| 1. |
- Bach, Anders, et al.
(författare)
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A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:9, s. 3317-3322
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
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| 2. |
- Rousk, Kathrin, et al.
(författare)
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Across-Habitat Comparison of Diazotroph Activity in the Subarctic
- 2015
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Ingår i: Microbial Ecology. - : Springer Science and Business Media LLC. - 0095-3628 .- 1432-184X. ; 69:4, s. 778-787
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Tidskriftsartikel (refereegranskat)abstract
- Nitrogen (N) fixation by N-2-fixing bacteria (diazotrophs) is the primary N input to pristine ecosystems like boreal forests and subarctic and arctic tundra. However, the contribution by the various diazotrophs to habitat N-2 fixation remains unclear. We present results from in situ assessments of N-2 fixation of five diazotroph associations (with a legume, lichen, feather moss, Sphagnum moss and free-living) incorporating the ground cover of the associations in five typical habitats in the subarctic (wet and dry heath, polygon-heath, birch forest, mire). Further, we assessed the importance of soil and air temperature, as well as moisture conditions for N-2 fixation. Across the growing season, the legume had the highest total as well as the highest fraction of N-2 fixation rates at habitat level in the heaths (> 85 % of habitat N-2 fixation), whereas the free-living diazotrophs had the highest N-2 fixation rates in the polygon heath (56 %), the lichen in the birch forest (87 %) and Sphagnum in the mire (100 %). The feather moss did not contribute more than 15 % to habitat N-2 fixation in any of the habitats despite its high ground cover. Moisture content seemed to be a major driver of N-2 fixation in the lichen, feather moss and free-living diazotrophs. Our results show that the range of N-2 fixers found in pristine habitats contribute differently to habitat N-2 fixation and that ground cover of the associates does not necessarily mirror contribution.
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