| 1. |
- Diaz, Oscar E., et al.
(author)
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Perfluorooctanesulfonic acid modulates barrier function and systemic T-cell homeostasis during intestinal inflammation
- 2021
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In: DMM Disease Models and Mechanisms. - : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 14:12, s. 1-11
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Journal article (peer-reviewed)abstract
- The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are poorly understood. Here, to overcome the lack of in vivo models suitable for screening of environmental factors, we used zebrafish reporters of intestinal inflammation. Using zebrafish, we interrogated the immunomodulatory effects of polyfluoroalkyl substances, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in the TNBS-induced colitis mouse model. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into the circulation. This was associated with a neutrophil-dependent expansion of systemic CD4+ T cells. Thus, our results indicate that PFOS worsens inflammation-induced intestinal damage with disruption of T-cell homeostasis beyond the gut and provides a novel in vivo toolbox to screen for pollutants affecting intestinal homeostasis.
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| 2. |
- Frede, Annika, et al.
(author)
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B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing
- 2022
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In: Immunity. - : Elsevier BV. - 1074-7613 .- 1097-4180. ; 55:12, s. 2336-
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Journal article (peer-reviewed)abstract
- Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) re-vealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue re-modeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for orga-noid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.
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| 3. |
- Liu, Jinyang, et al.
(author)
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Fabrication of Graphene Nanomesh and Improved Chemical Enhancement for Raman Spectroscopy
- 2012
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In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 116:29, s. 15741-15746
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Journal article (peer-reviewed)abstract
- We propose a new approach to fabricate the graphene nanomesh through the local catalytic hydrogenation of carbon by Cu nanoparticles. It allows to tune the size and density of the holes in the nanomesh as well as the total edge length of the holes through the control of the thickness of the Cu film. The upshift of both G and 2D peaks in Raman spectra of the graphene nanomeshes indicates that the nanomesh is spontaneously p-type doped. Moreover, the split of G peak reveals that the doping is localized near the edge region of the hole in the nanomesh. Importantly, the nanomesh shows improved chemical enhancement for Raman spectra of absorbed RhB molecules as compared to the graphene. The edges in the nanomesh can enhance Raman spectroscopy via increasing both the local charge transfer and the ability to absorb RhB molecules. The results show that the graphene nanomesh has a great potential for the rapid and sensitive detection for the environmental monitoring and food security.
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| 4. |
- Parigi, Sara M., et al.
(author)
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The spatial transcriptomic landscape of the healing mouse intestine following damage
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- The colon is comprised of specialized cells that interact with each other to function, however, the molecular regionalization of the colon is incompletely understood. Here, the authors use spatial transcriptomics to generate a publicly available resource defining the transcriptomic regionalization of the colon during steady state and mucosal healing. The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we mapped transcriptomics modules associated with human diseases demonstrating the translational potential of our dataset. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.
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