399 research outputs found
NK cells and T cells: mirror images?
No full textThe expression of MHC class I molecules protects cells against lysis by natural killer (NK) cells. It is possible that NK cells are 'educated' to recognize self MHC class I molecules and that the combination of self peptide and MHC class I molecule blocks NK-mediated lysis. Here, Rogier Versteeg compares and contrasts models of education and self-nonself discrimination by T cells and NK cells, and presents a hypothesis for the evolution of T cells from NK cell
Sketch of the Early History of the Reformed Dutch Church of Bergen in Jersey City
No full textHistory of the Reformed Dutch Church of Bergen, which served the colonial populations of what is now Hudson and Bergen counties as well as Staten Island. Describes growth of the church in economic terms as well as church membership, the roles of officials, and services to the membership.The Settlement of Bergen; The School; The Church; The Membership; The Consistory; Baptisms; Marriages; Burials; Religious Services and the Lord's Supper; Receipts and Expenditures; The Voorleezer, The Ministe
Experimenteren met een Open Access Fonds
No full textOm Open Access onder de eigen medewerkers te promoten, beschikt TU Delft over een Open Access Fonds. Wat heeft dit fonds de afgelopen jaren opgeleverd? Anke Versteeg en Just de Leeuwe bespreken de resultaten en belichten en passant ook nieuwe ontwikkelingen. Engelse versie is zonder tabellen en niet gepubliceerdDelft University of Technolog
Author Correction: Near complete local extinction of iconic anemonefish and their anemone hosts following a heat stress event (npj Biodiversity, (2025), 4, 1, (35), 10.1038/s44185-025-00107-4)
No full text\ua9 The Author(s) 2025.Correction to: npj Biodiversityhttps://doi.org/10.1038/s44185-025-00107-4, article published online 12 September 2025 In the original version of this Article, co-authors Susana Carvalho, Melissa Versteeg & Theresa Rueger’s contributions were not provided. The Author Contributions statement has now been updated to correct this
Gene expression in chromosomal Ridge domains : influence on transcription, mRNA stability, codon usage, and evolution
No full textChromosomes are the long DNA molecules that carry the genetic code of our genes. Each gene encodes a protein, but also contains the information that controls the activity of that gene. In this thesis, we find that chromosomal domains with many active genes (so-called 'Ridges'), also control gene activity. Our results imply that Ridges facilitate the high activity of important genes. Ridges might thus provide an alternative mechanism for changes in gene activity during human evolution
Abstract A26: High frequency of Cytosine to Adenine mutations in neuroblastoma correlates with genomic aberrations in 8-Oxo-Guanine repair pathway
No full textAbstract
Background: Somatic mutations can be grouped into 96 tri-nucleotide patterns, termed mutational signatures. These signatures can provide insights into underlying processes that fuel the evolution of tumor cells, and may expose therapeutic intervention avenues. Here we investigated the mutational signature of 84 whole genome sequenced neuroblastoma cases.
Results: Mutational signature analysis revealed an extreme bias towards Cytosine to Adenine (CtoA) mutations in a majority of neuroblastoma tumors. This seems to be a unique feature of neuroblastoma. CtoA mutations are primarily found in high stage tumors and are therefore associated with a poor prognosis. Oxidative stress is known to be a source for such mutations, which can accumulate due to defects in the 8-Oxo-Guanine repair pathway genes OGG1, MUTYH and MTH1. We could show a strong correlation between CtoA mutations and chromosomal loss of MTH1, OGG1 and MUTYH. Besides copy number losses, sequencing also revealed a tumor with a homozygous mutation in OGG1 and this tumor showed a very strong bias towards CtoA mutations. Modified alkaline comet assays were performed for quantification of 8-Oxo-Guanine content present in the DNA of neuroblastoma cell lines. These comet assays showed that neuroblastoma cell lines with loss of either OGG1 or MUTYH, had higher 8-Oxo-Guanine content than cell lines without these losses. 8-Oxo-Guanine content is correlated with CtoA mutation frequency in short term cultured neuroblastoma organoids. Overexpression of OGG1 or MUTYH in neuroblastoma cell lines with losses of OGG1 or MUTYH respectively leads to rescue of the phenotype and a decrease in the amount of 8-Oxo-Guanine in the DNA. We are currently performing a compound screen to test the efficacy of 352 compounds functioning in the DNA damage repair in cell lines with and without MUTYH expression, and were testing compounds that further interfere in this specific branch of DNA damage repair including the newly developed MTH1 inhibitors.
Conclusion: We identified a subset of neuroblastoma tumors with a high CtoA mutation frequency, which correlates with losses of glycosylases involved in the repair of CtoA mutations. 8-Oxo-Guanine levels are elevated in cell lines with loss of OGG1 or MUTYH, which can be rescued by overexpression of OGG1 or MUTYH respectively.
Citation Format: Anne Hakkert, Marli E. Ebus, Rogier Versteeg, Caron N. Huib, Jan Koster, Jan J. Molenaar. High frequency of Cytosine to Adenine mutations in neuroblastoma correlates with genomic aberrations in 8-Oxo-Guanine repair pathway [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr A26.</jats:p
The role of OTX2 in medulloblastoma
No full textHet onderdrukken van het gen OTX2 lijkt een potentiële therapie voor medulloblastomen, een kwaadaardige hersentumor. Jens Bunt stelt dat OTX2 door binding aan het DNA de expressie van genen die nodig zijn voor celdeling aanzet, terwijl het indirect de differentiatie van cellen remt. Uit proeven met tumorcellen waarin OTX2 aan of uit gezet kan worden, blijkt dat OTX2 noodzakelijk is voor de vermeerdering van de medulloblastoomcellen. Het medulloblastoom is een kwaadaardige tumor van de kleine hersenen, meestal bij kinderen. Het gen OTX2, dat normaal alleen aanstaat tijdens de ontwikkeling, komt hoog tot expressie in de meerderheid van de tumoren
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