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Royal Netherlands Academy of Arts and S... Publications | LitMetric

27 results match your criteria: "Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht[Affiliation]"

Article Synopsis
  • The study investigates whether primary tumor cells can metastasize randomly or require specialized traits by examining 26 colorectal cancer patients with peritoneal metastases.
  • Using a detailed sampling method, the research finds that peritoneal metastases are more heterogeneous than liver metastases and influenced by factors like chemotherapy.
  • The origins of peritoneal metastases are often at the deep-invading edge of primary tumors and generally do not share a common subclonal origin with distant metastases, indicating different selective pressures impacting cancer cells during metastasis.
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The transmission of a complete set of chromosomes to daughter cells during cell division is vital for development and tissue homeostasis. The spindle assembly checkpoint (SAC) ensures correct segregation by informing the cell cycle machinery of potential errors in the interactions of chromosomes with spindle microtubules prior to anaphase. To do so, the SAC monitors microtubule engagement by specialized structures known as kinetochores and integrates local mechanical and chemical cues such that it can signal in a sensitive, responsive and robust manner.

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Loss of LGR4/GPR48 causes severe neonatal salt wasting due to disrupted WNT signaling altering adrenal zonation.

J Clin Invest

February 2023

Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, and.

Disorders of isolated mineralocorticoid deficiency, which cause potentially life-threatening salt-wasting crisis early in life, have been associated with gene variants of aldosterone biosynthesis or resistance; however, in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone-producing adrenal zona glomerulosa (zG). Herein, we describe a highly consanguineous family with multiple perinatal deaths and infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness.

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Aneuploidy is a hallmark of cancer and a major cause of miscarriages in humans. It is caused by chromosome segregation errors during cell divisions. Evidence is mounting that the probability of specific chromosomes undergoing a segregation error is non-random.

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Chromosome segregation errors during cell divisions generate aneuploidies and micronuclei, which can undergo extensive chromosomal rearrangements such as chromothripsis. Selective pressures then shape distinct aneuploidy and rearrangement patterns-for example, in cancer-but it is unknown whether initial biases in segregation errors and micronucleation exist for particular chromosomes. Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, we show that chromosomes have different segregation error frequencies that result in non-random aneuploidy landscapes.

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The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of three-dimensional (3D) organoids from adult thyroid tissue representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCOs) harbor the complete machinery of hormone production as visualized by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarized epithelial cells that surround a central lumen.

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Genomic analysis finds no evidence of canonical eukaryotic DNA processing complexes in a free-living protist.

Nat Commun

October 2021

Institute for Comparative Genomics (ICG), Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, B3H 4R2, Canada.

Cells replicate and segregate their DNA with precision. Previous studies showed that these regulated cell-cycle processes were present in the last eukaryotic common ancestor and that their core molecular parts are conserved across eukaryotes. However, some metamonad parasites have secondarily lost components of the DNA processing and segregation apparatuses.

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Aneuploidy is the leading cause of miscarriage and congenital birth defects, and a hallmark of cancer. Despite this strong association with human disease, the genetic causes of aneuploidy remain largely unknown. Through exome sequencing of patients with constitutional mosaic aneuploidy, we identified biallelic truncating mutations in CENATAC (CCDC84).

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Single-cell derived tumor organoids display diversity in HLA class I peptide presentation.

Nat Commun

October 2020

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.

Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system.

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The tremendous diversity in eukaryotic life forms can ultimately be traced back to evolutionary modifications at the level of molecular networks. Deep understanding of these modifications will not only explain cellular diversity, but will also uncover different ways to execute similar processes and expose the evolutionary 'rules' that shape the molecular networks. Here, we review the evolutionary dynamics of the spindle assembly checkpoint (SAC), a signaling network that guards fidelity of chromosome segregation.

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Much of our knowledge regarding the interactions between epithelial tissues and the immune system has been gathered from animal models and co-cultures with cell lines. However, unique features of human cells cannot be modelled in mice, and cell lines are often transformed or genetically immortalized. Organoid technology has emerged as a powerful tool to maintain epithelial cells in a near-native state.

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Cycling intestinal Lgr5 stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells provide multiple secreted (e.g.

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There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy.

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Article Synopsis
  • Mammalian epidermal stem cells help keep the skin healthy and regenerate it throughout adult life, but effective long-term culture systems have been lacking.
  • A new epidermal organoid culture system allows for the stable expansion of these stem cells without the need for feeder cells or serum, mimicking the natural structure of mouse skin.
  • This innovative system utilizes a specific combination of signaling factors to maintain the organization of the skin cells and offers a valuable method for studying skin health and disease in the lab.
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Background: Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high.

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Article Synopsis
  • Researchers studied heart stem cells to see if they help heal heart tissue after damage.
  • They found that heart muscle cells only grow a lot when a baby is growing, and other types of heart cells help repair damage instead.
  • They didn’t find any resting stem cells or proof that other cell types can turn into heart muscle cells after an injury.
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Periodontitis is a highly prevalent chronic inflammatory disease of the periodontium, leading ultimately to tooth loss. In order to characterize the gene expression of periodontitis-affected gingival tissue, we have here simultaneously quantified and localized gene expression in periodontal tissue using spatial transcriptomics, combining RNA sequencing with histological analysis. Our analyses revealed distinct clusters of gene expression, which were identified to correspond to epithelium, inflamed areas of connective tissue, and non-inflamed areas of connective tissue.

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The enteric nervous system (ENS) is essential for digestive function and gut homeostasis. Here we show that the amorphous neuroglia networks of the mouse ENS are composed of overlapping clonal units founded by postmigratory neural crest-derived progenitors. The spatial configuration of ENS clones depends on proliferation-driven local interactions of ENS progenitors with lineally unrelated neuroectodermal cells, the ordered colonization of the serosa-mucosa axis by clonal descendants, and gut expansion.

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Sox7 controls arterial specification in conjunction with hey2 and efnb2 function.

Development

May 2015

Hubrecht Institute - Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Münster, 48149 Münster, Germany Institute for Cardiovascular Organogenesis and Regeneration, Faculty of Medicine, Westfälische Wilhelms-Universität Münster (WWU), Mendelstrasse 7, 48149 Münster, Germany

SoxF family members have been linked to arterio-venous specification events and human pathological conditions, but in contrast to Sox17 and Sox18, a detailed in vivo analysis of a Sox7 mutant model is still lacking. In this study we generated zebrafish sox7 mutants to understand the role of Sox7 during vascular development. By in vivo imaging of transgenic zebrafish lines we show that sox7 mutants display a short circulatory loop around the heart as a result of aberrant connections between the lateral dorsal aorta (LDA) and either the venous primary head sinus (PHS) or the common cardinal vein (CCV).

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Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization of the intermediate filament network.

J Cell Sci

October 2014

Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1090 GE Amsterdam, The Netherlands Department of Translational Neuroscience, Brain Center Rudolf Magus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CX, Utrecht, The Netherlands

Glial fibrillary acidic protein (GFAP) is the main intermediate filament in astrocytes and is regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation also controls GFAP expression in mature astrocytes. Inhibition of histone deacetylases (HDACs) with trichostatin A or sodium butyrate reduced GFAP expression in primary human astrocytes and astrocytoma cells.

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Structures of Wnt-antagonist ZNRF3 and its complex with R-spondin 1 and implications for signaling.

PLoS One

March 2015

Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

Zinc RING finger 3 (ZNRF3) and its homolog RING finger 43 (RNF43) antagonize Wnt signaling in adult stem cells by ubiquitinating Frizzled receptors (FZD), which leads to endocytosis of the Wnt receptor. Conversely, binding of ZNRF3/RNF43 to LGR4-6 - R-spondin blocks Frizzled ubiquitination and enhances Wnt signaling. Here, we present crystal structures of the ZNRF3 ectodomain and its complex with R-spondin 1 (RSPO1).

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In C. elegans and Drosophila, retromer mediated retrograde transport of Wntless (Wls) from endosomes to the trans-Golgi network (TGN) is required for Wnt secretion. When this retrograde transport pathway is blocked, Wls is missorted to lysosomes and degraded, resulting in reduced Wnt secretion and various Wnt related phenotypes.

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Bone mineralization is an essential step during the embryonic development of vertebrates, and bone serves vital functions in human physiology. To systematically identify unique gene functions essential for osteogenesis, we performed a forward genetic screen in zebrafish and isolated a mutant, no bone (nob), that does not form any mineralized bone. Positional cloning of nob identified the causative gene to encode ectonucleoside triphosphate/diphosphohydrolase 5 (entpd5); analysis of its expression pattern demonstrates that entpd5 is specifically expressed in osteoblasts.

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Background: Mutagenesis screens in the mouse have been proven useful for the identification of novel gene functions and generation of interesting mutant alleles. Here we describe a phenotype-based screen for recessive mutations affecting embryonic development.

Methodology/principal Findings: Mice were mutagenized with N-ethyl-N-nitrosourea (ENU) and following incrossing the offspring, embryos were analyzed at embryonic day 10.

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