Publications by authors named "Christian F Nielsen"

During mitosis in eukaryotic cells, mechanical forces generated by the mitotic spindle pull the sister chromatids into the nascent daughter cells. How do mitotic chromosomes achieve the necessary mechanical stiffness and stability to maintain their integrity under these forces? Here we use optical tweezers to show that ions involved in physiological chromosome condensation are crucial for chromosomal stability, stiffness and viscous dissipation. We combine these experiments with high-salt histone depletion and theory to show that chromosomal elasticity originates from the chromatin fibre behaving as a flexible polymer, whereas energy dissipation can be explained by modelling chromatin loops as an entangled polymer solution.

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We demonstrate experimentally that the trident process e^{-}→e^{-}e^{+}e^{-} in a strong external field, with a spatial extension comparable to the effective radiation length, is well understood theoretically. The experiment, conducted at CERN, probes values for the strong field parameter χ up to 2.4.

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Scope: Ready-to-feed liquid infant formula is increasingly used for preterm infants when human milk is unavailable. These formulas are sterilized by ultra-high temperature treatment, but heating and storage may reduce bioactivity and increase formation of Maillard reaction products with potential negative consequences for immature newborns.

Methods And Results: Using preterm pigs as a model for sensitive newborn infants, the study tests the intestinal responses of feeding experimental liquid formula within 5 days.

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In preparation for mitotic cell division, the nuclear DNA of human cells is compacted into individualized, X-shaped chromosomes. This metamorphosis is driven mainly by the combined action of condensins and topoisomerase IIα (TOP2A), and has been observed using microscopy for over a century. Nevertheless, very little is known about the structural organization of a mitotic chromosome.

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Ready-to-feed liquid infant formulas (IF) were subjected to direct (D) or indirect (ID) ultra-high-temperature (UHT) treatment and then stored at 40 °C under aseptic conditions for 60-120 days simulating global transportation which accelerates the Maillard reaction. Low pasteurized and unstored IF (LP) was included as a control for the UHT treatments. Simulated infant digestion was conducted.

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Protein modifications in liquid infant formula (IF) have been widely studied, but distinguishing between heat- and storage-induced structural changes remains challenging. A generic liquid IF was subjected to direct or indirect UHT treatment and stored at 40 °C up to 180 days. Colour and pH were monitored and structural changes were characterised by dynamic light scattering, SDS-PAGE and centrifugal field-flow fractionation (FFF) coupled with multi-angle light scattering (MALS) and UV detectors to evaluate whether heat-induced differences would level out during storage.

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Topoisomerase IIα (TOP2A) is a core component of mitotic chromosomes and important for establishing mitotic chromosome condensation. The primary roles of TOP2A in mitosis have been difficult to decipher due to its multiple functions across the cell cycle. To more precisely understand the role of TOP2A in mitosis, we used the auxin-inducible degron (AID) system to rapidly degrade the protein at different stages of the human cell cycle.

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How spatial chromosome organization influences genome integrity is still poorly understood. Here, we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CCCTC-binding factor (CTCF) and cohesin-bound sites at the bases of chromatin loops, and their frequency positively correlates with transcriptional output and directionality.

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The reversible interconversion of formate (HCOO) and carbon dioxide (CO) is catalyzed by formate dehydrogenase (FDH, EC 1.17.1.

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Condensin, a highly conserved pentameric chromosome complex, is required for the correct organization and folding of the genome. Here, we highlight how to knock protein tags into endogenous loci to faithfully study the condensin complex in vertebrates and dissect its multiple functions. These include using the streptavidin binding peptide (SBP) to create the first genome-wide map of condensin and perform varied applications in proteomics and enzymology of the complex.

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Ultrafine anaphase bridges (UFBs) are thin DNA threads linking the separating sister chromatids in the anaphase of mitosis. UFBs are thought to form when topological DNA entanglements between two chromatids are not resolved prior to anaphase onset. In contrast to other markers of defective chromosome segregation, UFBs cannot be detected by direct staining of the DNA, but instead can be detected using immunofluorescence-based approaches.

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Transcription factor-based biosensors are used to identify producer strains, a critical bottleneck in cell factory engineering. Here, we address two challenges with this methodology: transplantation of heterologous transcriptional regulators into new hosts to generate functional biosensors and biosensing of the extracellular product concentration that accurately reflects the effective cell factory production capacity. We describe the effects of different translation initiation rates on the dynamic range of a p-coumaric acid biosensor based on the Bacillus subtilis transcriptional repressor PadR by varying its ribosomal binding site.

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A fundamental requirement in nature is for a cell to correctly package and divide its replicated genome. Condensin is a mechanical multisubunit complex critical to this process. Condensin uses ATP to power conformational changes in DNA to enable to correct DNA compaction, organization, and segregation of DNA from the simplest bacteria to humans.

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PICH is an SNF2-family DNA translocase that appears to play a role specifically in mitosis. Characterization of PICH in human cells led to the initial discovery of "ultra-fine DNA bridges" (UFBs) that connect the 2 segregating DNA masses in the anaphase of mitosis. These bridge structures, which arise from specific regions of the genome, are a normal feature of anaphase but had escaped detection previously because they do not stain with commonly used DNA dyes.

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PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193.

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Ultra-fine DNA bridges (UFBs) are a recently identified class of mitotic DNA structures that cannot be visualized using conventional DNA staining methods (e.g. using DAPI).

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Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive primary human breast cancer and function as effectors of ErbB2-induced invasion in vitro.

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