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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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- Novak, R., et al.
(författare)
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Robotic fluidic coupling and interrogation of multiple vascularized organ chips
- 2020
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Ingår i: Nature Biomedical Engineering. - : Nature Research. - 2157-846X.
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Tidskriftsartikel (refereegranskat)abstract
- Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.
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7. |
- Zheng, Ju, et al.
(författare)
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Role of the ribosomal quality control machinery in nucleocytoplasmic translocation of polyQ-expanded huntingtin exon-1
- 2017
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 493:1, s. 708-717
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Tidskriftsartikel (refereegranskat)abstract
- The subcellular localization of polyQ-expanded huntingtin exon1 (Httex1) modulates polyQ toxicity in models of Huntington's disease. Using genome-wide screens in a yeast model system, we report that the ribosome quality control (RQC) machinery, recently implicated in neurodegeneration, is a key determinant for the nucleocytoplasmic distribution of Httex1-103Q, Deletion of the RQC genes, LTN1 or RQC1, caused the accumulation of Httex1-103Q in the nucleus through a process that required the CAT-tail tagging activity of Rqc2 and transport via the nuclear pore complex. We provide evidence that nuclear accumulation of Httex1-103Q enhances its cytotoxicity, suggesting that the RQC machinery plays an important role in protecting cells against the adverse effects of polyQ expansion proteins. (C) 2017 The Authors. Published by Elsevier Inc.
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