| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
- Brevini, T, et al.
(författare)
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FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
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Tidskriftsartikel (refereegranskat)abstract
- Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
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| 4. |
- Huckvale, M., et al.
(författare)
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Opportunities for Computer-Aided Instruction in Phonetics and Speech Communication Provided by the Internet
- 1997
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Ingår i: 5th European Conference on Speech Communication and Technology, EUROSPEECH 1997. - : The International Speech Communication Association (ISCA). ; , s. 1919-1922
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Konferensbidrag (refereegranskat)abstract
- Spoken language engineering is starting to deliver technological products to the commercial market and has an important future role in supporting the multilingual structures of modern Europe. The field will be driven forward by basic science and applied research by experts drawn from a variety of backgrounds; among them: linguistics, psychology, computer science and electrical engineering. The wide range of expertise required in this discipline brings difficulties for our educational systems, but also challenges us to use our knowledge of technology and communication to improve the quality and effectiveness of teaching and learning. This paper investigates how resources currently available on the Internet could be exploited in the education of phonetics and speech communication. It discusses the technology, outlines the requirements for computer-aided learning in the field, gives a taxonomy of the available components with examples, and criticises the main weaknesses in the current provision.
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| 5. |
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| 6. |
- Örnebro, J, et al.
(författare)
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Adsorption of α-, β-, γ- and ω-Gliadins onto Hydrophobic Surfaces
- 1999
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Ingår i: Journal of Cereal Science. - : Elsevier BV. - 0733-5210. ; 77:5, s. 105-114
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Tidskriftsartikel (refereegranskat)abstract
- Adsorption onto hydrophobic surfaces of α-, β-, γ-, and ω-gliadins from the wheat variety Chinese Spring was studied by means of in situ ellipsometry. Most measurements were conducted in 0·01m phosphate buffer, pH 6·0, with the protein concentrations 1, 5 and 25 μg/mL. The adsorbed amount varied between 1·3 and 11·4 mg/m2, which is high considering the low protein concentrations. The concentration dependence was largest for the α-gliadins and lowest for the ω-gliadins. An intermediate concentration dependence was found for the β- and γ-gliadins, which also behaved similarly in all experiments. It was suggested that α-gliadins aggregated at the surface to a larger extent than the other gliadins when the protein concentration was 25 μg/mL. Further, it seemed as β- and γ-gliadins switched from a side-on orientation (major axis parallel to the surface) to an end-on orientation (major axis perpendicular to the surface) with increasing concentration, contrasting to the ω-gliadins that probably had side-on orientation at all concentrations. Sequential adsorption measurements indicated that α-, β-, and γ-gliadins blocked adsorption of ω-gliadins, but could replace ω-gliadins in a previously formed layer.
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| 7. |
- Örnebro, Jörgen, et al.
(författare)
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The behaviour of the high molecular-weight glutenin subunit 1Dx5, the 58 kDa central repetitive domain and a-gliadins at the air-aqueous interface.
- 2003
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Ingår i: Journal of Cereal Science. - 0733-5210. ; 38:2, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- The surface pressure–molecular area (–A) relationship for spread layers of the high molecular-weight glutenin subunit 1Dx5, a 58 kDa peptide derived from the central repetitive domain of the subunit, and an -gliadin fraction was measured by means of a surface film balance (Langmuir trough). The aqueous phase was a 10 mM acetate buffer, pH 4.0, either with or without 100 mM NaCl. Subunit 1Dx5 generated much higher surface pressures than the 58 kDa peptide, whereas the -gliadin fraction generally gave higher surface pressures than subunit 1Dx5. Furthermore, subunit 1Dx5, but not the 58 kDa peptide or the -gliadin fraction, formed a highly cohesive film. The differences in the interfacial behaviour of subunit 1Dx5 and the 58 kDa peptide were ascribed to significant hydrophobic interactions for the subunit. The reversibility of a compression–expansion cycle was generally greater for the second cycle than for the first. For subunit 1Dx5 and the -gliadins, but not the 58 kDa peptide, the reversibility was increased when NaCl was present in the aqueous phase.
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