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Intet resumé

Functional analysis of Ectodysplasin-A mutations causing selective tooth agenesis.

Mutations of the Ectodysplasin-A (EDA) gene are generally associated with the syndrome hypohidrotic ectodermal dysplasia (MIM 305100), but they can also manifest as selective, non-syndromic tooth agenesis (MIM300606). We have performed an in vitro functional analysis of six selective tooth agenesis-causing EDA mutations (one novel and five known) that are located in the C-terminal tumor necrosis factor homology domain of the protein. Our study reveals that expression, receptor binding or signaling capability of the mutant EDA1 proteins is only impaired in contrast to syndrome-causing mutations, which we have previously shown to abolish EDA1 expression, receptor binding or signaling. Our results support a model in which the development of the human dentition, especially of anterior teeth, requires the highest level of EDA-receptor signaling, whereas other ectodermal appendages, including posterior teeth, have less stringent requirements and form normally in response to EDA mutations with reduced activity

Defects and rescue of the minor salivary glands in Eda pathway mutants

AbstractDespite their importance to oral health, the mechanisms of minor salivary gland (SG) development are largely unexplored. Here we present in vivo and in vitro analyses of developing minor SGs in wild type and mutant mice. Eda, Shh and Fgf signalling pathway genes are expressed in these glands from an early stage of development. Developing minor SGs are absent in Eda pathway mutant embryos, and these mice exhibit a dysplastic circumvallate papilla with disrupted Shh expression. Supplementation of Eda pathway mutant minor SG explants with recombinant EDA rescues minor SG induction. Supplementation with Fgf8 or Shh, previously reported targets of Eda signalling, leads to induction of gland like structures in a few cases, but these fail to develop into minor SGs

Salivary gland branching morphogenesis: a quantitative systems analysis of the Eda/Edar/NFκB paradigm

<p>Abstract</p> <p>Background</p> <p>Ectodysplasin-A appears to be a critical component of branching morphogenesis. Mutations in mouse <it>Eda </it>or human <it>EDA </it>are associated with absent or hypoplastic sweat glands, sebaceous glands, lacrimal glands, salivary glands (SMGs), mammary glands and/or nipples, and mucous glands of the bronchial, esophageal and colonic mucosa. In this study, we utilized <it>Eda</it>^{<it>Ta </it>}(Tabby) mutant mice to investigate how a marked reduction in functional Eda propagates with time through a defined genetic subcircuit and to test the proposition that canonical NFκB signaling is sufficient to account for the differential expression of developmentally regulated genes in the context of <it>Eda </it>polymorphism.</p> <p>Results</p> <p>The quantitative systems analyses do not support the stated hypothesis. For most NFκB-regulated genes, the observed time course of gene expression is nearly unchanged in Tabby (<it>Eda</it>^<it>Ta</it>) as compared to wildtype mice, as is NFκB itself. Importantly, a subset of genes is dramatically differentially expressed in Tabby (<it>Edar</it>, <it>Fgf8</it>, <it>Shh</it>, <it>Egf</it>, <it>Tgfa</it>, <it>Egfr</it>), strongly suggesting the existence of an alternative Eda-mediated transcriptional pathway pivotal for SMG ontogeny. Experimental and <it>in silico </it>investigations have identified C/EBPα as a promising candidate.</p> <p>Conclusion</p> <p>In Tabby SMGs, upregulation of the Egf/Tgfα/Egfr pathway appears to mitigate the potentially severe abnormal phenotype predicted by the downregulation of Fgf8 and Shh. Others have suggested that the buffering of the phenotypic outcome that is coincident with variant Eda signaling could be a common mechanism that permits viable and diverse phenotypes, normal and abnormal. Our results support this proposition. Further, if branching epithelia use variations of a canonical developmental program, our results are likely applicable to understanding the phenotypes of other branching organs affected by <it>Eda </it>(<it>EDA</it>) mutation.</p

PM - en standhaftig frihedskæmper

I have known Poul Meyer (PM) from my childhood, but only recently have I tried to understand who he was and how his life influenced not only me, but many other people as well. Not many people know his life story – so through this article, I have tried to shed some light on certain periods of his life. He was born in Copenhagen in 1916 to a Jewish father and a non-Jewish mother. At a very young age, he converted to Judaism and saw himself as a spokesman for the Jewish Religion. His “career” in that field started with a lecture to his class in third grade. PM was awarded his Law degree (cand.jur.) from Copenhagen University in 1941, and he was employed by the Ministry of Agriculture – with an interruption in the years 1943-45 when he was in Sweden; in 1959 he was appointed Professor of Political Science at Aarhus University as one of the founding members of the Faculty. From his early youth, PM was politically active – first in the Conservative Youth Movement; during the occupation as co-founder and editor of the illegal magazine Hjemmefronten; and in the years 1945-1948 as a member of the “South Schleswig Committee of 5 May 1945”. After his death in 1990, some of his former pupils took the initiative to print three chapters from his large private archives. The book was named Nederlag (Defeat) and addresses three important periods in PM’s life. PM himself writes that these three chapters relate to the three important political campaigns in which he was involved; all three of which he lost. Unfortunately his archives perished, but through his son, Aksel, I have been able to review some manuscripts which have been the basis for my article, together with the book Nederlag. The idea to write this article came when I interviewed the youngest son of Bishop Hans Fuglsang-Damgaard about his father’s activities during the Second World War. During the interview he mentioned that from time to time, people were hidden in the Bishop’s house – freedom fighters, as well as Jews who had to flee to Sweden. In this context, he mentioned the name Poul Meyer, without knowing that PM had been part of my life. That was the moment when I said to myself that I want to tell the story of a man who was involved in the very nationalistic Conservative party, had been photographed together with Mussolini, and strongly believed that South Schleswig should again become a part of Denmark

Att vara subjekt eller objekt : Kroppsbild hos kvinnor och män

Det kulturella smalhetsidealet innebär negativa konsekvenser för individens psykologiska välbefinnande. Individen upplever en diskrepans mellan den ideala kroppsformen och hur de själva ser ut. Den sociala konstruktionen av den kvinnliga och manliga kroppen skapar olika villkor för kvinnor och män att förhålla sig till sin kropp som ett subjekt eller objekt. Syftet med föreliggande studie var att med hjälp av självskattningsskalor mäta upplevelse av objektifiering, body-esteem, restriktivt ätande och motionsvanor hos kvinnor (n= 61) och män (n= 53). Kvinnor upplever större objektifiering, har lägre body-esteem, äter oftare restriktivt samt motionerar oftare för att kontrollera vikten jämfört med män. Sambandet mellan objektifiering och body-esteem är negativt för kvinnor. Det tyder på att kvinnor är mer utsatta för objektifiering jämfört med män samt att objektifiering kan användas för att förstå kvinnors negativa body-estee