Neuronal microRNA eeregulation in response to Alzheimer's disease Amyloid-β

Normal brain development and function depends on microRNA (miRNA) networks to fine tune the balance between the transcriptome and proteome of the cell. These small non-coding RNA regulators are highly enriched in brain where they play key roles in neuronal development, plasticity and disease. In neurodegenerative disorders such as Alzheimer's disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, and addresses the hypothesis that amyloid-beta (Abeta) itself, a known causative factor of AD, causes neuronal miRNA deregulation, which could contribute to the pathomechanisms of AD. We used sensitive TaqMan low density miRNA arrays (TLDA) on murine primary hippocampal cultures to show that about half of all miRNAs tested were down-regulated in response to Abeta peptides. Time-course assays of neuronal Abeta treatments show that Abeta is in fact a powerful regulator of miRNA levels as the response of certain mature miRNAs is extremely rapid. Bioinformatic analysis predicts that the deregulated miRNAs are likely to affect target genes present in prominent neuronal pathways known to be disrupted in AD. Remarkably, we also found that the miRNA deregulation in hippocampal cultures was paralleled in vivo by a deregulation in the hippocampus of Abeta42-depositing APP23 mice, at the onset of Abeta plaque formation. In addition, the miRNA deregulation in hippocampal cultures and APP23 hippocampus overlaps with those obtained in human AD studies. Taken together, our findings suggest that neuronal miRNA deregulation in response to an insult by Abeta may be an important factor contributing to the cascade of events leading to AD.N.S. is supported by the Human Frontier Science Program. L.I. is supported by the National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC), and J.G. is supported by grants from the University of Sydney, the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), and the J.O. & J.R. Wicking Trust. Postgraduate scholarship support has been provided by the Wenkart Foundation, GlaxoSmithKline and Alzheimer’s Australia

Urban Heat Islands Strategy Plan Vienna – Implementing Urban Green Infrastructure to Reduce Negative Effects of Urban Heat Islands

Urban heat islands (UHI) have been known since the 19th century (Howard, 1820) and describe the difference in temperature between cities and their rural surroundings. This difference can be up to 12°C (Eliasson, 2000, 31); the phenomenon is caused by the transformation of natural surfaces through e.g. soil sealing, construction of infrastructure and buildings. However, differences in temperature not only occur between cities and their adjacent areas, but also within different parts of cities depending on the provision of green and blue infrastructure as well as on their share of sealed surfaces. The situation is further aggravated by a changing climate. Numerous studies state that the number of heat days (maximum temperature of at least 30°C) as well as the number and duration of heat waves will increase worldwide – especially in cities due to their sealed surfaces, building density and lack of green space (Formayer et al., 2008; Bowler et al., 2010). This problem will become even more crucial in the future: in 2005 approx. half of the world population lived in urban regions and this number is predicted to rise by up to nearly two thirds by 2050 (Schlünzen, 2012). Consequences of those growing cities and expanding urban areas are further densification of settlement areas and loss of open and green space; this strengthens the urban heat islands effect even more. Urban heat islands can have negative effects on human health and wellbeing with sensitive groups such as the elderly being especially affected (Allex et al., 2013). To counteract UHI and their negative effects, the “Urban Heat Islands Strategy Plan Vienna” has been elaborated as part of a Central Europe project (www.http://eu-uhi.eu/, 2011-2014). The aim was the development of a strategy for the City of Vienna to implement open space planning as well as urban ecology measures to reduce the negative aspects of UHI. Within the project, a guideline has been elaborated by the project team and members of the Environmental Protection Department Vienna (MA 22) to support planners, architects as well as members of the Vienna City Administration, to show possibilities of technical and strategic measures against UHI as well as their potential to reduce urban heat, and to point out planning tools and planning levels. The guideline is available online (https://www.wien.gv.at/umweltschutz/raum/uhi-strategieplan.html, in German)

Urban green infrastructure planning as a contribution to the smart ‘green’ city

The urban green infrastructure is getting due to the strong growth of the City of Vienna under increasing pressure. A foresighted planning of green and open spaces is necessary to obtain the different "Ecosytem Services" - provision-related services, regulatory services, cultural services and support services (MEA 2005). Additionally an increase in the number of hot days and thus an increase of the heat load in the city is predicted for Vienna (ZAMG 2012). Again, making a foresighted planning of green and open spaces is a significant contribution to meet these climatic challenges (Kuffner A. 2012, Hagen et al. 2010). Based on the concept of "green infrastructure" (Pauleit et al. 2011) and the ecosystem services of these, it is shown which contribution - in particular to reduce the heating of the city - they can make to the Smart City concept

Test Performance Characteristics of Anti-HEV IgG Assays Strongly Influence Hepatitis E Seroprevalence Estimates

Hepatitis E virus (HEV) seroprevalences of 0.3%–53% were reported from industrialized countries. Because these estimates may be influenced by detection assays, this study compares 3 frequently used tests for HEV detection: the MP Diagnostics HEV immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), the Axiom Diagnostics HEV IgG enzyme immunoassay (EIA), and the Mikrogen recomLine HEV IgG assay. Sera from 200 healthy healthcare workers and 30 individuals with acute HEV infection were analyzed. Among the healthy individuals, HEV IgG was found in 4.5% by the MP Diagnostics assay, in 29.5% by the Axiom Diagnostics assay, and in 18% by the Mikrogen assay. Among individuals with acute HEV infection, positive results were obtained for 83.3%, 100%, and 96.7%, respectively. Thus, the 3 assays show clear differences in diagnostic sensitivity

Neuronal MicroRNA Deregulation in Response to Alzheimer's Disease Amyloid-β

Normal brain development and function depends on microRNA (miRNA) networks to fine tune the balance between the transcriptome and proteome of the cell. These small non-coding RNA regulators are highly enriched in brain where they play key roles in neuronal development, plasticity and disease. In neurodegenerative disorders such as Alzheimer's disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, and addresses the hypothesis that amyloid-β (Aβ) itself, a known causative factor of AD, causes neuronal miRNA deregulation, which could contribute to the pathomechanisms of AD. We used sensitive TaqMan low density miRNA arrays (TLDA) on murine primary hippocampal cultures to show that about half of all miRNAs tested were down-regulated in response to Aβ peptides. Time-course assays of neuronal Aβ treatments show that Aβ is in fact a powerful regulator of miRNA levels as the response of certain mature miRNAs is extremely rapid. Bioinformatic analysis predicts that the deregulated miRNAs are likely to affect target genes present in prominent neuronal pathways known to be disrupted in AD. Remarkably, we also found that the miRNA deregulation in hippocampal cultures was paralleled in vivo by a deregulation in the hippocampus of Aβ42-depositing APP23 mice, at the onset of Aβ plaque formation. In addition, the miRNA deregulation in hippocampal cultures and APP23 hippocampus overlaps with those obtained in human AD studies. Taken together, our findings suggest that neuronal miRNA deregulation in response to an insult by Aβ may be an important factor contributing to the cascade of events leading to AD

EUROSPINE 2017 FULL PAPER AWARD: Time to remove our rose-tinted spectacles: a candid appraisal of the relative success of surgery in over 4500 patients with degenerative disorders of the lumbar spine, hip or knee

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Methodische Grundlagen für sozio-ökonomische Analysen sowie Folgenabschätzungen von Maßnahmen einschließlich Kosten-Nutzen Analysen nach EG-Meeresstrategie-Richtlinie (MSRL) - Abschlussbericht -

Die Meeresstrategie-Rahmenrichtlinie (MSRL) will durch gezielte Maßnahmen bis 2021 den guten Umweltzustand in den europäischen Meeren erreichen. Dazu sind die Kosten und die Nutzen derartiger Schutzmaßnahmen zu ermitteln und abzuwägen. Die Ziele des Forschungsprojektes waren deshalb zweierlei: zum einen der Frage nachzugehen, welche ökonomischen Nutzen durch Maßnahmen zur Belastungsreduktion entstehen, und zum anderen zu untersuchen, wie die Nutzen einer Maßnahme zur Verbesserung der Meeresumwelt nach heutigem Wissensstand quantifiziert werden können. Mit der Kostenseiten befasst sich das Vorhaben nicht. Um die genannten Ziele zu erreichen, wurden im Projekt methodische Grundlagen und darauf basierend ein Mengengerüst zur Monetarisierung von ökonomischen Nutzen durch maritime Schutzmaßnahmen im Rahmen der MSRL-Implementierung entwickelt. Dieses methodische Vorgehen ist daraufhin in zwei Fallstudien (zur Müllreduzierung in der Nordsee und zur Eutrophierungsreduzierung in der Ostsee) auf seine Praktikabilität und Einfachheit hin getestet worden, um die Ergebnisse in die Entwicklung einer praktikablen Handlungsanleitung einfließen zu lassen. Flankierend wurde im Rahmen des Projekts eine Zahlungsbereitschaftsanalyse zur Eutrophierungsreduktion in der Ostsee durchgeführt, deren Ergebnisse in die Arbeiten des internationalen Forschungsnetzwerks BalticSTERN sowie in einer der o.g. Fallstudien eingeflossen sind. Die Ergebnisse des Vorhabens waren demnach eine Abschätzung der Nutzen durch Reduktionsmaßnahmen der Belastungen "Mariner Abfall" und "Eutrophierung", sowie eine Diskussion der damit verbundenen Unsicherheiten und Datenlücken. Außerdem ist über die Zahlungsbereitschaftsanalyse die Wertschätzung der deutschen Bevölkerung für eine Reduzierung der Eutrophierung der Ostsee erhoben worden. Die Erkenntnisse, die im Rahmen des Projektes gesammelt wurden, sind schließlich in die Handlungsanleitung eingeflossen