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- Amzaleg, Y., et al.
(författare)
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Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells
- 2018
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 183, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17 beta-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At >= 10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting preosteoclast proliferation. That ral and las poorly mimic the locus-and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.
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- Kottwitz, Matthew, et al.
(författare)
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Local Structure and Electronic State of Atomically Dispersed Pt Supported on Nanosized CeO2
- 2019
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Ingår i: ACS Catalysis. - : AMER CHEMICAL SOC. - 2155-5435. ; 9:9, s. 8738-8748
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Tidskriftsartikel (refereegranskat)abstract
- Single atom catalysts (SACs) have shown high activity and selectivity in a growing number of chemical reactions. Many efforts aimed at unveiling the structure-property relationships underpinning these activities and developing synthesis methods for obtaining SACs with the desired structures are hindered by the paucity of experimental methods capable of probing the attributes of local structure, electronic properties, and interaction with support-features that comprise key descriptors of their activity. In this work, we describe a combination of experimental and theoretical approaches that include photon and electron spectroscopy, scattering, and imaging methods, linked by density functional theory calculations, for providing detailed and comprehensive information on the atomic structure and electronic properties of SACs. This characterization toolbox is demonstrated here using a model single atom Pt/CeO2 catalyst prepared via a sol-gel-based synthesis method. Isolated Pt atoms together with extra oxygen atoms passivate the (100) surface of nanosized ceria. A detailed picture of the local structure of Pt nearest environment emerges from this work involving the bonding of isolated Pt2+ ions at the hollow sites of perturbed (100) surface planes of the CeO2 support, as well as a substantial (and heretofore unrecognized) strain within the CeO2 lattice in the immediate vicinity of the Pt centers. The detailed information on structural attributes provided by our approach is the key for understanding and improving the properties of SACs.
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- Šaric, Andela, et al.
(författare)
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Physical determinants of the self-replication of protein fibrils
- 2016
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 12:9, s. 874-880
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Tidskriftsartikel (refereegranskat)abstract
- The ability of biological molecules to replicate themselves is the foundation of life, requiring a complex cellular machinery. However, a range of aberrant processes involve the self-replication of pathological protein structures without any additional assistance. One example is the autocatalytic generation of pathological protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders. Here, we use computer simulations to identify the necessary requirements for the self-replication of fibrillar assemblies of proteins. We establish that a key physical determinant for this process is the affinity of proteins for the surfaces of fibrils. We find that self-replication can take place only in a very narrow regime of inter-protein interactions, implying a high level of sensitivity to system parameters and experimental conditions. We then compare our theoretical predictions with kinetic and biosensor measurements of fibrils formed from the Aβ peptide associated with Alzheimer's disease. Our results show a quantitative connection between the kinetics of self-replication and the surface coverage of fibrils by monomeric proteins. These findings reveal the fundamental physical requirements for the formation of supra-molecular structures able to replicate themselves, and shed light on mechanisms in play in the proliferation of protein aggregates in nature.
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