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2. Calorie restriction increases the sensitivity of progeroid Ercc1Δ/−mice to acute (neuro)inflammation

Author

Reitsema, V. A., Schreuder, L., Gerrits, E., Eggen, B. J. L., Goris, M., Laman, J. D., de Rooij, S. E., Wesseling, E. M., Bouma, H. R., and Henning, R. H.

Abstract

Hospitalized elderly patients frequently suffer from delirium, especially in the context of sepsis-associated encephalopathy. Current treatments of delirium are merely symptomatic. Calorie restriction (CR) is both a promising strategy to protect against sepsis and has beneficial effects on aging-induced neurodegeneration. In this study, we investigated whether six weeks of 30% CR had protective effects on lipopolysaccharide (LPS) induced (neuro)inflammation in wild-type (WT) and progeroid mice deficient in the DNA excision-repair gene Ercc1(Ercc1Δ/−). While CR did not affect the LPS-induced inflammatory response in WT mice, CR exaggerated the peripheral inflammatory response in Ercc1Δ/−mice, as evidenced by an increase of pro-inflammatory serum cytokines (TNF-α, IL-1β, and IFN-γ) and kidney injury marker Ngal. Neuroinflammatory effects were assessed by RNA-sequencing of isolated microglia. Similarly, CR did not affect microglia gene expression in WT mice, but increased neuroinflammation-associated gene expression in Ercc1Δ/−mice. In conclusion, CR increases the peripheral and brain inflammatory response of Ercc1Δ/−mice to a systemic inflammatory stimulus.

Published
2024
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5. Negligible Quantities of Particulate Low-Temperature Pyrogenic Carbon Reach the Atlantic Ocean via the Amazon River

Author

Häggi, C., Hopmans, E. C., Schefuss, E., Sawakuchi, A. O., Schreuder, L. T., Bertassoli, D. J. Jr Jr, Chiessi, C. M., Mulitza, S., Sawakuchi, Henrique, Baker, P. A., Schouten, S., Häggi, C., Hopmans, E. C., Schefuss, E., Sawakuchi, A. O., Schreuder, L. T., Bertassoli, D. J. Jr Jr, Chiessi, C. M., Mulitza, S., Sawakuchi, Henrique, Baker, P. A., and Schouten, S.

Abstract

Particulate pyrogenic carbon (PyC) transported by rivers and aerosols, and deposited in marine sediments, is an important part of the carbon cycle. The chemical composition of PyC is temperature dependent and levoglucosan is a source-specific burning marker used to trace low-temperature PyC. Levoglucosan associated to particulate material has been shown to be preserved during riverine transport and marine deposition in high- and mid-latitudes, but it is yet unknown if this is also the case for (sub)tropical areas, where 90% of global PyC is produced. Here, we investigate transport and deposition of levoglucosan in suspended and riverbed sediments from the Amazon River system and adjacent marine deposition areas. We show that the Amazon River exports negligible amounts of levoglucosan and that concentrations in sediments from the main Amazon tributaries are not related to long-term mean catchment-wide fire activity. Levoglucosan concentrations in marine sediments offshore the Amazon Estuary are positively correlated to total organic content regardless of terrestrial or marine origin, supporting the notion that association of suspended or dissolved PyC to biogenic particles is critical in the preservation of PyC. We estimate that 0.5-10 x 10(6) g yr(-1) of levoglucosan is exported by the Amazon River. This represents only 0.5-10 ppm of the total exported PyC and thereby an insignificant fraction, indicating that riverine derived levoglucosan and low-temperature PyC in the tropics are almost completely degraded before deposition. Hence, we suggest caution in using levoglucosan as tracer for past fire activity in tropical settings near rivers., Funding Agencies|European Research Council (ERC) under the European Unions Seventh Framework ProgramEuropean Research Council (ERC) [FP7/2007-2013, 339206]; DFG Excellence ClusterGerman Research Foundation (DFG) [307, KNR/97-4, MSM20/3]; FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/15123-4, 2019/24349-9, 2011/06609-1, 2012/502260-6, 2016/02656-9, 2018/23899-2, 2019/24977-0]; CAPESCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [564/2015, 88881.313535/201901]; CNPqConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [302607/2016-1, 422255/2016-5, 304727/20172]; Alexander von Humboldt FoundationAlexander von Humboldt Foundation; Eidgenossische Technische Hochschule Zurich

Published
2021
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7. Relationships between low-temperature fires, climate and vegetation during three late glacials and interglacials of the last 430 kyr in northeastern Siberia reconstructed from monosaccharide anhydrides in Lake El'gygytgyn sediments

Author

Dietze, E., Mangelsdorf, K., Andreev, A., Karger, C., Schreuder, L., Hopmans, E., Rach, O., Sachse, D., Wennrich, V., and Herzschuh, U.

Abstract

Landscapes in high northern latitudes are assumed to be highly sensitive to future global change, but the rates and long-term trajectories of changes are rather uncertain. In the boreal zone, fires are an important factor in climate–vegetation interactions and biogeochemical cycles. Fire regimes are characterized by small, frequent, low-intensity fires within summergreen boreal forests dominated by larch, whereas evergreen boreal forests dominated by spruce and pine burn large areas less frequently but at higher intensities. Here, we explore the potential of the monosaccharide anhydrides (MA) levoglucosan, mannosan and galactosan to serve as proxies of low-intensity biomass burning in glacial-to-interglacial lake sediments from the high northern latitudes. We use sediments from Lake El'gygytgyn (cores PG 1351 and ICDP 5011-1), located in the far north-east of Russia, and study glacial and interglacial samples of the last 430 kyr (marine isotope stages 5e, 6, 7e, 8, 11c and 12) that had different climate and biome configurations. Combined with pollen and non-pollen palynomorph records from the same samples, we assess how far the modern relationships between fire, climate and vegetation persisted during the past, on orbital to centennial timescales. We find that MAs attached to particulates were well-preserved in up to 430 kyr old sediments with higher influxes from low-intensity biomass burning in interglacials compared to glacials. MA influxes significantly increase when summergreen boreal forest spreads closer to the lake, whereas they decrease when tundra-steppe environments and, especially, Sphagnum peatlands spread. This suggests that low-temperature fires are a typical characteristic of Siberian larch forests also on long timescales. The results also suggest that low-intensity fires would be reduced by vegetation shifts towards very dry environments due to reduced biomass availability, as well as by shifts towards peatlands, which limits fuel dryness. In addition, we observed very low MA ratios, which we interpret as high contributions of galactosan and mannosan from biomass sources other than those currently monitored, such as the moss–lichen mats in the understorey of the summergreen boreal forest. Overall, sedimentary MAs can provide a powerful proxy for fire regime reconstructions and extend our knowledge of long-term natural fire–climate–vegetation feedbacks in the high northern latitudes.

Published
2020

9. The long-term optical evolution of the black hole candidate MAXI J1659−152

Author

Corral-Santana, J.M., Torres, M.A.P., Shahbaz, T., Bartlett, E.S., Russell, D.M., Kong, A.K.H., Casares, J., Muñoz-Darias, T., Bauer, F.E., Homan, J., Jonker, P.G., Sánchez, D. Mata, Wevers, T., Rodríguez-Gil, P., Lewis, F., Schreuder, L., Corral-Santana, J.M., Torres, M.A.P., Shahbaz, T., Bartlett, E.S., Russell, D.M., Kong, A.K.H., Casares, J., Muñoz-Darias, T., Bauer, F.E., Homan, J., Jonker, P.G., Sánchez, D. Mata, Wevers, T., Rodríguez-Gil, P., Lewis, F., and Schreuder, L.

Abstract

Contains fulltext : 184329.pdf (publisher's version ) (Open Access)

Published
2018

15. Methylome analysis of extreme chemoresponsive patients identifies novel markers of platinum sensitivity in high-grade serous ovarian cancer.

Author

Tomar T, Alkema NG, Schreuder L, Meersma GJ, de Meyer T, van Criekinge W, Klip HG, Fiegl H, van Nieuwenhuysen E, Vergote I, Widschwendter M, Schuuring E, van der Zee AGJ, de Jong S, and Wisman GBA

Subjects
Aged, Biomarkers, Tumor, Cisplatin therapeutic use, DNA Methylation, DNA, Neoplasm metabolism, Disease-Free Survival, Epigenesis, Genetic, Female, Humans, Middle Aged, Neoplasm Recurrence, Local, Prospective Studies, Retrospective Studies, Sequence Analysis, DNA, Antineoplastic Agents therapeutic use, Ovarian Neoplasms drug therapy, Platinum Compounds therapeutic use
Abstract

Background: Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients. The objective of this study was to identify and validate novel epigenetic markers of chemoresponse using genome-wide analysis of DNA methylation in extreme chemoresponsive HGSOC patients., Methods: Genome-wide next-generation sequencing was performed on methylation-enriched tumor DNA of two HGSOC patient groups with residual disease, extreme responders (≥18 months progression-free survival (PFS), n = 8) and non-responders (≤6 months PFS, n = 10) to platinum-based chemotherapy. DNA methylation and expression data of the same patients were integrated to create a gene list. Genes were validated on an independent cohort of extreme responders (n = 21) and non-responders (n = 31) using pyrosequencing and qRT-PCR. In silico validation was performed using publicly available DNA methylation (n = 91) and expression (n = 208) datasets of unselected advanced stage HGSOC patients. Functional validation of FZD10 on chemosensitivity was carried out in ovarian cancer cell lines using siRNA-mediated silencing., Results: Integrated genome-wide methylome and expression analysis identified 45 significantly differentially methylated and expressed genes between two chemoresponse groups. Four genes FZD10, FAM83A, MYO18B, and MKX were successfully validated in an external set of extreme chemoresponsive HGSOC patients. High FZD10 and MKX methylation were related with extreme responders and high FAM83A and MYO18B methylation with non-responders. In publicly available advanced stage HGSOC datasets, FZD10 and MKX methylation levels were associated with PFS. High FZD10 methylation was strongly associated with improved PFS in univariate analysis (hazard ratio (HR) = 0.43; 95% CI, 0.27-0.71; P = 0.001) and multivariate analysis (HR = 0.39; 95% CI, 0.23-0.65; P = 0.003). Consistently, low FZD10 expression was associated with improved PFS (HR = 1.36; 95% CI, 0.99-1.88; P = 0.058). FZD10 silencing caused significant sensitization towards cisplatin treatment in survival assays and apoptosis assays., Conclusions: By applying genome-wide integrated methylome analysis on extreme chemoresponsive HGSOC patients, we identified novel clinically relevant, epigenetically-regulated markers of platinum-sensitivity in HGSOC patients. The clinical potential of these markers in predictive and therapeutic approaches has to be further validated in prospective studies.

Published
2017
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16. Pathophysiological and behavioral effects of systemic inflammation in aged and diseased rodents with relevance to delirium: A systematic review.

Author

Schreuder L, Eggen BJ, Biber K, Schoemaker RG, Laman JD, and de Rooij SE

Subjects
Animals, Delirium immunology, Disease Models, Animal, Inflammation immunology, Mice, Rats, Behavior, Animal physiology, Delirium psychology, Inflammation psychology
Abstract

Delirium is a frequent outcome for aged and demented patients that suffer a systemic inflammatory insult. Animal models that reconstruct these etiological processes have potential to provide a better understanding of the pathophysiology of delirium. Therefore, we systematically reviewed animal studies in which systemic inflammation was superimposed on aged or diseased animal models. In total, 77 studies were identified. Aged animals were challenged with a bacterial endotoxin in 29 studies, 25 studies superimposed surgery on aged animals, and in 6 studies a bacterial infection, Escherichia coli (E. coli), was used. Diseased animals were challenged with a bacterial endotoxin in 15 studies, two studies examined effects of the cytokine IL-1β, and one study used polyinosinic:polycytidilic acid (poly I:C). This systematic review analyzed the impact of systemic inflammation on the production of inflammatory and neurotoxic mediators in peripheral blood, cerebrospinal fluid (CSF), and on the central nervous system (CNS). Moreover, concomitant behavioral and cognitive symptoms were also evaluated. Finally, outcomes of behavioral and cognitive tests from animal studies were compared to features and symptoms present in delirious patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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17. Aerobic exercise in children with oxidative phosphorylation defects.

Author

Schreuder L, Peters G, Nijhuis-van der Sanden R, and Morava E

Abstract

Fatigue and exercise intolerance are symptoms in children with metabolic myopathy. Frequently this is combined with muscle pain in children with mitochondrial myopathy. Offering therapeutic advice remains challenging in this patient group. Here we describe five children above the age of four years, with normal intelligence, myopathy, exercise intolerance, motor developmental delay, and fatigue, who were diagnosed with a mitochondrial dysfunction. Based on the positive experience of condition training in adults with mitochondrial disease and inactivity, aerobic exercise training was advised for all the children. Because of the lack of clear protocols for individualized mitochondrial myopathies, regular training was initiated. The Movement Assessment Battery of Children, the Jamar dynamometer for grip force, and the Bruce protocol treadmill test were applied for evaluation. No patient showed significant disease progression on a weekly scheme of strength training or on aerobic training during periods varying between 6 and 18 months. Only one out of the five patients has shown an improvement after a period of structured, aerobic training, demonstrating good compliance and motivation over the course of 18 months. Some patients developed severe muscle pain after explosive exercise. Even in a relatively homogenous, intelligent group of patients and motivated parents, we could not reach full compliance. With our case studies, we would like to draw attention to the importance and pitfalls of movement therapy in children with mitochondrial disease.

Published
2010
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