| 1. |
- Eriksson, Leif A., 1964-, et al.
(författare)
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Tetrazole derivatives as cytochrome p450 inhibitors
- 2019
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Patent (populärvet., debatt m.m.)abstract
- According to the invention there is provided a compound of formula I, wherein R1 and R2 have meanings given in the description, which compounds are useful in the treatment of skin disorders and other diseases.
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| 2. |
- Hyvonen, R., et al.
(författare)
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The likely impact of elevated [CO2], nitrogen deposition, increased temperature and management on carbon sequestration in temperate and boreal forest ecosystems: a literature review
- 2007
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Ingår i: New Phytologist. - Cambridge : Wiley. - 0028-646X .- 1469-8137. ; 173:3, s. 463-480
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Forskningsöversikt (refereegranskat)abstract
- Temperate and boreal forest ecosystems contain a large part of the carbon stored on land, in the form of both biomass and soil organic matter. Increasing atmospheric [CO2], increasing temperature, elevated nitrogen deposition and intensified management will change this C store. Well documented single-factor responses of net primary production are: higher photosynthetic rate (the main [CO2] response); increasing length of growing season (the main temperature response); and higher leaf-area index (the main N deposition and partly [CO2] response). Soil organic matter will increase with increasing litter input, although priming may decrease the soil C stock initially, but litter quality effects should be minimal (response to [CO2], N deposition, and temperature); will decrease because of increasing temperature; and will increase because of retardation of decomposition with N deposition, although the rate of decomposition of high-quality litter can be increased and that of low-quality litter decreased. Single-factor responses can be misleading because of interactions between factors, in particular those between N and other factors, and indirect effects such as increased N availability from temperature-induced decomposition. In the long term the strength of feedbacks, for example the increasing demand for N from increased growth, will dominate over short-term responses to single factors. However, management has considerable potential for controlling the C store.
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| 3. |
- Napolitano, C., et al.
(författare)
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Synthesis, kinase activity and molecular modeling of a resorcylic acid lactone incorporating an amide and a trans-enone in the macrocycle
- 2012
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 68:27-28, s. 5533-5540
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Tidskriftsartikel (refereegranskat)abstract
- Details for the synthesis of a resorcylic acid lactone (RAL) incorporating a trans-enone and an amide in the macrocyclic ring are provided herein. The sequence included the assembly of three fragments by esterification, olefination, and lactamization. The RAL with the lactam was less potent as an inhibitor of kinases than other RALs investigated. The biological results were rationalized by docking and molecular dynamics simulations of the lactam bound to human ERK2 and comparison with hypothemycin. (c) 2012 Elsevier Ltd. All rights reserved.
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| 4. |
- Karlsson, Therese, 1987, et al.
(författare)
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Hyperspectral imaging and data analysis for detecting and determining plastic contamination in seawater filtrates
- 2016
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Ingår i: Journal of Near Infrared Spectroscopy. - Chichester, England : SAGE Publications. - 0967-0335 .- 1751-6552. ; 24:2, s. 141-149
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Tidskriftsartikel (refereegranskat)abstract
- One possible way of monitoring plastic particles in sea water is by imaging spectroscopic measurements on filtrates. The idea is that filters from seawater sampling can be imaged in many wavelengths and that a multivariate data analysis can give information on (1) spatial location of plastic material on the filter and (2) composition of the plastic materials. This paper reports on simulated samples with spiked reference plastic particles, and real seawater filtrates containing microplastic pollutants. These real samples were previously identified through visual examination in a microscope. The samples were imaged using three different imaging systems. The different wavelength ranges were 375–970nm, 960–1662nm and 1000–2500nm. Data files from all three imaging systems were analysed by hyperspectral image analysis. The method using the wavelength span 1000–2500nm was shown to be the most applicable to this specific type of samples and gave a 100% particle recognition on reference plastic, above 300 µm and an 84% pixel recognition on household polyethylene plastic. When applied to environmental samples the technique showed an increase in identified particles compared with visual investigations. These initial tests indicate a potential underestimation of microplastics in environmental samples. This is the first study to demonstrate that hyperspectral imaging techniques can be used to study microplastics down to 300µm, which is a common size limit used in microplastic surveys.
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| 5. |
- Saenz Mendez, Patricia, et al.
(författare)
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Homology models of human all-trans retinoic acid metabolizing enzymes CYP26B1 and CYP26B1 spliced-variant.
- 2012
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Ingår i: Journal of Chemical Information and Modeling. - Washington, USA : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 52:10, s. 2631-2637
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Tidskriftsartikel (refereegranskat)abstract
- Homology models of CYP26B1 (cytochrome P450RAI2) and CYP26B1 spliced variant were derived using the crystal structure of cyanobacterial CYP120A1 as template for the model building. The quality of the homology models generated were carefully evaluated, and the natural substrate all-trans-retinoic acid (atRA), several tetralone-derived retinoic acid metabolizing blocking agents (RAMBAs), and a well-known potent inhibitor of CYP26B1 (R115866) were docked into the homology model of full-length cytochrome P450 26B1. The results show that in the model of the full-length CYP26B1, the protein is capable of distinguishing between the natural substrate (atRA), R115866, and the tetralone derivatives. The spliced variant of CYP26B1 model displays a reduced affinity for atRA compared to the full-length enzyme, in accordance with recently described experimental information.
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| 6. |
- Matxain, Jon M, et al.
(författare)
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Theoretical study of the reaction of vitamin B6 with 1O2
- 2007
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Ingår i: Chemistry - A European Journal. - Weinheim : Wiley-VCH Verlag. - 0947-6539 .- 1521-3765. ; 13:16, s. 4636-42
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Tidskriftsartikel (refereegranskat)abstract
- Singlet oxygen is known to cause oxidative stress in cells, leading to severe damage (e.g., lipid peroxidation, membrane degradation, mutagenic alterations to DNA, protein misfunctionality). Recently, pyridoxine has been discovered to be capable of quenching singlet oxygen, however, the mechanism of this reaction remains essentially unknown. In this work, we have investigated four sets of reactions: 1) 1,3-addition to a double bond connected to a hydrogen-carrying group,resulting in the formation of allylic hydroperoxides; 2) [p2+p2] 1,2-cycloaddition to an isolated double bond, resulting in the formation of 1,2-peroxides; 3) 1,4-cycloaddition to a system containing at least two conjugated double bonds, resulting in the formation of the so-called 1,4-peroxides;4) 1,4-addition to phenols and naphthols with the formation of hydroperoxide ketones. Thermodynamically, reaction 4 and the 6(9), 3(8), and 5(8) cases of reaction 1 are the most exergonic ones, with energies ranging from 16 to 18 kcalmol 1. Furthermore, reaction 4 shows the lowest barrier through the reaction path, and is predicted to be the preferred mechanismfor the pyridoxine + singlet-oxygen reaction, which is in agreement with previous experimental results.
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| 7. |
- Lyubartsev, Alexander, 1962-, et al.
(författare)
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Hierarchical multiscale modelling scheme from first principles to mesoscale
- 2009
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Ingår i: Journal of Computational and Theoretical Nanoscience. - : American Scientific Publishers. - 1546-1955 .- 1546-1963. ; 6:5, s. 951-959
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Tidskriftsartikel (refereegranskat)abstract
- We present a straight-forward implementation of a practical hierarchical multiscale modelling scheme which enables us to start from first-principles atomistic computer simulation and successively coarse-grain the model by leaving out uninteresting degrees of freedom. Using the Car-Parrinello method or our recently developed highly efficient tight-binding-like approximate density-functional quantum mechanical method,w e first perform first-principles simulations we obtain a set of atomistic pair-wise effective interaction potentials to be used as a force field with scaling up the system size 2–3 orders of magnitude. The atomistic simulations similarly provide a new set of effective potentials but at a chosen coarse-grain level suitable for large-scale mesoscopic or soft-matter simulations beyond the atomic resolution. Show several examples are shown of how this scheme is done based on effective interaction potentials to tie together the various scales of modelling.
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| 8. |
- Saenz-Mendez, Patricia, et al.
(författare)
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Theoretical study of sequence selectivity and preferred binding mode of psoralen with DNA
- 2007
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Ingår i: Research Letters in Physical Chemistry. - : Hindawi Limited. - 1687-6873 .- 1687-6881. ; , s. Article number 60623-
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Tidskriftsartikel (refereegranskat)abstract
- Psoralen interaction with two models of DNA was investigated using molecular mechanics and molecular dynamics methods. Calculated energies of minor groove binding and intercalation were compared in order to define a preferred binding mode for the ligand.We found that both binding modes are possible, explaining the low efficiency for monoadduct formation from intercalated ligands. A comparison between the interaction energy for intercalation between different base pairs suggests that the observed sequence selectivity is due to favorable intercalation in 5'-TpA in (AT)n sequences.
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| 9. |
- Khalaf, Hazem, et al.
(författare)
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Diastereomers of the Brominated Flame Retardant 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane Induce Androgen Receptor Activation in the HepG2 Hepatocellular Carcinoma Cell Line and the LNCaP Prostate Cancer Cell Line
- 2009
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Science. - 0091-6765 .- 1552-9924. ; 117:12, s. 1853-1859
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reported incidences of prostate cancer and masculinization of animals indicate a release of compounds with androgenic properties into the environment. Large numbers of environmental pollutants have been screened to identify such compounds; however, not until recently was 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) identified as the first potent activator of the human androgen receptor (hAR). TBECH has been found in beluga whales and bird eggs and has also been found to be maternally transferred in zebrafish.Objectives: In the present study we investigated interaction energies between TBECH diastereomers (α, β, γ, and δ) and the hAR, and their ability to activate the receptor and induce prostate-specific antigen (PSA) expression in vitro.Methods: We performed computational modeling to determine interaction energies between the ligand and the AR ligand-binding site, and measured in vitro competitive binding assays for AR by polarization fluorometry analysis. We used enzyme-linked immunosorbent assays to determine PSA activity in LNCaP and HepG2 cells.Results: We found the γ and δ diastereomers to be more potent activators of hAR than the α and β diastereomers, which was confirmed in receptor binding studies. All TBECH diastereomers induced PSA expression in LNCaP cells even though the AR present in these cells is mutated (T877A). Modeling studies of LNCaP AR revealed that TBECH diastereomers bound to the receptor with a closer distance to the key amino acids in the ligand-binding domain, indicating stronger binding to the mutated receptor.Conclusions: The present study demonstrates the ability of TBECH to activate the hAR, indicating that it is a potential endocrine disruptor.
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| 10. |
- Kännaste, Astrid, et al.
(författare)
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Odors of Norway spruce (Picea abies L.) seedlings : differences due to age and chemotype
- 2013
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Ingår i: Trees. - : Springer. - 0931-1890 .- 1432-2285. ; 27, s. 149-159
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Tidskriftsartikel (refereegranskat)abstract
- Small conifer seedlings (mini-seedlings) are less damaged by the large pine weevil Hylobius abietis (L.) (Coleoptera: Curculionidae) compared to conventional seedlings. Chemical difference between the seedling types is one possible explanation for this phenomenon. In the present paper, the emissions of volatile organic compounds (VOC) of 7- to 43-week-old Norway spruce [Picea abies (L.) Karst.] seedlings were analyzed. Collection and identification of the volatiles was made by solid phase micro-extraction and gas chromatography mass spectrometry (SPME–GC–MS). The enantiomers of α-pinene and limonene were separated in a two-dimensional GC (2D-GC). Most of the seedlings represented either a limonene- or a bornyl acetate-chemotype. Only minor changes in the volatile composition of the two types of seedlings were found during the first year. Age-related changes, however, were found in the volatiles released by wounded phloem where green leaf volatiles (GLVs) and borneol were the dominated VOC for young seedling. The attractive compound for the pine weevil, α-pinene, was first detected in the phloem emissions of 18- to 22-week-old seedlings. Different storage conditions of the seedlings during the winter/early spring-phase influenced the volatile composition in the phloem. High amount of GLVs was characteristic for the 43-week-old seedlings stored in naturally changing outdoor temperature, but not present in the seedlings winter-stored at a constant temperature of −4 °C. The possible role of these observed differences in odor emissions between seedlings of different age and physiological status for the feeding preferences of the large pine weevil is discussed.
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