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Sökning: WFRF:(Holland Eric C)

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1.
  • van Leeuwen, F., et al. (författare)
  • Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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2.
  • Wang, Xiaofeng, et al. (författare)
  • Evidence for type ia supernova diversity from ultraviolet observations with the hubble space telescope
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 749:2, s. 126-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This data set provides unique spectral time series down to 2000 angstrom. Significant diversity is seen in the near-maximum-light spectra (similar to 2000-3500 angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminositiesmeasured in the uvw1/F250W filter are found to correlate with the B-band light-curve shape parameter Delta m(15)(B), but with much larger scatter relative to the correlation in the broadband B band (e.g., similar to 0.4 mag versus similar to 0.2 mag for those with 0.8 mag < Delta m(15)(B) < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by similar to 0.9 mag and similar to 2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.
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3.
  • Alexander, Jes, et al. (författare)
  • Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma
  • 2020
  • Ingår i: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:12, s. 2486-2502
  • Tidskriftsartikel (refereegranskat)abstract
    • Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.
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  • Barna, Barnabas, et al. (författare)
  • SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class
  • 2021
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:1, s. 1078-1099
  • Tidskriftsartikel (refereegranskat)abstract
    • We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax.
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8.
  • Georganaki, Maria, et al. (författare)
  • Tumor endothelial cell up-regulation of IDO1 is an immunosuppressive feed-back mechanism that reduces the response to CD40-stimulating immunotherapy
  • 2020
  • Ingår i: Oncoimmunology. - : TAYLOR & FRANCIS INC. - 2162-4011 .- 2162-402X. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • CD40-stimulating immunotherapy can elicit potent anti-tumor responses by activating dendritic cells and enhancing T-cell priming. Tumor vessels orchestrate T-cell recruitment during immune response, but the effect of CD40-stimulating immunotherapy on tumor endothelial cells has not been evaluated. Here, we have investigated how tumor endothelial cells transcriptionally respond to CD40-stimulating immunotherapy by isolating tumor endothelial cells from agonistic CD40 mAb- or isotype-treated mice bearing B16-F10 melanoma, and performing RNA-sequencing. Gene set enrichment analysis revealed that agonistic CD40 mAb therapy increased interferon (IFN)-related responses in tumor endothelial cells, including up-regulation of the immunosuppressive enzyme Indoleamine 2, 3-Dioxygenase 1 (IDO1). IDO1 was predominantly expressed in endothelial cells within the tumor microenvironment, and its expression in tumor endothelium was positively correlated to T-cell infiltration and to increased intratumoral expression of IFN gamma. In vitro, endothelial cells up-regulated IDO1 in response to T-cell-derived IFN gamma, but not in response to CD40-stimulation. Combining agonistic CD40 mAb therapy with the IDO1 inhibitor epacadostat delayed tumor growth in B16-F10 melanoma, associated with increased activation of tumor-infiltrating T-cells. Hereby, we show that the tumor endothelial cells up-regulate IDO1 upon CD40-stimulating immunotherapy in response to increased IFN gamma-secretion by T-cells, revealing a novel immunosuppressive feedback mechanism whereby tumor vessels limit T-cell activation.
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10.
  • Kaffes, Ioannis, et al. (författare)
  • Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors
  • 2019
  • Ingår i: Oncoimmunology. - : TAYLOR & FRANCIS INC. - 2162-4011 .- 2162-402X. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells in the tumor microenvironment has received increasing attention, especially T cells and tumor-associated macrophages (TAM). The latter are a mixed population of activated brain-resident microglia and infiltrating monocytes/monocyte-derived macrophages, both of which express ionized calcium-binding adapter molecule 1 (IBA1). This study investigated differences in immune cell subpopulations among distinct transcriptional subtypes of GBM. Human GBM samples were molecularly characterized and assigned to Proneural, Mesenchymal or Classical subtypes as defined by NanoString nCounter Technology. Subsequently, we performed and analyzed automated immunohistochemical stainings for TAM as well as specific T cell populations. The Mesenchymal subtype of GBM showed the highest presence of TAM, CD8(+), CD3(+) and FOXP3(+) T cells, as compared to Proneural and Classical subtypes. High expression levels of the TAM-related gene AIF1, which encodes the TAM-specific protein IBA1, correlated with a worse prognosis in Proneural GBM, but conferred a survival benefit in Mesenchymal tumors. We used our data to construct a mathematical model that could reliably identify Mesenchymal GBM with high sensitivity using a combination of the aforementioned cell-specific IHC markers. In conclusion, we demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.
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11.
  • Lindberg, Nanna, et al. (författare)
  • Oncogenic Signaling Is Dominant to Cell of Origin and Dictates Astrocytic or Oligodendroglial Tumor Development from Oligodendrocyte Precursor Cells
  • 2014
  • Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 34:44, s. 14644-14651
  • Tidskriftsartikel (refereegranskat)abstract
    • Stem cells, believed to be the cellular origin of glioma, are able to generate gliomas, according to experimental studies. Here we investigated the potential and circumstances of more differentiated cells to generate glioma development. We and others have shown that oligodendrocyte precursor cells (OPCs) can also be the cell of origin for experimental oligodendroglial tumors. However, the question of whether OPCs have the capacity to initiate astrocytic gliomas remains unanswered. Astrocytic and oligodendroglial tumors represent the two most common groups of glioma and have been considered as distinct disease groups with putatively different origins. Here we show that mouse OPCs can give rise to both types of glioma given the right circumstances. We analyzed tumors induced by K-RAS and AKT and compared them to oligodendroglial platelet-derived growth factor B-induced tumors in Ctv-a mice with targeted deletions of Cdkn2a (p16(Ink4a-/-), p19(Arf-/-), Cdkn2a(-/-)). Our results showed that glioma can originate from OPCs through overexpression of K-RAS and AKT when combined with p19(Arf) loss, and these tumors displayed an astrocytic histology and high expression of astrocytic markers. We argue that OPC shave the potential to develop both astrocytic and oligodendroglial tumors given loss of p19(Arf), and that oncogenic signaling is dominant to cell of origin in determining glioma phenotype. Our mouse data are supported by the fact that human astrocytoma and oligodendroglioma display a high degree of overlap in global gene expression with no clear distinctions between the two diagnoses.
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  • Matthews, Brenda C., et al. (författare)
  • THE AU MIC DEBRIS DISK : FAR-INFRARED AND SUBMILLIMETER RESOLVED IMAGING
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 811:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present far-infrared and submillimeter maps from the Herschel Space Observatory and the James Clerk Maxwell Telescope of the debris disk host star AU Microscopii. Disk emission is detected at 70, 160, 250, 350, 450, 500, and 850 mu m. The disk is resolved at 70, 160, and 450 mu m. In addition to the planetesimal belt, we detect thermal emission from AU Mic's halo for the first time. In contrast to the scattered light images, no asymmetries are evident in the disk. The fractional luminosity of the disk is 3.9 x 10(-4) and its milimeter-grain dust mass is 0.01 M-circle dot (+/- 20%). We create a simple spatial model that reconciles the disk spectral energy distribution as a blackbody of 53 +/- 2K (a composite of 39 and 50 K components) and the presence of small (non-blackbody) grains which populate the extended halo. The best-fit model is consistent with the birth ring model explored in earlier works, i.e., an edge-on dust belt extending from 8.8 to 40 AU, but with an additional halo component with an r(-1.5) surface density profile extending to the limits of sensitivity (140 AU). We confirm that AU Mic does not exert enough radiation force to blow out grains. For stellar mass-loss rates of 10-100 times solar, compact (zero porosity) grains can only be removed if they are very small; consistently with previous work, if the porosity is 0.9, then grains approaching 0.1 mu m can be removed via corpuscular forces (i.e., the stellar wind).
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14.
  • Polyak, Leonid, et al. (författare)
  • History of sea ice in the Arctic
  • 2010
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 29:15-16, s. 1757-1778
  • Tidskriftsartikel (refereegranskat)abstract
    • Arctic sea-ice extent and volume are declining rapidly. Several studies project that the Arctic Ocean may become seasonally ice-free by the year 2040 or even earlier. Putting this into perspective requires information on the history of Arctic sea-ice conditions through the geologic past. This information can be provided by proxy records from the Arctic Ocean floor and from the surrounding coasts. Although existing records are far from complete, they indicate that sea ice became a feature of the Arctic by 47 Ma, following a pronounced decline in atmospheric pCO(2) after the Paleocene-Eocene Thermal Optimum, and consistently covered at least part of the Arctic Ocean for no less than the last 13-14 million years. Ice was apparently most widespread during the last 2-3 million years, in accordance with Earth's overall cooler climate. Nevertheless, episodes of considerably reduced sea ice or even seasonally ice-free conditions occurred during warmer periods linked to orbital variations. The last low-ice event related to orbital forcing (high insolation) was in the early Holocene, after which the northern high latitudes cooled overall, with some superimposed shorterterm (multidecadal to millennial-scale) and lower-magnitude variability. The current reduction in Arctic ice cover started in the late 19th century, consistent with the rapidly warming climate, and became very pronounced over the last three decades. This ice loss appears to be unmatched over at least the last few thousand years and unexplainable by any of the known natural variabilities.
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  • Uhrbom, Lene, et al. (författare)
  • Somatic cell gene transfer
  • 2004
  • Ingår i: Mouse Models Of Human Cancer. - : Wiley-Liss, Inc., Hoboken, New Jersey. - 047144460X ; , s. 474-
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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18.
  • Van Holsbeke, Caroline, et al. (författare)
  • Ultrasound Experience Substantially Impacts on Diagnostic Performance and Confidence when Adnexal Masses Are Classified Using Pattern Recognition
  • 2010
  • Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 69:3, s. 160-168
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To determine how accurately and confidently examiners with different levels of ultrasound experience can classify adnexal masses as benign or malignant and suggest a specific histological diagnosis when evaluating ultrasound images using pattern recognition. Methods: Ultrasound images of selected adnexal masses were evaluated by 3 expert sonologists, 2 senior and 4 junior trainees. They were instructed to classify the masses using pattern recognition as benign or malignant, to state the level of confidence with which this classification was made and to suggest a specific histological diagnosis. Sensitivity, specificity, accuracy and positive and negative likelihood ratios (LR+ and LR-) with regard to malignancy were calculated. The area under the receiver operating characteristic curve (AUC) of pattern recognition was calculated by using six levels of diagnostic confidence. Results: 166 masses were examined, of which 42% were malignant. Sensitivity with regard to malignancy ranged from 80 to 86% for the experts, was 70 and 84% for the 2 senior trainees and ranged from 70 to 86% for the junior trainees. The specificity of the experts ranged from 79 to 91%, was 77 and 89% for the senior trainees and ranged from 59 to 83% for the junior trainees. The experts were uncertain about their diagnosis in 4-13% of the cases, the senior trainees in 15-20% and the junior trainees in 67-100% of the cases. The AUCs ranged from 0.861 to 0.922 for the experts, were 0.842 and 0.855 for the senior trainees, and ranged from 0.726 to 0.795 for the junior trainees. The experts suggested a correct specific histological diagnosis in 69-77% of the cases. All 6 trainees did so significantly less often (22-42% of the cases). Conclusion: Expert sonologists can accurately classify adnexal masses as benign or malignant and can successfully predict the specific histological diagnosis in many cases. Whilst less experienced operators perform reasonably well when predicting the benign or malignant nature of the mass, they do so with a very low level of diagnostic confidence and are unable to state the likely histology of a mass in most cases. Copyright (C) 2009 S. Karger AG, Basel
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19.
  • Villanueva, Josep, et al. (författare)
  • Differential exoprotease activities confer tumor-specific serum peptidome patterns
  • 2006
  • Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 116:1, s. 271-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have established distinctive serum polypeptide patterns through mass spectrometry (MS) that reportedly correlate with clinically relevant outcomes. Wider acceptance of these signatures as valid biomarkers for disease may follow sequence characterization of the components and elucidation of the mechanisms by which they are generated. Using a highly optimized peptide extraction and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) MS-based approach, we now show that a limited subset of serum peptides (a signature) provides accurate class discrimination between patients with 3 types of solid tumors and controls without cancer. Targeted sequence identification of 61 signature peptides revealed that they fall into several tight clusters and that most are generated by exopeptidase activities that confer cancer type-specific differences superimposed on the proteolytic events of the ex vivo coagulation and complement degradation pathways. This small but robust set of marker peptides then enabled highly accurate class prediction for an external validation set of prostate cancer samples. In sum, this study provides a direct link between peptide marker profiles of disease and differential protease activity, and the patterns we describe may have clinical utility as surrogate markers for detection and classification of cancer. Our findings also have important implications for future peptide biomarker discovery efforts.
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20.
  • Wallmann, Tatjana, et al. (författare)
  • Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity
  • 2018
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 9, s. 71-83
  • Tidskriftsartikel (refereegranskat)abstract
    • High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma. Here we show that the spatial location of TAMMs correlates with the expansion of a subset of tumor cells that have acquired expression of PDGFRB in both mouse and human low-grade glioma and HCGs. Furthermore, M2-polarized microglia but not bone marrow (BM)-derived macrophages (BMDMs) induced PDGFRB expression in glioma cells and stimulated their migratory capacity. These findings illustrate a heterotypic cross-talk between microglia and glioma cells that may enhance the migratory and invasive capacity of the latter by inducing PDGFRB.
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21.
  • Wee, Boyoung, et al. (författare)
  • ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.
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22.
  • Wolf, Rebecca M., et al. (författare)
  • p190RhoGAP can act to inhibit PDGF-induced gliomas in mice : a putative tumor suppressor encoded on human chromosome 19q13.3.
  • 2003
  • Ingår i: Development, Genes and Evolution. - : Cold Spring Harbor Laboratory. - 0949-944X .- 1432-041X. ; 17:4, s. 476-487
  • Tidskriftsartikel (refereegranskat)abstract
    • p190RhoGAP and Rho are key regulators of oligodendrocyte differentiation. The gene encoding p190RhoGAP is located at 19q13.3 of the human chromosome, a locus that is deleted in 50%-80% of oligodendrogliomas. Here we provide evidence that p190RhoGAP may suppress gliomagenesis by inducing a differentiated glial phenotype. Using a cell culture model of autocrine loop PDGF stimulation, we show that reduced Rho activity via p190RhoGAP overexpression or Rho kinase inhibition induced cellular process extension, a block in proliferation, and reduced expression of the neural precursor marker nestin. In vivo infection of mice with retrovirus expressing PDGF and the p190 GAP domain caused a decreased incidence of oligodendrogliomas compared with that observed with PDGF alone. Independent experiments revealed that the retroviral vector insertion site in 3 of 50 PDGF-induced gliomas was within the p190RhoGAP gene. This evidence strongly suggests that p190 regulates critical components of PDGF oncogenesis and can act as a tumor suppressor in PDGF-induced gliomas by down-regulating Rho activity.
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23.
  • Yeung, Edwina, et al. (författare)
  • Maternal age is related to offspring DNA methylation : a meta-analysis of results from the pace consortium
  • 2024
  • Ingår i: Aging Cell. - : John Wiley & Sons. - 1474-9718 .- 1474-9726.
  • Tidskriftsartikel (refereegranskat)abstract
    • Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5–10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10−8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
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