We examine how channel confinement affects the equilibrium properties of topologically linked ring polymers and, by contrast, of equivalent unlinked rings, too. By performing extensive simulations of semiflexible rings of different chain length, N, and channel diameter, D, we discover three notable properties purely due to linking. First, upon entering the weak confinement regime, the length of the physically linked portion, The, becomes independent of chain length. Next, even when confinement is strong enough to pull apart and segregate unlinked rings, stays much larger than in the highly stretched limit. Finally, at fixed N, varies approximately as D 0.5, and we provide a simple scaling argument for this power–law behavior. These properties, which may hold for different link topologies, can be tested by current experimental setups on DNA rings confined in microchannels. Moreover, they could be relevant for the efficient in vivo unlinking of newly replicated bacterial chromosomes.
We study catenated ring polymers confined inside channels and slits with Langevin dynamics simulations and address how the contour position and size of the interlocked or physically linked region evolve with time. We show that the catenation constraints generate a drag, or topological friction, that couples the contour motion of the interlocked regions. Notably, the coupling strength decreases as the interlocking is made tighter, but also shorter, by confinement. Though the coupling strength differs for channel and slit confinement, the data outline a single universal curve when plotted against the size of the linked region. Finally, we study how the relaxation kinetics changes after one of the rings is cut open and conclude that considering interlocked circular polymers is key for isolating the manifestations of topological friction. The results ought to be relevant for linked biomolecules in experimental or biological confining conditions.
Coeliac disease (CD) is an immune-mediated enteropathy triggered by gluten ingestion. At CD diagnosis, gender differences have been previously reported, but data regarding follow-up are scant. We investigated gender differences in CD adult patients both at the time of diagnosis and at follow-up after the start of the gluten-free diet (GFD). This is a longitudinal cohort study on adult CD patients diagnosed between 2008 and 2019. Clinical, biochemical, and histological data were assessed and compared between males and females. At diagnosis, female gender was significantly associated with signs of malabsorption (OR 3.39; 95% CI: 1.4–7.9), longer duration of symptoms and/or signs before the diagnosis (OR 3.39; 95% CI: 1.5–7.5), heartburn (OR 2.99; 95% CI: 1.1–8.0), dyspepsia (OR 2.70; 95% CI: 1.1–6.5), nausea/vomit (OR 3.53; 95% CI: 1.1–10.9), and constipation (OR 4.84; 95% CI: 1.2–19.6) and less frequently associated to higher body mass index (OR 0.88; 95% CI: 0.8–0.9) and osteopenia/osteoporosis (OR 0.30; 95% CI: 0.1–0.7) compared to male patients. After 12–30 months, females presented lower median BMI, performed less frequently histological control, and had more frequently anaemia and hypoferritinaemia compared to males. No significant differences concerning the presence of gastrointestinal symptoms, adherence to GFD, and Marsh score were found. Gender differences found at CD diagnosis mostly disappear at the follow-up, showing that these differences can be solved over time.
Chromatin organization is nowadays accessible from population and single cell Hi-C data in the form of large contact matrices. Yet reconstructing the three-dimensional chromatin structure remains challenging and relies on polymer models and numerical simulations to account for these Hi-C data. Here we propose a novel optimization algorithm to identify cross-linker ensemble reproducing the experimental contact matrix. Furthermore, based on the polymer configurations extracted from the optimization procedure, we identify high changing curvature (HCC) regions in the chromatin, detected both in population and in single cell Hi-C, that we also compare to Topological Associated Domains (TADs). We report here that the HCC regions correlate with gene expression and CTCF high density distribution. Interestingly, the HCC region locations are heterogeneous across one cell repeats, revealing cell-to-cell variability. To conclude, HCC regions appear both in single and population Hi-C polymer reconstruction and can provide a possible unit for gene regulation.
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