Cerebrospinal Fluid Tau, p-Tau 181 and Amyloid-beta(38/40/42) in Frontotemporal Dementias and Primary Progressive Aphasias

Background/Aims: We determined cerebrospinal fluid (CSF) concentrations of amyloid-beta(A beta)(1-38), A beta(1-40), A beta(1-42), total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer's dementia (AD, n = 25) and nondemented controls (n = 20). Methods: Commercially available ELISA and electrochemiluminescence methods were applied. Results: High CSF p-tau and low ratios of A beta(1-42)/A beta(1-40) and A beta(1-42)/A beta(1-38), respectively, were specific for AD. CSF A beta(1-38) was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD. Conclusion: This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations. Copyright (C) 2010 S. Karger AG, Base

Der König als Krieger. Zum Verhältnis von Königtum und Krieg im Mittelalter. Beiträge der Tagung des Zentrums für Mittelalterstudien der Otto-Friedrich-Universität Bamberg (13. – 15. März 2013)

Der König als Krieger – Zum Verhältnis von Königtum und Krieg im Mittelalter Kriegshandlungen waren in der mittelalterlichen Gesellschaft allgegenwärtig und oftmals eng mit dem Königtum verknüpft. Nahezu alle Könige des Mittelalters haben während ihrer Regierungszeit militärische Aktionen durchgeführt. Dabei agierten sie als Kriegsherren, militärische Anführer und immer wieder auch als aktive Kämpfer. Diese Rollen werden in den Quellen oft genug betont, etwa durch den gängigen Topos einer mitreißenden Rede unmittelbar vor der Schlacht. Gleichzeitig waren sich die Zeitgenossen jedoch der Bedeutung der persönlichen Unversehrtheit des Monarchen vollauf bewusst, womit ein Spannungsmoment zwischen der Herrschertugend der Tapferkeit (fortitudo) und der Raison des Königsamtes gegeben war. Der Sammelband analysiert anhand von verschiedenen historischen Beispielen, welche Bedeutung die Kriegsteilnahme für das mittelalterliche Herrschaftsverständnis hatte, wann, wie und in welchem Kontext die Rolle des Königs als Feldherr oder Kämpfer besonders hervorgehoben, wann sie unterdrückt oder kritisiert wurde

Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)

This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014–2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000–2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.This work received external funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032 and received co-funding from the author’s organizations. The Norwegian Institute of Public Health (NIPH) contributed to the funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements were partly funded by the Research Council of Norway through research projects (275903 and 268465).info:eu-repo/semantics/publishedVersio

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10−12). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10−5), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10−3). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-4

EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

Funding Information: The authors would like to thank everybody who contributed to the HBM4EU Aligned Studies: the participating children, teenagers, adults and their families, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the HBM4EU project partners, especially those from WP7 for developing all materials supporting the fieldwork, WP9 for organizing the QA/QC scheme under HBM4EU and all laboratories who performed the analytical measurements. We would like to acknowledge Sun Kyoung Jung from the National Institute of Environmental Research of South-Korea for providing the KoNEHS Cycle III results (crt adjusted). HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principal investigators of the contributing studies for their participation and contribution to the HBM4EU Aligned Studies and the national program owners for their financial support. Further details on funding for all the participating studies can be found in the Supplemental Material, Table S12.As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.publishersversionpublishe

Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032).As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants from three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years, and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, and benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs, and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with the highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European-wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability, and will give leverage to national policymakers for the implementation of targeted measures.info:eu-repo/semantics/publishedVersio

Das geplante Göttinger Promotionsprogramm zur "Materialität des Wissens" zwischen Interdisziplinarität und Transdisziplinarität

Für die Aus- und Weiterbildung des wissenschaftlichen Nachwuchses bieten die Objekte der universitären Sammlungen ein besonderes Potential, das bisher jedoch nur in wenigen Fachdisziplinen genutzt wird. Den intensiv geführten theoretischen Debatten der Sozial- und Kulturwissenschaften über die Bedeutung der Materialität für die Formierung und Transformation von Wissensbeständen steht bislang eine verhältnismäßig geringe Zahl an empirischen Arbeiten gegenüber, die dieses Erkenntnispotential auch am konkreten Einzelfall und für bestimmte Zeiträume zu nutzen versuchen. Ein Grund für diese Zurückhaltung mag in den besonderen Anforderungen an eine konkrete Auseinandersetzung mit den Objekten der Wissenschaften liegen. Denn neben der Kenntnis der theoretischen Grundlagen der Materialitäts- und Wissensforschung bedarf es der jeweils fachspezifischen Kompetenz im Umgang mit den Objekten, die für die Erschließung der dinglichen Dimension von Wissen und Wissenschaft notwendig ist. Die Universität Göttingen plant daher in Kooperation mit der Hochschule für angewandte Wissenschaft und Kunst in Hildesheim ein Promotionsprogramm, das sich zum einen an Promovierende mit einem Studienabschluss in den Geistes-, Gesellschafts- und Naturwissenschaften richtet. Zum anderen soll es Absolvent_innen der stärker praxis- und materialbezogenen Studiengänge ansprechen, wie etwa Restaurierung, Gestaltung und Museumskunde. Es wird damit zwei zentrale Fragehorizonte verknüpfen, die bisher disziplinär wie institutionell weitgehend getrennt voneinander erforscht werden: die Frage nach der jeweiligen Materialität akademischen Wissens auf der einen Seite und das Wissen über die materielle Beschaffenheit sowie die Techniken ihrer Bearbeitung in den verschiedenen Fächern auf der anderen Seite. Der vorliegende Beitrag möchte eine Diskussion über die fachlichen Anforderungen und institutionellen Grenzen anregen, die sich dem objektorientierten Forschen und Lernen sowohl zwischen als auch jenseits der Disziplinen stellen

Production, perception et contrôle de l’espace dans la « Première ligue des villes souabes » (1376-1390)

En 1388, les conflits longtemps latents entre les ducs de Bavière et les membres de la ligue urbaine souabe finirent par mener à une guerre, communément désignée comme la « Première guerre des villes d’Allemagne du Sud ». Ainsi, la catégorie spatiale « Allemagne du Sud », qui renvoie à un espace vaste mais sans limites claires, servit à donner un nom à un événement historique. Ce dernier n’attira cependant pas autant l’attention des historiens que l’appellation ne pouvait le laisser supposer...