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    Intestinal epithelial barrier integrity investigated by label-free techniques in ulcerative colitis patients
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2023) Quansah, Elsie; Gardey, Elena; Ramoji, Anuradha; Meyer-Zedler, Tobias; Goehrig, Bianca; Heutelbeck, Astrid; Hoeppener, Stephanie; Schmitt, Michael; Waldner, Maximillian; Stallmach, Andreas; Popp, Jürgen
    The intestinal epithelial barrier, among other compartments such as the mucosal immune system, contributes to the maintenance of intestinal homeostasis. Therefore, any disturbance within the epithelial layer could lead to intestinal permeability and promote mucosal inflammation. Considering that disintegration of the intestinal epithelial barrier is a key element in the etiology of ulcerative colitis, further assessment of barrier integrity could contribute to a better understanding of the role of epithelial barrier defects in ulcerative colitis (UC), one major form of chronic inflammatory bowel disease. Herein, we employ fast, non-destructive, and label-free non-linear methods, namely coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and two-photon fluorescence lifetime imaging (2P-FLIM), to assess the morpho-chemical contributions leading to the dysfunction of the epithelial barrier. For the first time, the formation of epithelial barrier gaps was directly visualized, without sophisticated data analysis procedures, by the 3D analysis of the colonic mucosa from severely inflamed UC patients. The results were compared with histopathological and immunofluorescence images and validated using transmission electron microscopy (TEM) to indicate structural alterations of the apical junction complex as the underlying cause for the formation of the epithelial barrier gaps. Our findings suggest the potential advantage of non-linear multimodal imaging is to give precise, detailed, and direct visualization of the epithelial barrier in the gastrointestinal tract, which can be combined with a fiber probe for future endomicroscopy measurements during real-time in vivo imaging.
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    Time-scale synchronisation of oscillatory responses can lead to non-monotonous R-tipping
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2023) Swierczek-Jereczek, Jan; Robinson, Alexander; Blasco, Javier; Alvarez-Solas, Jorge; Montoya, Marisa
    Rate-induced tipping (R-tipping) describes the fact that, for multistable dynamic systems, an abrupt transition can take place not only because of the forcing magnitude, but also because of the forcing rate. In the present work, we demonstrate through the case study of a piecewise-linear oscillator (PLO), that increasing the rate of forcing can make the system tip in some cases but might also prevent it from tipping in others. This counterintuitive effect is further called non-monotonous R-tipping (NMRT) and has already been observed in recent studies. We show that, in the present case, the reason for NMRT is the peak synchronisation of oscillatory responses operating on different time scales. We further illustrate that NMRT can be observed even in the presence of additive white noise of intermediate amplitude. Finally, NMRT is also observed on a van-der-Pol oscillator with an unstable limit cycle, suggesting that this effect is not limited to systems with a discontinuous right-hand side such as the PLO. This insight might be highly valuable, as the current research on tipping elements is shifting from an equilibrium to a dynamic perspective while using models of increasing complexity, in which NMRT might be observed but hard to understand.