Lysyl hydroxylase 3 localizes to epidermal basement membrane and Is reduced in patients with Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention

I stadens skugga : den medeltida landsbygden som arkeologiskt forskningsfält

In this thesis focus is on two aims: 1) to investigate the emergence and establishment of medieval rural archaeology as an archaeological field of study, from the 1930’s up until today and 2) based on the results made in this study, to discuss generally how new subject areas are incorporated and maintained within the humanities. Thus, the scope of the thesis does not lie on the medieval period with its rural settlements and their inhabitants, but rather on their archaeological historiography during the 20th and 21st centuries. Sweden (Fosie) serves as a point of departure and together with examples from Germany (Hohenrode), Denmark (Store Valby) and Great Britain (Wharram Percy) the over decades changing practices and approaches are discussed and analyzed. Three conditions namely the technical, disciplinary and ideological constitute the theoretical foundations for the present study. In short, the technical conditions primarily relate to the fieldwork and the process of excavation at different times. The disciplinary conditions are defined as the study of those variables within the scientific sphere, and their internal relationship that have contributed to the formation of the field of medieval rural archaeology and its continued existence. In order to study these aspects the concept of boundary work has served as an inspiration. The ideological conditions focus on the interaction between archaeology and society, in my study mainly represented by discussions on the status of the medieval village in legislation. Based on theoretical discussions and analyses made in the empirical studies, it is argued that the emergence, establishment and upcoming changes of medieval rural archaeology as a field of study are best distinguished by identifying different promoting and constraining factors. These conclusions are followed by discussing how best characterize and describe different subject areas. Based on observations made, the metaphor of a web consisting out of different spatial and temporal levels and nodes is proposed. This model serves as a complement to a more traditional chronological scheme and, thus, it contributes to a more complete and deeper understanding of the structure of scientific fields. The argument is also that the models application is versatile to other disciplines

National Museums in Germany : Anchoring Competing Communities

From 1760-2010, Germany has been marked by several levels of nation-building as well as many different ideological and territorial projects. This inquiry has focused on processes of long continuity, spanning unification in both the nineteenth and twentieth centuries, adding the most important ruptures and institutional inventions to get a firm-enough basis for conclusions on the institutional role of museums vis-a-vis the state-making process. The most significant periods for the interaction between museums and nation-building can be labelled The struggle, leading to Germany’s unification in 1871, where several regions made their bids through museums. Imperial unity on display from 1871-1914. National museums were stabilizing and universalizing the German Empire in the world. Nazi cultural policy, 1933-1945: Comprehensive museum plans for the Third Reich. GDR (German Democratic Republic) national museums between 1949-1990 were dominated by the ideology of socialist culture. The Federal republic, before and after 1990: inscribing Nazi and GDR as pasts contained within brackets. Germany’s history is marked by the processes of unification meeting dissociative forces resulting in dramatic political shifts and the persistence of a complex federal structure. Museums reflect various strategies both within this history and through contributions to stabilizing, reinforcing and materializing ideas of continuity. Balancing the unifying message of the heritage of a Roman – German legacy and later federal structures resulted in a distribution of national museums in Berlin, Munich, Nuremberg and Bonn. A long-standing cooperation and tension between local, regional and national identities with a clear utopian and activist element marks initiatives taken for establishing national museums. What later became national museums often started as private individual or collective elite initiatives aimed at putting certain projects on the political agenda. The enlightenment ambitions went beyond national borders with the establishment of Humboldt University in Berlin in 1810 and several of the institutions at the Museumsinselas “Universalmuseen”. The scientific and technical scope of Deutsches Museum in Munich captured the rational dimension in German identity politics into the next century. These rational and scientific ambitions coincided in time and helped to legitimize both military national unification and imperial undertakings. Implicit and explicit historical narratives representing the existence of German culture dominated national museums with a plastic delimitation between a European (Roman), Germanspeaking and German state as the space of representation. Art and cultural history was more expandable, while political history followed the honours and sorrows of political community. National museums have, overall, survived with an astonishing continuity when successively changing the goal of state-making from creating the state, an empire, a Nazi state to overcoming that past and creating democratic visions in both liberal and communist versions to, again, healing that division and constructing it as a parenthesis in history. A re-nationalisation process post-1990 again activated investments in museums and reveals again a standing ambiguity in dealing with national sentiments. This is most clearly visible in museum discussions and projects dealing with the NS-legacy versus demands for “Normalisierung”. As opposed to many European countries from France to Greece that have a high level of centralization within the field of culture, both culture and cultural politics is, in Germany, mainly dealt with on a regional level within each Bundesland. This can partly be explained by the terrifying experience of a centralized rule and the misuse of art and culture for political ends made during the NS-regime (Klein 2003):71). After the war, one sought to prevent this through legislation by reducing state influence within the cultural policy sphere through the foundational law (GG article 5(3) and 30). A federal - and thus fragmented - Germany was also something desired by the Allies. However, a decentralized Germany was nothing entirely new. An on-going interplay between regional and central forces in representing the state was one of the long-term phenomena, although driven by various logics: In the mid-19th century, the relative strength and actual outcome of the unification process was naturally open-ended which allowed for several strong suggestions, while mid-20thcentury dynamics was determined by the urge not to repeat the mishaps of a strong national ideology. The current trend seems to lend itself to stronger nationalizing forces in the field of memory politics. The overarching argument of the role played by national museums in the making of the German state and nation is that it has provided a platform for a cultural constitution only slowly negotiating changing ideas of what it means to be German and how to relate to local, regional and transnational communities. Hence, the main impact of the museums is to secure ideas of continuity in the midst of dramatic political change.EuNaMu

National museums in Germany : anchoring competing communities

From 1760-2010, Germany has been marked by several levels of nation-building as well as many different ideological and territorial projects. This inquiry has focused on processes of long continuity, spanning unification in both the nineteenth and twentieth centuries, adding the most important ruptures and institutional inventions to get a firm-enough basis for conclusions on the institutional role of museums vis-a-vis the state-making process. The most significant periods for the interaction between museums and nation-building can be labelled The struggle, leading to Germany’s unification in 1871, where several regions made their bids through museums. Imperial unity on display from 1871-1914. National museums were stabilizing and universalizing the German Empire in the world. Nazi cultural policy, 1933-1945: Comprehensive museum plans for the Third Reich. GDR (German Democratic Republic) national museums between 1949-1990 were dominated by the ideology of socialist culture. The Federal republic, before and after 1990: inscribing Nazi and GDR as pasts contained within brackets. Germany’s history is marked by the processes of unification meeting dissociative forces resulting in dramatic political shifts and the persistence of a complex federal structure. Museums reflect various strategies both within this history and through contributions to stabilizing, reinforcing and materializing ideas of continuity. Balancing the unifying message of the heritage of a Roman – German legacy and later federal structures resulted in a distribution of national museums in Berlin, Munich, Nuremberg and Bonn. A long-standing cooperation and tension between local, regional and national identities with a clear utopian and activist element marks initiatives taken for establishing national museums. What later became national museums often started as private individual or collective elite initiatives aimed at putting certain projects on the political agenda. The enlightenment ambitions went beyond national borders with the establishment of Humboldt University in Berlin in 1810 and several of the institutions at the Museumsinselas “Universalmuseen”. The scientific and technical scope of Deutsches Museum in Munich captured the rational dimension in German identity politics into the next century. These rational and scientific ambitions coincided in time and helped to legitimize both military national unification and imperial undertakings. Implicit and explicit historical narratives representing the existence of German culture dominated national museums with a plastic delimitation between a European (Roman), Germanspeaking and German state as the space of representation. Art and cultural history was more expandable, while political history followed the honours and sorrows of political community. National museums have, overall, survived with an astonishing continuity when successively changing the goal of state-making from creating the state, an empire, a Nazi state to overcoming that past and creating democratic visions in both liberal and communist versions to, again, healing that division and constructing it as a parenthesis in history. A re-nationalisation process post-1990 again activated investments in museums and reveals again a standing ambiguity in dealing with national sentiments. This is most clearly visible in museum discussions and projects dealing with the NS-legacy versus demands for “Normalisierung”. As opposed to many European countries from France to Greece that have a high level of centralization within the field of culture, both culture and cultural politics is, in Germany, mainly dealt with on a regional level within each Bundesland. This can partly be explained by the terrifying experience of a centralized rule and the misuse of art and culture for political ends made during the NS-regime (Klein 2003):71). After the war, one sought to prevent this through legislation by reducing state influence within the cultural policy sphere through the foundational law (GG article 5(3) and 30). A federal - and thus fragmented - Germany was also something desired by the Allies. However, a decentralized Germany was nothing entirely new. An on-going interplay between regional and central forces in representing the state was one of the long-term phenomena, although driven by various logics: In the mid-19th century, the relative strength and actual outcome of the unification process was naturally open-ended which allowed for several strong suggestions, while mid-20thcentury dynamics was determined by the urge not to repeat the mishaps of a strong national ideology. The current trend seems to lend itself to stronger nationalizing forces in the field of memory politics. The overarching argument of the role played by national museums in the making of the German state and nation is that it has provided a platform for a cultural constitution only slowly negotiating changing ideas of what it means to be German and how to relate to local, regional and transnational communities. Hence, the main impact of the museums is to secure ideas of continuity in the midst of dramatic political change.EuNaMu