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- Woitowich, N. C., et al.
(författare)
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Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
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- Edlund, Petra, et al.
(författare)
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The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
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- Axelsson, Christer, et al.
(författare)
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Outcome after out-of-hospital cardiac arrest witnessed by EMS : changes over time and factors of importance for outcome in Sweden.
- 2012
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Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 83:10, s. 1253-1258
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Tidskriftsartikel (refereegranskat)abstract
- Background Among patients who survive after out-of-hospital cardiac arrest (OHCA), a large proportion are recruited from cases witnessed by the Emergency Medical Service (EMS), since the conditions for success are most optimal in this subset. Aim To evaluate outcome after EMS-witnessed OHCA in a 20-year perspective in Sweden, with the emphasis on changes over time and factors of importance. Methods All patients included in the Swedish Cardiac Arrest Register from 1990 to 2009 were included. Results There were 48,349 patients and 13.5% of them were EMS witnessed. There was a successive increase in EMS-witnessed OHCA from 8.5% in 1992 to 16.9% in 2009 (p for trend < 0.0001). Among EMS-witnessed OHCA, the survival to one month increased from 13.9% in 1992 to 21.8% in 2009 (p for trend < 0.0001). Among EMS-witnessed OHCA, 51% were found in ventricular fibrillation, which was higher than in bystander-witnessed OHCA, despite a lower proportion with a presumed cardiac aetiology in the EMS-witnessed group. Among EMS-witnessed OHCA overall, 16.0% survived to one month, which was significantly higher than among bystander-witnessed OHCA. Independent predictors of a favourable outcome were: (1) initial rhythm ventricular fibrillation; (2) cardiac aetiology; (3) OHCA outside home and (4) decreasing age. Conclusion In Sweden, in a 20-year perspective, there was a successive increase in the proportion of EMS-witnessed OHCA. Among these patients, survival to one month increased over time. EMS-witnessed OHCA had a higher survival than bystander-witnessed OHCA. Independent predictors of an increased chance of survival were initial rhythm, aetiology, place and age.
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| 7. |
- Chang, J., et al.
(författare)
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Anisotropic breakdown of Fermi liquid quasiparticle excitations in overdoped La2-xSrxCuO4
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2559-
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Tidskriftsartikel (refereegranskat)abstract
- High-temperature superconductivity emerges from an un-conventional metallic state. This has stimulated strong efforts to understand exactly how Fermi liquids breakdown and evolve into an un-conventional metal. A fundamental question is how Fermi liquid quasiparticle excitations break down in momentum space. Here we show, using angle-resolved photoemission spectroscopy, that the Fermi liquid quasiparticle excitations of the overdoped superconducting cuprate La1.77Sr0.23CuO4 is highly anisotropic in momentum space. The quasiparticle scattering and residue behave differently along the Fermi surface and hence the Kadowaki-Wood's relation is not obeyed. This kind of Fermi liquid breakdown may apply to a wide range of strongly correlated metal systems where spin fluctuations are present.
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| 8. |
- Heller, T., et al.
(författare)
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Plasma concentrations of mycophenolic acid acyl glucuronide are not associated with diarrhea in renal transplant recipients
- 2007
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 7:7, s. 1822-1831
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.
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