The effect of lifestyle intervention in obesity on the soluble form of activated leukocyte cell adhesion molecule

Background: The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters. Methods: Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated. Results: At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline. Conclusions: sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions. Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Helden in der Schule. Akten der Tagung Kloster Banz 2014

Ausgehend von der Feststellung, dass die Integration mittelalterlicher Texte im Deutschunterricht in der Schulpraxis weitgehend ein Desiderat darstellt, präsentierten Beitragende aus Schule und Wissenschaft bei der Tagung „Helden in der Schule“ im Oktober 2014 ihre Projekte und Ideen zu und Erfahrungen mit der Implementation germanistisch-mediävistischer Inhalte im Deutschunterricht. Dabei reichen die Beiträge von allgemeinen Überlegungen zum Nutzen mittelalterlicher Literatur in der Schule über konkrete Unterrichtsentwürfe bis hin zur Umsetzung in der Waldorfschule und der Integration schulbezogener Lehrveranstaltungen in der Universität. Bei aller Verschiedenheit in den Herangehensweisen wird in allen Beiträgen eindrucksvoll deutlich gemacht, dass mittelalterliche Literatur auch im 21. Jahrhundert überaus lohnend in die Unterrichtspraxis einbezogen werden kann.Since medieval texts are not treated enough in school, lecturers working in school and university presented their projects, ideas and experiences concerning the implementation of German-mediavistic contents in German school lessons during the conference “Heroes in School” in October 2014. The topics concern general reflection about the profitability of medieval literature in school, concrete lesson plans, the implementation in Rudolf Steiner schools, the integration of seminars in university that deal with the work in school etc. All articles demonstrate that the integration of medieval literature in school worth the effort – also in the 21st century

The ambulant National Socialist exhibition "Neue deutsche Baukunst" and her reception in Portugal (1941)

"Ein wirklich künstlerisches Ereignis": So titelten zahlreiche portugiesische Zeitungen im November 1941, um über die deutsche Architekturausstellung zu berichten, die in Lissabon für zwei Wochen einen regelrechten Besucheransturm auslöste. Spätere Historiker schreiben deshalb der Exposition eine gewisse Vorbildfunktion für die portugiesische Bautätigkeit der 1940er Jahre zu. Ausgehend von dieser These widmet sich die vorliegende Studie, erstmalig im deutschsprachigen Raum, der vollständigen Rekonstruktion der nationalsozialistischen Wanderausstellung "Neue Deutsche Baukunst". Wie sich nach anfänglichen Recherchen herausstellte, gastierte die Schau nicht nur in Lissabon, sondern wurde zwischen 1940 und 1943 an insgesamt zehn europäischen Orten präsentiert. Deshalb steht neben der Rezeption in Portugal, auch die Ausstellung selbst im Mittelpunkt der Untersuchung. Im ersten Teil der Arbeit wird zunächst auf den allgemeinen Verlauf der Wanderausstellung, ihren Aufbau und ihre Organisationsstruktur eingegangen. In diesem Kontext spielt die Analyse der Entstehungsgeschichte der Ausstellung, besonders im Hinblick auf ihre Konzeption, eine wichtige Rolle. Der zweite Teil der Untersuchung liefert dann eine umfangreiche Betrachtung der Exposition in Lissabon (08.-16. November 1941), wobei auf die Rahmenbedingungen, die Durchführung sowie die Gestaltung Bezug genommen wird. Schließlich werden auf der Grundlage eines detaillierten Studiums der Rezensionslage richtungsweisende Perspektiven bezüglich der Ausstellungsrezeption durch portugiesische Architekten aufgezeigt."A real artistic event": this is how many Portuguese newspapers headlined in November 1941 to cover the German architecture exhibition in Lisbon which had caused a rush of visitors for two weeks. Later historians therefore consider the exposition a model example for Portuguese building of the 1940s. On the basis of this thesis, the present study, for the first time in the German-speaking world, attends to completely reconstruct the ambulant National Socialist exhibition "Neue Deutsche Baukunst". After initial research it showed that the exhibition has not only been presented in Lisbon, but also in ten other European locations between 1940 and 1943. Thus, next to its reception in Portugal, the exhibition itself stands in the focus of the study. The first part of this work deals with the general process of the touring exhibition, its setup and organizational structure. In this context, the analysis of the exhibition's history, especially with regard to its conception, plays an important role. The second part of the examination provides an extensive reflection of the exposition in Lisbon (8 - 16 November 1941) and also refers to the basic conditions, realization and design. Finally, on the basis of a detailed study of reviews, trend-setting perspectives concerning the reception of the exhibition by Portuguese architects are shown. ------------------------------------------------------------------------------- português: Em Novembro de 1941, os jornais portugueses consideraram a exposição "Nova Arquitectura Alemã" que na altura estava patente em Lisboa como "um verdadeiro acontecimento artístico". A exposição, que teve muita afluência de público, influenciou, segundo alguns historiadores, a arquitectura de obras públicas portuguesas dos anos 40. Partindo desta perspectiva, esta tese procura levar a cabo, pela primeira vez, uma reconstrução histórica da exposição itinerante "Nova Arquitectura Alemã". Segundo algumas pesquisas feitas, a exposição terá tido lugar entre 1940 e 1943, não só em Lisboa, mas em dez cidades europeias. Neste contexto, este trabalho centra-se no percurso completo da exposição. A primeira parte da investigação aborda o percurso global da exposição, a sua constituição e estrutura de organização, com especial incidência para a história da sua formação e para a sua concepção. A segunda parte centra-se na exposição de Lisboa (patente de 8 a 16 Novembro de 1941), nas suas condições gerais, realização e representação. Na sua última parte, a tese analisa diferentes perspectivas e olhares críticos de arquitectos portugueses sobre a exposição que darão certas indicações à recepção desta exposição nas obras públicas portuguesa dos anos 40

Kapitel 10. Integrierte Perspektiven auf Strukturbedingungen

Strukturen wirken auf vielfältige Weise auf alltägliches Handeln und ihre adäquate Gestaltung ist daher notwendig, um klimafreundliches Verhalten dauerhaft zu ermöglichen. Die in Abschnitt 3 behandelten Strukturen fördern oder behindern eine Transformation in Richtung klimafreundli-chen Lebens maßgeblich und sind quer durch alle Handlungsfelder von Relevanz. Die einzelnen Strukturen, deren Analyse sich so weit möglich auf die besonderen Bedingungen in Österreich bezieht, thematisieren unterschiedliche Bereiche, die von Strukturveränderungen betroffen sind: Recht, Governance, Strukturen der öffentlichen Willensbildung in Diskursen und Medien sowie in Bildung und Wissensproduktion als auch wirtschaftliche Aktivitäten einschließlich ihrer tech-nischen Dimensionen und der zugehörigen Innovationssysteme. Ebenso werden Bereiche wie räumliche Ungleichheit und Raumplanung sowie soziale Sicherungssysteme in den Blick ge-nommen. Der Abschnitt betrachtet zudem die Versorgung mit Gütern und Dienstleitungen gene-rell, legt aber auch einen Akzent auf globalisierte Warenketten und Geld- und Finanzsysteme, um die interdependenten Strukturen über die Grenzen Österreichs hinaus zu thematisieren. Die strukturierende Rolle der gebauten Umwelt wird im abschließenden Kapitel zu netzgebundenen Infrastrukturen diskutiert

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

BackgroundProtein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. ObjectiveWe sought to characterize the role of EIF4A2 variants in dystonic conditions. MethodsWe undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. ResultsWe report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. ConclusionsOur findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. & COPY;2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society