| 1. |
- Bovay, Esther, et al.
(author)
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Multiple roles of lymphatic vessels in peripheral lymph node development
- 2018
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 215:11, s. 2760-2777
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Journal article (peer-reviewed)abstract
- The mammalian lymphatic system consists of strategically located lymph nodes (LNs) embedded into a lymphatic vascular network. Mechanisms underlying development of this highly organized system are not fully understood. Using highresolution imaging, we show that lymphoid tissue inducer (LTi) cells initially transmigrate from veins at LN development sites using gaps in venous mural coverage. This process is independent of lymphatic vasculature, but lymphatic vessels are indispensable for the transport of LTi cells that egress from blood capillaries elsewhere and serve as an essential LN expansion reservoir. At later stages, lymphatic collecting vessels ensure efficient LTi cell transport and formation of the LN capsule and subcapsular sinus. Perinodal lymphatics also promote local interstitial flow, which cooperates with lymphotoxin-beta signaling to amplify stromal CXCL13 production and thereby promote LTi cell retention. Our data unify previous models of LN development by showing that lymphatics intervene at multiple points to assist LN expansion and identify a new role for mechanical forces in LN development.
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| 2. |
- Dendooven, Amélie, et al.
(author)
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Coding practice in national and regional kidney biopsy registries
- 2021
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In: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Kidney biopsy registries all over the world benefit research, teaching and health policy. Comparison, aggregation and exchange of data is however greatly dependent on how registration and coding of kidney biopsy diagnoses are performed. This paper gives an overview over kidney biopsy registries, explores how these registries code kidney disease and identifies needs for improvement of coding practice. Methods: A literature search was undertaken to identify biopsy registries for medical kidney diseases. These data were supplemented with information from personal contacts and from registry websites. A questionnaire was sent to all identified registries, investigating age of registries, scope, method of coding, possible mapping to international terminologies as well as self-reported problems and suggestions for improvement. Results: Sixteen regional or national kidney biopsy registries were identified, of which 11 were older than 10 years. Most registries were located either in Europe (10/16) or in Asia (4/16). Registries most often use a proprietary coding system (12/16). Only a few of these coding systems were mapped to SNOMED CT (1), older SNOMED versions (2) or ERA-EDTA PRD (3). Lack of maintenance and updates of the coding system was the most commonly reported problem. Conclusions: There were large gaps in the global coverage of kidney biopsy registries. Limited use of international coding systems among existing registries hampers interoperability and exchange of data. The study underlines that the use of a common and uniform coding system is necessary to fully realize the potential of kidney biopsy registries.
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| 3. |
- Keller, Rebecca, et al.
(author)
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The Escherichia coli envelope stress sensor CpxA can sense changes in lipid bilayer properties
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Other publication (other academic/artistic)abstract
- Membrane proteins are evolutionarily integrated with their lipid bilayer environment, but it is only marginally understood how they sense and adapt to changes in lipid composition. Here we use an in vitro reconstitution system to demonstrate that the activity of envelope stress sensor CpxA of Escherichia coli is modulated by lipid bilayer properties. By changing the lipid composition of the vesicles, and using lipid-engineered E. coli strains we show that CpxA activity is regulated by means of different properties of the bilayer: (i) anionic surface charge (ii) membrane curvature (iii) thus lateral bilayer stress but also (iv) membrane bilayer thickness. We conclude that the CpxA could sense changes in the lipid bilayer properties.
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| 4. |
- Keller, Rebecca, et al.
(author)
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The Escherichia coli envelope stress sensor CpxA can sense changes in lipid bilayer properties
- 2015
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In: ACS Biochemistry. ; 54:23, s. 3670-3676
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Journal article (peer-reviewed)abstract
- The Cpx stress response system is induced by various environmental and cellular stimuli. It is also activated in Escherichia coli strains lacking the major phospholipid, phosphatidylethanolamine (PE). However, it is not known whether CpxA directly senses changes in the lipid bilayer or the presence of misfolded proteins due to the lack of PE in their membranes. To address this question, we used an in vitro reconstitution system and vesicles with different lipid compositions to track modulations in the activity of CpxA in different lipid bilayers. Moreover, the Cpx response was validated in vivo by monitoring expression of a PcpxP-gfp reporter in lipid-engineered strains of E. coli. Our combined data indicate that CpxA responds specifically to different lipid compositions.
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| 5. |
- Keller, Rebecca, et al.
(author)
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The Escherichia coli Envelope Stress Sensor CpxA Responds to Changes in Lipid Bilayer Properties
- 2015
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In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 54:23, s. 3670-3676
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Journal article (peer-reviewed)abstract
- The Cpx stress response system is induced by various environmental and cellular stimuli. It is also activated in Escherichia coli strains lacking the major phospholipid, phosphatidylethanolamine (PE). However, it is not known whether CpxA directly senses changes in the lipid bilayer or the presence of misfolded proteins due to the lack of PE in their membranes. To address this question, we used an in vitro reconstitution system and vesicles with different lipid compositions to track modulations in the activity of CpxA in different lipid bilayers. Moreover, the Cpx response was validated in vivo by monitoring expression of a PcpxP-gfp reporter in lipid-engineered strains of E. coli. Our combined data indicate that CpxA responds specifically to different lipid compositions.
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| 6. |
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| 7. |
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| 8. |
- Lyons, Oliver, et al.
(author)
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Human venous valve disease caused by mutations in FOXC2 and GJC2
- 2017
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:8, s. 2437-2452
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Journal article (peer-reviewed)abstract
- Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1(hi) endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1(hi) endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events. Genetic deletion of Gjc2, Gja4, or Gja1 also disrupted early VV Prox1(hi) endothelial organization at postnatal day 0, and this likely underlies the VV defects seen in patients with GJC2 mutations. Knockout of Gja4 or Gjc2 resulted in reduced proliferation of Prox1(hi) valve-forming cells. At later stages of blood flow, Foxc2 and calcineurin-Nfat signaling are each required for growth of the valve leaflets, whereas Foxc2 is not required for VV maintenance.
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| 9. |
- Sabine, Amelie, et al.
(author)
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FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature
- 2015
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:10, s. 3861-3877
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Journal article (peer-reviewed)abstract
- Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.
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| 10. |
- Sabine, Amélie, et al.
(author)
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Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation.
- 2012
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In: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 22:2
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Journal article (peer-reviewed)abstract
- Lymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction.
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