| 1. |
- Heiden, Marina, et al.
(författare)
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Evaluation of cognitive behavioural training and physical activity for patients with stress-related illnesses : a randomized controlled study
- 2007
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081 .- 0001-5555. ; 39:5, s. 366-373
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the effects of a cognitive behavioural training programme and a physical activity programme for patients with stress-related illnesses. DESIGN: In a randomized controlled study, patients were allocated randomly to 1 of 3 groups, where group 1 participated in a cognitive behavioural training programme, group 2 participated in a physical activity programme, and group 3, the control group, was offered usual care for the course of the study. SUBJECTS: A total of 75 patients participated in the study. They had been on sick leave for at least 50% of the time for between 1 month and 2 years due to stress-related illnesses. METHODS: Measurements of autonomic activity, pressure-pain thresholds and subjective ratings of health and behaviour were made before and after a 10-week intervention period, and at 6 and 12 months after the intervention. RESULTS: Minor differences in autonomic activity and pressure-pain thresholds were found between the groups immediately after the intervention. At the 6- and 12-month follow-up assessments, the differences were no longer present. Patients in the cognitive behavioural training group improved their ratings of general health compared with the physical activity group throughout the study. CONCLUSION: The study showed little difference in the effect of cognitive behavioural training and physical activity, compared with usual care, for patients with stress-related illnesses.
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| 2. |
- Söderström, Margareta, et al.
(författare)
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The quality of the outdoor environment influences children's health. -A cross-sectional study of preschools.
- 2013
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 102:1, s. 83-91
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To test how the quality of the outdoor environment of child day care centers (DCCs) influences children's health. METHODS: The environment was assessed using the Outdoor Play Environmental Categories (OPEC) tool; time spent outdoors, and physical activity as measured by pedometer. 172/253 (68%) of children aged 3.0-5.9 from nine DCCs participated in Southern Sweden. Health data collected were body mass index, waist circumference, saliva cortisol, length of night sleep during study, and symptoms and wellbeing which were scored (one-week diary- 121 parent responders). Also, parent-rated wellbeing and health of their child were scored (questionnaire, 132 parent responders). MANOVA, ANOVA and principal component analyses were performed to identify impacts of the outdoor environment on health. RESULTS: High quality outdoor environment at DCCs is associated with several health aspects in children such as leaner body, longer night sleep, better wellbeing and higher mid-morning saliva cortisol levels. CONCLUSION: The quality of the outdoor environment at DCCs influenced the health and wellbeing of preschool children and should be given more attention among health care professionals and community planners. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
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| 3. |
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| 4. |
- Aurelius, Oskar, et al.
(författare)
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The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, the building blocks for DNA synthesis, and are found in all but a few organisms. RNRs use radical chemistry to catalyze the reduction reaction. Despite RNR having evolved several mechanisms for generation of different kinds of essential radicals across a large evolutionary time frame, this initial radical is normally always channelled to a strictly conserved cysteine residue directly adjacent to the substrate for initiation of substrate reduction, and this cysteine has been found in the structures of all RNRs solved to date. We present the crystal structure of an anaerobic RNR from the extreme thermophile Thermotoga maritima (tmNrdD), alone and in several complexes, including with the allosteric effector dATP and its cognate substrate CTP. In the crystal structure of the enzyme as purified, tmNrdD lacks a cysteine for radical transfer to the substrate pre-positioned in the active site. Nevertheless activity assays using anaerobic cell extracts from T. maritima demonstrate that the class III RNR is enzymatically active. Other genetic and microbiological evidence is summarized indicating that the enzyme is important for T. maritima. Mutation of either of two cysteine residues in a disordered loop far from the active site results in inactive enzyme. We discuss the possible mechanisms for radical initiation of substrate reduction given the collected evidence from the crystal structure, our activity assays and other published work. Taken together, the results suggest either that initiation of substrate reduction may involve unprecedented conformational changes in the enzyme to bring one of these cysteine residues to the expected position, or that alternative routes for initiation of the RNR reduction reaction may exist. Finally, we present a phylogenetic analysis showing that the structure of tmNrdD is representative of a new RNR subclass IIIh, present in all Thermotoga species plus a wider group of bacteria from the distantly related phyla Firmicutes, Bacteroidetes and Proteobacteria.
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| 5. |
- Berggren, Gustav, et al.
(författare)
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Compounds with capacity to quench the tyrosyl radical in Pseudomonas aeruginosa ribonucleotide reductase
- 2019
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 24:6, s. 841-848
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductase (RNR) has been extensively probed as a target enzyme in the search for selective antibiotics. Here we report on the mechanism of inhibition of nine compounds, serving as representative examples of three different inhibitor classes previously identified by us to efficiently inhibit RNR. The interaction between the inhibitors and Pseudomonas aeruginosa RNR was elucidated using a combination of electron paramagnetic resonance spectroscopy and thermal shift analysis. All nine inhibitors were found to efficiently quench the tyrosyl radical present in RNR, required for catalysis. Three different mechanisms of radical quenching were identified, and shown to depend on reduction potential of the assay solution and quaternary structure of the protein complex. These results form a good foundation for further development of P. aeruginosa selective antibiotics. Moreover, this study underscores the complex nature of RNR inhibition and the need for detailed spectroscopic studies to unravel the mechanism of RNR inhibitors.
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| 6. |
- Berggren, Gustav, et al.
(författare)
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Semiquinone-Induced Maturation of Bacillus anthracis Ribonucleotide Reductase by a Superoxide Intermediate
- 2014
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Ingår i: Journal of Biological Chemistry.
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides, and represent the only de novo pathway to provide DNA building blocks. Three different classes of RNR are known, denoted I-III. Class I RNRs are heteromeric proteins built up by α and β subunits and are further divided into different subclasses, partly based on the metal content of the β-subunit. In subclass Ib RNR the β-subunit is denoted NrdF, and harbors a manganese-tyrosyl radical cofactor. The generation of this cofactor is dependent on a flavodoxin-like maturase denoted NrdI, responsible for the formation of an active oxygen species suggested to be either a superoxide or a hydroperoxide. Herein we report on the magnetic properties of the manganese-tyrosyl radical cofactor of Bacillus anthracis NrdF and the redox properties of B. anthracis NrdI. The tyrosyl radical in NrdF is stabilized through its interaction with a ferromagnetically coupled manganese dimer. Moreover, we show through a combination of redox titration and protein electrochemistry that in contrast to hitherto characterized NrdIs, the B. anthracis NrdI is stable in its semiquinone form (NrdIsq) with a difference in electrochemical potential of approximately 110 mV between the hydroquinone and semiquinone state. The under anaerobic conditions stable NrdIsq is fully capable of generating the oxidized, tyrosyl radical-containing form of Mn-NrdF when exposed to oxygen. This latter observation strongly supports that a superoxide radical is involved in the maturation mechanism, and contradicts the participation of a peroxide species. Additionally, EPR spectra on whole cells revealed that a significant fraction of NrdI resides in its semiquinone form in vivo, underscoring that NrdIsq is catalytically relevant.
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| 7. |
- Berggren, Gustav, et al.
(författare)
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Semiquinone-induced Maturation of Bacillus anthracis Ribonucleotide Reductase by a Superoxide Intermediate
- 2014
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:46, s. 31940-31949
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of ribonucleotide reductase Ib depends on the flavodoxin-like maturase NrdI.Results: The redox properties of Bacillus anthracis NrdI allow isolation of the semiquinone state, NrdI(sq), which can catalyze formation of the manganese-tyrosyl radical cofactor.Conclusion: The maturation capacity of NrdI(sq) provides evidence that Mn-NrdF is activated via a superoxide radical.Significance: Novel antibiotics may be designed to selectively target the maturation mechanism.
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| 8. |
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| 9. |
- Crona, Mikael, et al.
(författare)
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A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:12, s. 8198-8208
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the only pathway for de novo synthesis of deoxyribonucleotides needed for DNA replication and repair. The vast majority of eukaryotes encodes only a class I RNR, but interestingly some eukaryotes, including the social amoeba Dictyostelium discoideum, encode both a class I and a class II RNR. The amino acid sequence of the D. discoideum class I RNR is similar to other eukaryotic RNRs, whereas that of its class II RNR is most similar to the monomeric class II RNRs found in Lactobacillus spp. and a few other bacteria. Here we report the first study of RNRs in a eukaryotic organism that encodes class I and class II RNRs. Both classes of RNR genes were expressed in D. discoideum cells, although the class I transcripts were more abundant and strongly enriched during mid-development compared with the class II transcript. The quaternary structure, allosteric regulation, and properties of the diiron-oxo/radical cofactor of D. discoideum class I RNR are similar to those of the mammalian RNRs. Inhibition of D. discoideum class I RNR by hydroxyurea resulted in a 90% reduction in spore formation and decreased the germination viability of the surviving spores by 75%. Class II RNR could not compensate for class I inhibition during development, and an excess of vitamin B12 coenzyme, which is essential for class II activity, did not improve spore formation. We suggest that class I is the principal RNR during D. discoideum development and growth and is important for spore formation, possibly by providing dNTPs for mitochondrial replication.
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