96 research outputs found

    The effect of a high-fat diet on brain plasticity, inflammation and cognition in female ApoE4-knockin and ApoE-knockout mice

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    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice

    Caring for the injured : Exploring the immediate and long-term consequences of injury in medieval Cambridge, England

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    Open Access through the Elsevier Agreement Acknowledgments The authors would like to thank Trish Biers of the Duckworth Collection at the University of Cambridge as well as the anonymous reviewers and editors of this special issue (Ileana Mircarelli, Lorna Tilley, and Mary Ann Tafuri) for their comments on this manuscript. This research was generously funded by the Wellcome Trust (Award no 2000368/Z/15/Z) and St John’s College, Cambridge.Peer reviewedPublisher PD

    Van bio-olie tot cosmetica

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    Het raffinageproces waarbij plantaardige oliën worden omgezet tot gebruiksklare producten leidt tot een momenteel onbenutte zijstroom, het ontgeuringsdestillaat. Dit destillaat bevat vrije vetzuren, glyceriden, koolwaterstoffen en minorcomponenten zoals squaleen, sterolen en tocoferolen. Deze laatste kunnen gevaloriseerd worden in de cosmetische, farmaceutische en voedingsindustrie. Daarom is het relevant hun isolatie uit het destillaat te evalueren. Dit kan gebeuren via een superkritische esterificatie gevolgd door een superkritische CO2-extractie. De optimale condities voor beide processen zijn bepaald a.d.h.v. Aspen PlusŸ, een geavanceerd processimulatieprogramma. Op deze manier wordt getracht een conceptueel ontwerp te definiëren voor een economisch rendabele recuperatie van minorcomponenten uit een ontgeuringsdestillaat

    Does Being Defended Relate to Decreases in Victimization and Improved Psychosocial Adjustment Among Victims?

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    School bullying is a clear violation of children’s rights to a safe education and is a major concern among school professionals and parents. Many antibullying interventions focus on enhancing peer defending of victims to combat bullying and to promote victims’ psychosocial functioning. However, longitudinal studies on the effects of being defended on (a) diminishing victimization and (b) enhancing victims’ psychosocial adjustment are lacking, and the role of the broader peer context has been largely unexplored. Therefore, this study examined whether being defended decreases victimization and improves victims’ psychosocial adjustment, and whether defending peer norms moderate these effects. Data were derived from a nationwide Dutch study on the effectiveness of antibullying interventions, with N = 5,415 students (Mage = 9.93; 48.3% girls) from 238 classrooms (54.2% control classrooms) in 68 elementary schools. Findings indicate that victims with at least one defender at the start of the school year (Time 1) experienced higher feelings of belonging at the end of the school year (Time 2) compared with nondefended victims, but experienced lower feelings of belonging compared with nonvictims. Defended victims did not differ from nondefended victims in self-esteem, depressive symptoms, and severity of victimization at Time 2. Nonvictims were significantly better adjusted than defended and nondefended victims regarding these outcomes. Descriptive and popularity norms for defending did not moderate the links between being defended and victims’ adjustment and severity of victimization at Time 2. Thus, being defended only partly relieves victims’ plight, irrespective of how normative defending behaviors are in classrooms. </p

    Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

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    Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso

    Pathways to the medieval hospital : Collective osteobiographies of poverty and charity

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    Medieval hospitals were founded to provide charity, but poverty and infirmity were broad and socially determined categories and little is known about the residents of these institutions and the pathways that led them there. Combining skeletal, isotopic and genetic data, the authors weave a collective biography of individuals buried at the Hospital of St John the Evangelist, Cambridge. By starting with the physical remains, rather than historical expectations, they demonstrate the varied life courses of those who were ultimately buried in the hospital's cemetery, illustrating the diverse faces of medieval poverty and institutional notions of charity. The findings highlight the value of collective osteobiography when reconstructing the social landscapes of the past

    Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.

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    Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.We thank M. Jaeger (Radboudumc) for kindly providing flourescein isothiocyanate-labelled Candida albicans. D. Williams (East Tennessee State University) provided the ÎČ-glucan we used in our initial experiments. H. Lemmers (Radboudumc) kindly prepared the purified lipopolysaccharide used for stimulation of primary human monocytes and macrophages. Part of the figures were prepared using (among other software) Biorender.com. B.N. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (APP1173314). This work was supported by National Institutes of Health grants R01 HL144072, R01 CA220234 and P01 HL131478, as well as a Vici grant from the Dutch Research Council NWO and an ERC Advanced Grant (all to W.J.M.M.). M.G.N. was supported by a Spinoza grant from Dutch Research Council NWO and an ERC Advanced Grant (#833247).S
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