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| 2. |
- Johnson, Magnus S.C. 1969, et al.
(författare)
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Interaction of scavenger receptor class B type I with peroxisomal targeting receptor Pex5p.
- 2003
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Ingår i: Biochemical and biophysical research communications. - 0006-291X. ; 312:4, s. 1325-34
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Tidskriftsartikel (refereegranskat)abstract
- Scavenger receptor class B type I (SR-BI) is an HDL receptor that mediates selective HDL lipid uptake. Peroxisomes play an important role in lipid metabolism and peroxisomal targeting signal type 1 (PTS1)-containing proteins are translocated to peroxisomes by the peroxisomal targeting import receptor, Pex5p. We have previously identified a PTS1 motif in the intracellular domain of rat SR-BI. Here, we examine the possible interaction between Pex5p and SR-BI. Expression of a Flag-tagged intracellular domain of SR-BI resulted in translocation to the peroxisome as demonstrated by double labeling with anti-Flag IgG and anti-catalase IgG analyzed by confocal microscopy. Immunoprecipitation experiments with anti-SR-BI antibody showed that Pex5p co-precipitated with SR-BI. However, when an antibody against Pex5p was used for immunoprecipitation, only the 57kDa, non-glycosylated form, of SR-BI co-precipitated. We conclude that the PTS1 domain of SR-BI is functional and can mediate peroxisomal interaction via Pex5p, in vitro.
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| 3. |
- Nissen, Klaus B., et al.
(författare)
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Targeting Protein-Protein Interactions with Trimeric Ligands : High Affinity Inhibitors of the MAGUK Protein Family
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- PDZ domains in general, and those of PSD-95 in particular, are emerging as promising drug targets for diseases such as ischemic stroke. We have previously shown that dimeric ligands that simultaneously target PDZ1 and PDZ2 of PSD-95 are highly potent inhibitors of PSD-95. However, PSD-95 and the related MAGUK proteins contain three consecutive PDZ domains, hence we envisioned that targeting all three PDZ domains simultaneously would lead to more potent and potentially more specific interactions with the MAGUK proteins. Here we describe the design, synthesis and characterization of a series of trimeric ligands targeting all three PDZ domains of PSD-95 and the related MAGUK proteins, PSD93, SAP-97 and SAP-102. Using our dimeric ligands targeting the PDZ1-2 tandem as starting point, we designed novel trimeric ligands by introducing a PDZ3-binding peptide moiety via a cysteine-derivatized NPEG linker. The trimeric ligands generally displayed increased affinities compared to the dimeric ligands in fluorescence polarization binding experiments and optimized trimeric ligands showed low nanomolar inhibition towards the four MAGUK proteins, thus being the most potent inhibitors described. Kinetic experiments using stopped-flow spectrometry showed that the increase in affinity is caused by a decrease in the dissociation rate of the trimeric ligand as compared to the dimeric ligands, likely reflecting the lower probability of simultaneous dissociation of all three PDZ ligands. Thus, we have provided novel inhibitors of the MAGUK proteins with exceptionally high affinity, which can be used to further elucidate the therapeutic potential of these proteins.
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| 4. |
- Svensson, C. E., et al.
(författare)
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Collective rotational motion in the N=Z nucleus 36Ar
- 2001
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Ingår i: Nuclear Physics A. - 0375-9474. ; 682:1-4, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- A superdeformed rotational band has been identified in the N = Z nucleus 36Ar, firmly linked to known low-spin states, and observed to its high-spin termination at Iπ = 16+. Lifetime measurements by the Doppler shift attenuation method establish a large low-spin deformation (β2 ≈ 0.46) and a decrease in the collectivity as the band approaches termination. Comparisons with cranked Nilsson-Strutinsky and large-scale spherical shell model calculations lead to a consistent description of the band based on a configuration in which four particles are promoted to the pf shell. With two major shells active for both protons and neutrons, yet a valence space dimension small enough to be approached from the shell model perspective, this band offers an excellent opportunity to investigate the microscopic structure of collective rotational motion in nuclei.
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| 5. |
- Svensson, C. E., et al.
(författare)
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Superdeformation in the N = z Nucleus 36Ar : Experimental, deformed mean field, and spherical shell model descriptions
- 2000
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Ingår i: Physical Review Letters. - 0031-9007. ; 85:13, s. 2693-2696
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Tidskriftsartikel (refereegranskat)abstract
- A superdeformed rotational band has been identified in 36Ar, linked to known low-spin states, and observed to its high-spin termination at Iπ = 16+. Cranked Nilsson-Strutinsky and spherical shell model calculations assign the band to a configuration in which four pf-shell orbitals are occupied, leading to a low-spin deformation β2 ≈ 0.45. Two major shells are active for both protons and neutrons, yet the valence space remains small enough to be confronted with the shell model. This band thus provides an ideal case to study the microscopic structure of collective rotational motion.
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| 7. |
- Airoldi, L., et al.
(författare)
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An ecological perspective on the deployment and design of low-crested and other hard coastal defence structures
- 2005
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Ingår i: Coastal Engineering. - : Elsevier BV. - 0378-3839. ; 52:10-11, s. 1073-1087
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Tidskriftsartikel (refereegranskat)abstract
- Coastal areas play a crucial role in the economical, social and political development of most countries; they support diverse and productive coastal ecosystems that provide valuable goods and services. Globally flooding and coastal erosion represent serious threats along many coastlines, and will become more serious as a consequence of human-induced changes and accelerated sea-level rise. Over the past century, hard coastal defence structures have become ubiquitous features of coastal landscapes as a response to these threats. The proliferation of defence works can affect over half of the shoreline in some regions and results in dramatic changes to the coastal environment. Surprisingly little attention has been paid to the ecological consequences of coastal defence. Results from the DELOS (Environmental Design of Low Crested Coastal Defence Structures, EVK3-CT-2000-00041) project indicate that the construction of coastal defence structures will affect coastal ecosystems. The consequences can be seen on a local scale, as disruption of surrounding soft-bottom environments and introduction of new artificial hard-bottom habitats, with consequent changes to the native assemblages of the areas. Proliferation of coastal defence structures can also have critical impacts on regional species diversity, removing isolating barriers, favouring the spread of non-native species and increasing habitat heterogeneity. Knowledge of the environmental context in which coastal defence structures are placed is fundamental to an effective management of these structures as, while there are some general consequences of such construction, many effects are site specific. Advice is provided to meet specific management goals, which include mitigating specific impacts on the environment, such as minimising changes to surrounding sediments, spread of exotic species or growth of nuisance species, and/or enhancing specific natural resources, for example enhancing fish recruitment or promoting diverse assemblages for eco-tourism. The DELOS project points out that the downstream effects of defence structures on coastal processes and regional-scale impacts on biodiversity necessitate planning and management at a regional (large coastline) scale. To effectively understand and manage coastal defences, environmental management goals must be clearly stated and incorporated into the planning, construction, and monitoring stages. (c) 2005 Elsevier B.V. All rights reserved.
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| 8. |
- Cegelski, Lynette, et al.
(författare)
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Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
- 2009
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type1pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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| 9. |
- Cox, D. M., et al.
(författare)
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Spectroscopy along flerovium decay chains. II. Fine structure in odd-A 289Fl
- 2023
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Ingår i: Physical Review C. - 2469-9985. ; 107:2
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Tidskriftsartikel (refereegranskat)abstract
- Fifteen correlated α-decay chains starting from the odd-A superheavy nucleus 289Fl were observed following the fusion-evaporation reaction 48Ca+244Pu. The results call for at least two parallel α-decay sequences starting from at least two different states of 289Fl. This implies that close-lying levels in nuclei along these chains have quite different spin-parity assignments. Further, observed α-electron and α-photon coincidences, as well as the α-decay fine structure along the decay chains, suggest a change in the ground-state spin assignment between 285Cn and 281Ds. Our experimental results, on the excited level structure of the heaviest odd-N nuclei to date, provide a direct testing ground for theory. This is illustrated by comparison with new nuclear structure calculations based on the symmetry-conserving configuration mixing theory.
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| 10. |
- Hawkins, Stephen J., et al.
(författare)
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The Intertidal Zone of the North-East Atlantic Region
- 2019
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Ingår i: Interactions in the Marine Benthos: Global Patterns and Processes (Systematics Association Special Volume Series, pp. 7-46). - : Cambridge university press. - 9781108416085
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Bokkapitel (refereegranskat)abstract
- The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
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