| 1. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Tsiantoulas, D., et al.
(författare)
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APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597, s. 92-96
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide(1). The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)(2) and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall(2). A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs(3), but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.
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| 3. |
- Chen, Xingchen, et al.
(författare)
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Potent, multi-target serine protease inhibition achieved by a simplified beta-sheet motif
- 2019
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Engagement of an extended beta-sheet is a common substrate/inhibitor interaction at the active site of serine proteases and is an important feature of Laskowski mechanism inhibitors that present a substrate-like loop to a target protease. This loop is cleaved but subsequently relegated forming a stable inhibitor/protease complex. Laskowski inhibitors are ubiquitous in nature and are used extensively in serine protease inhibitor design. However, most studies concentrate on introducing new sidechain interactions rather than the direct contributions of the substrate-like beta-sheet to enzyme inhibition. Here we report the crystal structure of an simplified beta-sheet inhibitory motif within the Sunflower Trypsin Inhibitor (SFTI) in complex with trypsin. We show that the intramolecular hydrogen bond network of this SFTI variant (SFTI-TCTR) engages the inhibitor sidechains that would normally interact with a target protease, giving mainchain interactions a more prominent role in complex formation. Despite having reduced sidechain interactions, this SFTI variant is remarkably potent and inhibits a diverse range of serine proteases. Crystal structural analysis and molecular modelling of SFTI-TCTR complexes again indicates an interface dominated by beta-sheet interactions, highlighting the importance of this motif and the adaptability of SFTI as a scaffold for inhibitor design.
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| 4. |
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| 5. |
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| 6. |
- Christoforo, M. Greyson, et al.
(författare)
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Transient response of organo-metal-halide solar cells analyzed by time-resolved current-voltage measurements
- 2015
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Ingår i: Photonics. - : MDPI AG. - 2304-6732. ; 2:4, s. 1101-1115
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Tidskriftsartikel (refereegranskat)abstract
- The determination of the power conversion efficiency of solar cells based on organo-metal-halides is subject to an ongoing debate. As solar cell devices may exhibit very slow transient response, current-voltage scans in different directions may not be congruent, which is an effect often referred to as hysteresis. We here discuss time-resolved current-voltage measurements as a means to evaluate appropriate delay times (voltage settling times) to be used in current-voltage measurements of solar cells. Furthermore, this method allows the analysis of transient current response to extract time constants that can be used to compare characteristic differences between devices of varying architecture types, selective contacts and changes in devices due to storage or degradation conditions.
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| 7. |
- Wik, G, et al.
(författare)
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Magnetic brain imaging of extinction processes in human classical conditioning
- 1997
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Ingår i: NEUROREPORT. - : RAPID SCIENCE PUBLISHERS. - 0959-4965. ; 8:7, s. 1789-1792
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Tidskriftsartikel (refereegranskat)abstract
- BY recording neuromagnetic events during aversive classical conditioning, we examined the extinction of a previously described conditioned response. Averaging over non-reinforced exposures to the conditioned stimulus revealed magnetic activity in the sec
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| 8. |
- Wik, G, et al.
(författare)
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Magnetic imaging in human classical conditioning
- 1996
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Ingår i: NEUROREPORT. - : RAPID SCIENCE PUBLISHERS. - 0959-4965. ; 7:3, s. 737-740
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Tidskriftsartikel (refereegranskat)abstract
- MAGNETOENCEPHALOGRAPHY (MEG) was recorded during aversive classical conditioning in an attempt to elucidate the temporal coding of primary somatosensory cortex (SI) activation previously found with positron emission tomography. Four healthy volunteers pa
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