| 51. |
- Ren, Yansong, et al.
(författare)
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A Multicontrolled Enamine Configurational Switch Undergoing Dynamic Constitutional Exchange
- 2018
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 57:21, s. 6256-6260
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Tidskriftsartikel (refereegranskat)abstract
- A multiresponsive enamine-based molecular switch is presented, in which forward/backward configurational rotation around the C=C bond could be precisely controlled by the addition of an acid/base or metal ions. Fluorescence turn-on/off effects and large Stokes shifts were observed while regulating the switching process with CuII. The enamine functionality furthermore enabled double dynamic regimes, in which configurational switching could operate in conjunction with constitutional enamine exchange of the rotor part. This behavior was used to construct a prototypical dynamic covalent switch system through enamine exchange with primary amines. The dynamic exchange process could be readily turned on/off by regulating the switch status with pH.
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| 52. |
- Ren, Yansong, et al.
(författare)
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Multistimuli-Responsive Enaminitrile Molecular Switches Displaying H+-Induced Aggregate Emission, Metal Ion-Induced Turn-On Fluorescence, and Organogelation Properties
- 2018
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:42, s. 13640-13643
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Tidskriftsartikel (refereegranskat)abstract
- Multistimuli-responsive enaminitrile-based configurational switches displaying aggregation-induced emission (AIE), fluorescence turn-on effects, and super gelation properties are presented. The E-isomers dominated (>97%) in neutral/basic solution, and the structures underwent precisely controlled switching around the enamine C=C bond upon addition of acid/base. Specific fluorescence output was observed in response to different external input in the solution and solid states. In response to H+, configurational switching resulted in complete formation of the nonemissive Z-H+-isomers in solution, however displaying deep-blue to blue fluorescence (Phi(F) up to 0.41) in the solid state. In response to Cu-II in the solution state, the E-isomers exhibited intense, turn-on, blue-green fluorescence, which could be turned off by addition of competitive coordination. The acid/base-activated switching, together with the induced AIE-effects, further enabled the accomplishment of a responsive superorganogelator. In nonpolar solvents, a blue-fluorescent supramolecular gel was formed upon addition of acid to the E-isomer suspension. The gelation could be reversed by addition of base, and the overall, reversible process could be repeated at least five cycles.
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| 53. |
- Ricklefs, Robert E, et al.
(författare)
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Avian migration and the distribution of malaria parasites in New World passerine birds
- 2017
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 44:5, s. 1113-1123
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Migrating birds transport their parasites, often over long distances, but little is known about the transfer of these parasites to resident hosts in either the wintering or breeding ranges of the migratory host populations. We investigated the haemosporidian parasite faunas of migratory and resident birds to determine connections among distant parasite faunas, plausibly brought about by migratory host populations. Location: Samples were obtained, primarily during or shortly after the local breeding season, throughout the Americas, from the United States through the Caribbean Basin and into northern South America. Methods: Infections were identified by PCR and sequencing of parasite DNA in avian blood samples. The analyses were based on c. 4700 infections representing 79 parasite lineages of Plasmodium and Haemoproteus spp. Geographical connections of lineages between regions in the Americas were compared to those in the Euro-African migration system, where migration distances are longer for many host species and the migrant and resident avifaunas in the wintering areas are phylogenetically more divergent. Results: Haemosporidian lineages exhibited considerable variation in distribution in the Americas, and patterns of distribution differ markedly between the Americas and the Euro-African migration system. In particular, few lineages were recovered from resident species in both temperate and tropical latitudes, particularly in the Euro-African system, in which a large proportion of lineages were restricted to migrants. Parasite lineages in the Euro-African system exhibited considerable phylogenetic conservatism in their distributions, that is, a tendency of related lineages to exhibit similar geographical distributions. In contrast, clades of parasites in the Americas displayed more geographical diversity, with four of 12 clades exhibiting all four of the distribution types representing the combinations of resident and migrant host species in both temperate and tropical latitudes. Main conclusions: Long-distance migrants connect communities of avian haemosporidian parasites in breeding and wintering areas with disparate avifaunas and different vector communities. The degree of parasite lineage sharing between migrants and residents in breeding and wintering areas appears to reflect, to a large degree, the taxonomic similarity of migrants to the resident species in both areas.
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| 54. |
- Safari, Reza, et al.
(författare)
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Impedance Matching for VSC-HVDC Damping Controller Gain Selection
- 2018
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Ingår i: IEEE Transactions on Power Systems. - 0885-8950.
-
Tidskriftsartikel (refereegranskat)abstract
- The impedance matching concept is employed in this paper to select the optimum gain of a VSC-HVDC damping controller. The damping controller of the DC link is based on control of active power in proportion to the difference in local frequency at the VSC-HVDC converter stations. To explain impedance matching, the small-disturbance electro-mechanical dynamics of a power system is transformed to an equivalent LC-circuit. The VSC-HVDC damping controller corresponds to introducing a resistor in the circuit model. Using impedance matching to select resistor value in the circuit model is equivalent to selecting damping controller gain that gives maximum damping ratio. An analytical derivation is conducted for a linearized model of a generic two-area power system, including an expression for the optimum gain. It is also shown how the concept may be employed without a circuit model and that the optimum value is hardly affected by changes in power flow. Then the performance of the proposed approach in multi-mode test systems and with nonlinearities is evaluated using dynamic simulations in DIgSILENT PowerFactory. The results show that impedance matching maximizes the targeted mode damping ratio while non-targeted modes are not negatively impacted.
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| 55. |
- Safari Tirtashi, Mohammad Reza, et al.
(författare)
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Impedance Matching for VSC-HVDC and Energy Storage Damping Controllers
- 2018
-
Ingår i: IEEE Transactions on Power Delivery. - 0885-8977. ; 33:2, s. 1016-1017
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Tidskriftsartikel (refereegranskat)abstract
- The small-disturbance electro-mechanical dynamics of a power system can be translated to an equivalent circuit model with inductances and capacitances. Damping control of active power in proportion to local frequency as with a VSC-HVDC link or an energy storage then corresponds to introducing a resistor in the circuit model. This letter shows that impedance matching can be used to select resistor value, and equivalently damping controller gain, that gives maximum damping ratio. It is also shown how the concept is employed without a circuit model.
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| 56. |
- Svensson, Daniel, et al.
(författare)
-
Apolipoprotein A-I attenuates LL-37-induced endothelial cell cytotoxicity
- 2017
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 493:1, s. 71-76
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Tidskriftsartikel (refereegranskat)abstract
- The human cathelicidin peptide LL-37 has antimicrobial and anti-biofilm functions, but LL-37 may also damage the host by triggering inflammation and exerting a cytotoxic effect, thereby reducing host cell viability. Human plasma mitigates LL-37-induced host cell cytotoxicity but the underlying mechanisms are not completely understood. Apolipoprotein A-I (ApoA-I) is a plasma protein endowed with atheroprotective effects. Here, we investigate the interaction between ApoA-I and LL-37 by biochemical techniques, and furthermore assess if ApoA-I protects against LL-37-evoked cytotoxicity in human umbilical vein endothelial cells (HUVEC). Our results demonstrated that ApoA-I effectively binds LL-37. The binding of ApoA-I to LL-37 resulted in a structural rearrangement of the protein, but this interaction did not cause lower ApoA-I stability. Recombinant ApoA-I protected against LL-37-induced cytotoxicity in HUVEC and endogenous ApoA-I knockdown in HepG2 cells made the cells more sensitive to LL-37-evoked cytotoxicity. We conclude that ApoA-I physically interacts with LL-37 and antagonizes LL-37-induced down-regulation of endothelial cell viability suggesting that this mechanism counteracts endothelial cell dysfunction.
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| 57. |
- Svensson, Daniel, et al.
(författare)
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Human endogenous peptide p33 inhibits detrimental effects of LL-37 on osteoblast viability
- 2015
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Ingår i: Journal of Periodontal Research. - : John Wiley & Sons. - 0022-3484 .- 1600-0765. ; 50:1, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: High levels of the antimicrobial peptide, LL-37, are detected in gingival crevicular fluid from patients with chronic periodontitis. LL-37 not only shows antimicrobial activity but also affects host-cell viability. The objective of the present study was to identify endogenous mechanisms that antagonize the detrimental effects of LL-37 on osteoblast viability, focusing on the human peptide p33 expressed on the surface of various cell types. Material and Methods: Human osteoblast-like MG63 cells and human hFOB1.19 osteoblasts were treated with or without LL-37 in the presence or absence of p33. Recombinant human p33 was expressed in an Escherichia coli expression system. Lactate dehydrogenase (LDH) was assessed using an enzymatic spectrophotometric assay. DNA synthesis was determined by measuring [3H]-thymidine incorporation. Cell number was assessed by counting cells in a Bu€rker chamber. Intracellular Ca2+ was monitored by recording Fluo 4-AM fluorescence using a laser scanning confo- cal microscope. Cellular expression of p33 was determined by western blotting. Results: LL-37 caused a concentration-dependent release of LDH from human osteoblasts, showing a half-maximal response value (EC50) of 4 lM and a rapid and sustained rise in the intracellular Ca2+ concentration of osteoblasts, sug- gesting that LL-37 forms pores in the cell membrane. p33 (10 lM) inhibited the LL-37-induced LDH release and LL-37-evoked rise in intracellular Ca2+ con- centration, suggesting that p33 prevents LL-37-induced permeabilization of the cell membrane. Moreover, p33 blocked LL-37-induced attenuation of osteoblast numbers. Also, mucin antagonized, at concentrations representative for nonsti- mulated whole saliva, LL-37-evoked LDH release, whilst cationic endogenous polyamines had no impact on LL-37-induced LDH release from osteoblasts. Conclusions: The endogenous peptide p33 prevents LL-37-induced reduction of human osteoblast viability. Importantly, this mechanism may protect the osteo- blasts from LL-37-induced cell damage in patients suffering from chronic peri- odontitis associated with high levels of LL-37 locally.
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| 58. |
- Svensson, Daniel, et al.
(författare)
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LL-37-induced host cell cytotoxicity depends on cellular expression of the globular C1q receptor (p33).
- 2016
-
Ingår i: The Biochemical journal. - 1470-8728. ; 473, s. 87-98
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Tidskriftsartikel (refereegranskat)abstract
- The human host-defense peptide LL-37 not only displays antimicrobial activity but also immune modulating properties that trigger intracellular signaling events in host cells. Since the cytolytic activity of high LL-37 concentrations affects cell viability, the function of LL-37 requires tight regulation. Eukaryotic cells therefore benefit from protective measures to prevent harmful effects of LL-37. p33, also known as globular C1q receptor, is reported to act as an LL-37 antagonist by binding the peptide thereby reducing its cytotoxic activity. In this report, we show that high levels of endogenous p33 correlate with an increased viability in human cells treated with LL-37. Sub-cellular localization analysis showed p33 distribution at the mitochondria, the plasma membrane and in the cytosol. Strikingly, cytosolic over-expression of p33 significantly antagonized detrimental effects of LL-37 on cell fitness, while the reverse effect was observed by siRNA-induced down-regulation of p33. However, modulation of p33 expression had no effect on LL-37-induced plasma membrane pore forming capacity pointing to an intracellular mechanism. A scavenging function of intracellular p33 is further supported by co-immunoprecipitation experiments, showing a direct interaction between intracellular p33 and LL-37. Thus, our findings support an important role of intracellular p33 in maintaining cell viability by counteracting LL-37-induced cytotoxicity.
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| 59. |
- Svensson, Daniel, et al.
(författare)
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Secretory leukocyte protease inhibitor regulates human periodontal ligament cell production of pro-inflammatory cytokines
- 2017
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1023-3830 .- 1420-908X. ; 66:9, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Regulation of immune-like cell properties of periodontal ligament (PDL) cells is not understood. We investigate the importance of secretory leukocyte protease inhibitor (SLPI) for production of pro-inflammatory cytokines in human PDL cells. Materials and methods: PDL cells were isolated from teeth extracted for orthodontic reasons. Cellular location of SLPI was investigated by immunocytochemistry. Cytokine transcript and protein expression were assessed by quantitative real-time RT-PCR and Western blotting. SLPI gene activity was knocked-down by siRNA. NF-κB signaling was assessed by measuring IκBα, and phosphorylated p65 and p105 protein expression. Results: PDL cells showed cytoplasmic expression of SLPI. Cellular expression level of SLPI negatively correlated to LPS-induced stimulation of IL-6 and MCP-1. Both SLPI gene activity and protein were reduced by about 70% in PDL cells treated with SLPI siRNA compared to cells treated with non-coding construct. Treatment with SLPI siRNA was associated with up-regulation of both basal and LPS-stimulated IL-6, MCP-1 and TLRs mRNA expression. The up-regulation of MCP-1 transcript in SLPI siRNA-treated cells was confirmed on protein level. SLPI siRNA-treatment enhanced the phosphorylated NF-κB p105 protein expression. Conclusions: SLPI regulates PDL cell pro-inflammatory cytokine expression and modulates NF-κB signaling, suggesting that SLPI governs the immune cell-like properties of PDL cells.
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| 60. |
- Svensson, Daniel, et al.
(författare)
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Sesquiterpene lactones from Ambrosia arborescens Mill. inhibit pro-inflammatory cytokine expression and modulate NF-κB signaling in human skin cells
- 2018
-
Ingår i: Phytomedicine. - : Elsevier BV. - 0944-7113. ; 50, s. 118-126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ambrosia arborescens has been used in Andean traditional medicine to reduce problems associated with various inflammatory diseases and conditions, although the underlying mechanism is unknown. Hypothesis/purpose: The sesquiterpene lactones (SLs) coronopilin and damsin, which are major secondary metabolites of A. arborescens, have anti-inflammatory activity by attenuation of IL-6 and MCP-1 expression and inhibition of NF-κB in human dermal fibroblasts (HDFa) and human keratinocytes (HaCaT). Study design: In order to confirm a high concentration of damsin and coronopilin in the plant material, a quantitative method was developed. The effect of the pure compounds on cytokine and NF-κB expression was examined, as well as their effects on HDFa and HaCaT cell morphology and viability. Methods: Coronopilin and damsin were quantified by HPLC-DAD analysis, from EtOAc extracts of the aerial parts of A. arborescens. Cell morphology was investigated by phase-contrast microscopy and cell viability by the MTT assay. IL-6 and MCP-1 cytokine gene expression was assessed by quantitative real-time RT-PCR in LPS stimulated cells. The NF-κB pathway was studied through western blotting of the phosphorylated forms of p65 and p50/p105, as well as the non-phosphorylated IκB. Dexamethasone was used as positive control. Results: Dry aerial parts contained 12.3 mg/g and 13.4 mg/g of coronopilin and damsin, respectively. Treatment with either compound (1–10 µM) for 24 h attenuated LPS-induced mRNA expression of the pro-inflammatory cytokine IL-6 and the chemokine MCP-1 in HDFa cells. The down-regulation of MCP-1 mRNA induced by coronopilin and damsin was confirmed on the protein level. Damsin reduced phosphorylated p65 and p105 subunits in HDFa cells. Neither coronopilin nor damsin affected HDFa cell morphology and viability within the used concentration range (1–10 µM). Also, in HaCaT cells, treatment with damsin (1–10 µM) for 24 h inhibited the MCP-1 expression, and damsin thereby attenuated cytokine expression both in HDFa and HaCaT cells. Conclusion: We show that coronopilin and damsin from A. arborescens inhibit pro-inflammatory IL-6 and MCP-1 expression in human skin cells via NF-κB inhibition, suggesting that they may be useful for antagonizing inflammatory conditions of the human skin.
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