| 61. |
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| 62. |
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| 63. |
- Berger, Gilles, et al.
(författare)
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Insights into the structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives
- 2015
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 20:5, s. 841-853
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Tidskriftsartikel (refereegranskat)abstract
- The structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives are studied, including interactions with telomeric- and genomic-like DNA sequences, the pKa of their diaqua species, structural properties obtained from DFT calculations and resonant X-ray emission spectroscopy. The binding modes of the compounds to telomeric sequences were elucidated, showing no major differences with conventional cis-platinum(II) complexes like cisplatin, supporting that the cis-square planar geometry governs the binding of small Pt(II) complexes to G4 structures. Double-stranded DNA platination kinetics and acid-base constants of the diaqua species of the compounds were measured and compared, highlighting a strong steric dependence of the DNA-binding kinetics, but independent to stereoisomerism. Structural features of the compounds are discussed on the basis of dispersion-corrected DFT, showing that the most active series presents conformers for which the platinum atom is well devoid of steric hindrance. If reactivity indices derived from conceptual DFT do not show evidences for different reactivity between the compounds, RXES experiments provide new insight into the availability of platinum orbitals for binding to nucleophiles.
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| 64. |
- Berger, Gilles, et al.
(författare)
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Reduction Mechanisms of Anticancer Osmium(VI) Complexes Revealed by Atomic Telemetry and Theoretical Calculations
- 2021
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 60:9, s. 6663-6671
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Tidskriftsartikel (refereegranskat)abstract
- Resonant X-ray emission spectroscopy (RXES) has developed in the past decade as a powerful tool to probe the chemical state of a metal center and in situ study chemical reactions. We have used it to monitor spectral changes associated with the reduction of osmium(VI) nitrido complexes to the osmium(III) ammine state by the biologically relevant reducing agent, glutathione. RXES difference maps are consistent with the proposed DFT mechanism and the formation of two stable osmium(IV) intermediates, thereby supporting the overall pathway for the reduction of these high-valent anticancer metal complexes for which reduction by thiols within cells may be essential to the antiproliferative activity.
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| 65. |
- Laplante, Mathieu, et al.
(författare)
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Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat
- 2009
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - Bethesda, Md. : American Physiological Society. - 0363-6119 .- 1522-1490. ; 296:1, s. R57-R66
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein.
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| 66. |
- Martin-Torres, Javier, et al.
(författare)
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Transient liquid water and water activity at Gale crater on Mars
- 2015
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 8:5, s. 357-361
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Tidskriftsartikel (refereegranskat)abstract
- Water is a requirement for life as we know it1. Indirect evidence of transient liquid water has been observed from orbiter on equatorial Mars2, in contrast with expectations from large-scale climate models. The presence of perchlorate salts, which have been detected at Gale crater on equatorial Mars by the Curiosity rover3, 4, lowers the freezing temperature of water5. Moreover, perchlorates can form stable hydrated compounds and liquid solutions by absorbing atmospheric water vapour through deliquescence6, 7. Here we analyse relative humidity, air temperature and ground temperature data from the Curiosity rover at Gale crater and find that the observations support the formation of night-time transient liquid brines in the uppermost 5 cm of the subsurface that then evaporate after sunrise. We also find that changes in the hydration state of salts within the uppermost 15 cm of the subsurface, as measured by Curiosity, are consistent with an active exchange of water at the atmosphere–soil interface. However, the water activity and temperature are probably too low to support terrestrial organisms8. Perchlorates are widespread on the surface of Mars9 and we expect that liquid brines are abundant beyond equatorial regions where atmospheric humidity is higher and temperatures are lower.
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| 67. |
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| 68. |
- Myszkowska, Dorota, et al.
(författare)
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Co-exposure to highly allergenic airborne pollen and fungal spores in Europe
- 2023
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Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 905, s. 167285-167285
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Tidskriftsartikel (refereegranskat)abstract
- The study is aimed at determining the potential spatiotemporal risk of the co-occurrence of airborne pollen and fungal spores high concentrations in different bio-climatic zones in Europe. Birch, grass, mugwort, ragweed, olive pollen and Alternaria and Cladosporium fungal spores were investigated at 16 sites in Europe, in 2005–2019. In Central and northern Europe, pollen and fungal spore seasons mainly overlap in June and July, while in South Europe, the highest pollen concentrations occur frequently outside of the spore seasons. In the coldest climate, no allergy thresholds were exceeded simultaneously by two spore or pollen taxa, while in the warmest climate most of the days with at least two pollen taxa exceeding threshold values were observed. The annual air temperature amplitude seems to be the main bioclimatic factor influencing the accumulation of days in which Alternaria and Cladosporium spores simultaneously exceed allergy thresholds. The phenomenon of co-occurrence of airborne allergen concentrations gets increasingly common in Europe and is proposed to be present on other continents, especially in temperate climate.
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| 69. |
- Sa, Jacinto, et al.
(författare)
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Resonant X-ray emission spectroscopy of platinum(II) anticancer complexes
- 2016
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Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 141:4, s. 1226-1232
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Tidskriftsartikel (refereegranskat)abstract
- Platinum-based drugs are commonly used in cancer treatment. The biological activity of a metallodrug is obviously closely related to its chemical and stereochemical characteristics. An overlooked aspect is the effect of the ligand to the electronic structure of the metal atom (coordinated atom). We report herein a Resonant X-ray Emission Spectroscopy (RXES) study on the chemical speciation of chiral platinum complexes in which diastereomers are distinguished on the basis of their metal electronic configuration. This demonstrates RXES high chemical speciation capabilities, a necessary property to further investigate the reactivity of the Pt atom towards nucleophiles or bionucleophiles, and an important complement the previously reported RXES abilities, namely that it can be employed for in situ studies at physiological concentrations.
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| 70. |
- Sá, Jacinto, et al.
(författare)
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The use of Resonant X-ray Emission Spectroscopy (RXES) for the electronic analysis of metal complexes and their interactions with biomolecules.
- 2015
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1740-6749. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- This review presents a new application of Resonant X-ray Emission Spectroscopy (RXES) to study the mechanism of action of metal containing anticancer derivatives and in particular platinum in situ and in vivo. The technique is an example of a photon-in photon-out X-ray spectroscopic approach, which enables chemical speciation of drugs to be determined and therefore to derive action mechanisms, and to determine drug binding rates under physiological conditions and therapeutic concentrations. This is made feasible due to the atomic specificity and high penetration depth of RXES. The review presents examples of the three main types of information that can be obtained by RXES and establishes an experimental protocol to perfect the measurements within cells.
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