298 research outputs found

    Proteome analysis of monocytes implicates altered mitochondrial biology in adults reporting adverse childhood experiences.

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    The experience of adversity in childhood has been associated with poor health outcomes in adulthood. In search of the biological mechanisms underlying these effects, research so far focused on alterations of DNA methylation or shifts in transcriptomic profiles. The level of protein, however, has been largely neglected. We utilized mass spectrometry to investigate the proteome of CD14(+) monocytes in healthy adults reporting childhood adversity and a control group before and after psychosocial stress exposure. Particular proteins involved in (i) immune processes, such as neutrophil-related proteins, (ii) protein metabolism, or (iii) proteins related to mitochondrial biology, such as those involved in energy production processes, were upregulated in participants reporting exposure to adversity in childhood. This functional triad was further corroborated by protein interaction- and co-expression analyses, was independent of stress exposure, i.e. observed at both pre- and post-stress time points, and became evident especially in females. In line with the mitochondrial allostatic load model, our findings provide evidence for the long-term effects of childhood adversity on mitochondrial biology

    Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease

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    Introduction Neuroinflammation and synaptic degeneration are major neuropathological hallmarks in Alzheimer’s disease (AD). Neurogranin and YKL-40 in cerebrospinal fluid (CSF) are newly discovered markers indicating synaptic damage and microglial activation, respectively. Methods CSF samples from 95 individuals including 39 patients with AD dementia (AD-D), 13 with mild cognitive impairment (MCI) due to AD (MCI-AD), 29 with MCI not due to AD (MCI-o) and 14 patients with non-AD dementias (non-AD-D) were analyzed for neurogranin and YKL-40. Results Patients with dementia or MCI due to AD showed elevated levels of CSF neurogranin (p < 0.001 for AD-D and p < 0.05 for MCI-AD) and YKL-40 (p < 0.05 for AD-D and p = 0.15 for MCI-AD) compared to mildly cognitively impaired subjects not diagnosed with AD. CSF levels of neurogranin and YKL-40 did not differ between MCI not due to AD and non-AD dementias. In AD subjects no correlation between YKL-40 and neurogranin was found. The CSF neurogranin levels correlated moderately with tau and p-tau but not with Aβ42 or the MMSE in AD samples. No relevant associations between YKL-40 and MMSE or the core AD biomarkers, Aβ42, t-tau and p-tau were found in AD subjects. Conclusions Neurogranin and YKL-40 are promising AD biomarkers, independent of and complementary to the established core AD biomarkers, reflecting additional pathological changes in the course of AD

    Long-lived spin waves in a metallic antiferromagnet

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    Collective spin excitations in magnetically ordered crystals, called magnons or spin waves, can serve as carriers in novel spintronic devices with ultralow energy consumption. The generation of well-detectable spin flows requires long lifetimes of high-frequency magnons. In general, the lifetime of spin waves in a metal is substantially reduced due to a strong coupling of magnons to the Stoner continuum. This makes metals unattractive for use as components for magnonic devices. Here, we present the metallic antiferromagnet CeCo2P2, which exhibits long-living magnons even in the terahertz (THz) regime. For CeCo2P2, our first-principle calculations predict a suppression of low-energy spin-flip Stoner excitations, which is verified by resonant inelastic X-ray scattering measurements. By comparison to the isostructural compound LaCo2P2, we show how small structural changes can dramatically alter the electronic structure around the Fermi level leading to the classical picture of the strongly damped magnons intrinsic to metallic systems. Our results not only demonstrate that long-lived magnons in the THz regime can exist in bulk metallic systems, but they also open a path for an efficient search for metallic magnetic systems in which undamped THz magnons can be excited.This work was supported by the German Research Foundation (DFG) through Grants No. KR3831/5-1, No. LA655/20-1m, Fermi-NEst, GRK1621, TRR288 (No. 422213477) project A03, and SFB1143 (No. 247310070). D.V.V. acknowledges support from the Spanish Ministry of Science and Innovation, project PID2020-116093RB-C44, funded by MCIN/AEI/10.13039/ 501100011033. A.E. acknowledges funding by Fonds zur Förderung der wissenschaftlichen Forschung (FWF) grant I 5384. Part of the calculations were performed at Rechenzentrum Garching of the Max Planck Society (Germany). The authors acknowledge the ESRF for beamtime on beamline ID32.Peer reviewe

    Sektoralisierung als Planungsherausforderung im inklusiven Gemeinwesen

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    2. Hrsg.: Martin F. Reichstein Förderung durch: Forschungsinstitut für gesellschaftliche Weiterentwicklung (FGW)Seit September 2016 führt das Zentrum für Planung und Evaluation Sozialer Dienste (ZPE) der Universität Siegen das Forschungsprojekt „Koordinationspotenziale kommunaler Teilhabepolitik in der Pflege, Behindertenhilfe und Sozialpsychiatrie (KoKoP)“ durch. Das Projekt wird im Rahmen des Programms „Vorbeugende Sozialpolitik“ des nordrheinwestfä- lischen Forschungsinstituts für Gesellschaftliche Weiterentwicklung (FGW) finanziell gefördert. Ziel des Projektes ist es, anhand empirischer Untersuchungen Erkenntnisse darüber zu gewinnen, welche Möglichkeiten für Kommunen bestehen, durch Planung und Koordination die Wirkungen von Teilhabeleistungen in den Leistungsbereichen der Pflege, Behindertenhilfe und Sozialpsychiatrie zu optimieren. Zudem soll der Frage nachgegangen werden, wie professionelle Hilfen stärker mit informellen Ressourcen im Vor- und Umfeld des Leistungsgeschehens verknüpft werden können. Mögliche Problemquellen werden u.a. in einer ausgeprägten Sektoralisierung des Leistungsgeschehens, mangelnder Kooperation sowie in einer geringen Sozialraumorientierung vermutet. Im Rahmen eines eintägigen Expertenworkshops am 14. November 2017 wurden zum einen Zwischenergebnisse bisheriger Untersuchungen vorgestellt und diskutiert. Zum anderen wurden in drei Arbeitsgruppen zentrale Fragestellungen des Projekts erörtert. Der vorliegende Band ist eine Zusammenschau von Beiträgen einzelner Teilnehmer*innen dieses Workshops

    Economic Analysis of Knowledge: The History of Thought and the Central Themes

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    Following the development of knowledge economies, there has been a rapid expansion of economic analysis of knowledge, both in the context of technological knowledge in particular and the decision theory in general. This paper surveys this literature by identifying the main themes and contributions and outlines the future prospects of the discipline. The wide scope of knowledge related questions in terms of applicability and alternative approaches has led to the fragmentation of research. Nevertheless, one can identify a continuing tradition which analyses various aspects of the generation, dissemination and use of knowledge in the economy

    Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

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    BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

    Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

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