype-phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA

5-Methylcytosine and 5-Hydroxymethylcytosine Spatiotemporal Profiles in the Mouse Zygote

Background: In the mouse zygote, DNA methylation patterns are heavily modified, and differ between the maternal and paternal pronucleus. Demethylation of the paternal genome has been described as an active and replication-independent process, although the mechanisms responsible for it remain elusive. Recently, 5-hydroxymethylcytosine has been suggested as an intermediate in this demethylation. Methodology/principal findings: In this study, we quantified DNA methylation and hydroxymethylation in both pronuclei of the mouse zygote during the replication period and we examined their patterns on the pericentric heterochromatin using 3D immuno-FISH. Our results demonstrate that 5-methylcytosine and 5-hydroxymethylcytosine localizations on the pericentric sequences are not complementary; indeed we observe no enrichment of either marks on some regions and an enrichment of both on others. In addition, we show that DNA demethylation continues during DNA replication, and is inhibited by aphidicolin. Finally, we observe notable differences in the kinetics of demethylation and hydroxymethylation; in particular, a peak of 5-hydroxymethylcytosine, unrelated to any change in 5-methylcytosine level, is observed after completion of replication. Conclusion/significance: Together our results support the already proposed hypothesis that 5-hydroxymethylcytosine is not a simple intermediate in an active demethylation process and could play a role of its own during early development

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Merkel Cells as Putative Regulatory Cells in Skin Disorders: An In Vitro Study

Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca2+-independent, as inhibition of Ca2+ channels or culture in the absence of Ca2+ failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated

Challenges of Immigrant Religious Diversity in Irish Schools

Work Package 3: National Case Studies of Challenges to Tolerance in School LifeThe ACCEPT PLURALISM project (2010-2013) is funded by the European Commission under the Seventh Framework Programme, Socio-economic Sciences and Humanities. (Call FP7-SSH-2009-A, Grant Agreement no: 243837). Coordinator: Prof. Anna Triandafyllidou, Robert Schuman Centre for Advanced Studies, European University Institute

New knowledge about Ireland

Work Package 5: New Knowledge on Tolerance and Cultural Diversity in EuropeIreland, an emigration state par excellence, was the last country in Western Europe to become an important destination for migrants. In the period from the mid-1980s to the early 2000s, Ireland transformed itself from one of the poorest EU countries with high levels of unemployment and emigration to a centre for high-tech industry and impressive growth rates. In the 1990s the country began receiving a significant number of immigrants for the first time in its history, and by 1996 immigration exceeded emigration. By the time of the 2011 Census, non-Irish nationals represented 12% (or 544,360) of the population and included 196 different nationalities.The ACCEPT PLURALISM project (2010-2013) is funded by the European Commission under the Seventh Framework Programme, Socio-economic Sciences and Humanities. (Call FP7-SSH-2009-A, Grant Agreement no: 243837). Coordinator: Prof. Anna Triandafyllidou, Robert Schuman Centre for Advanced Studies, European University Institute

Tolerance and Cultural Diversity Discourses in Ireland

Work Package 1: Overview of National Discourses on Tolerance and Cultural diversity (Literature and Realities)The ACCEPT PLURALISM project (2010-2013) is funded by the European Commission under the Seventh Framework Programme, Socio-economic Sciences and Humanities. (Call FP7-SSH-2009-A, Grant Agreement no: 243837). Coordinator: Prof. Anna Triandafyllidou, Robert Schuman Centre for Advanced Studies, European University Institute

Tolerance and Cultural Diversity in Ireland, Concepts and Practices

Work Package 5: New Knowledge on Tolerance and Cultural Diversity in EuropeThe ACCEPT PLURALISM project (2010-2013) is funded by the European Commission under the Seventh Framework Programme, Socio-economic Sciences and Humanities. (Call FP7-SSH-2009-A, Grant Agreement no: 243837). Coordinator: Prof. Anna Triandafyllidou, Robert Schuman Centre for Advanced Studies, European University Institute