| 1. |
- Larsson, Karl-Magnus, et al.
(författare)
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Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase
- 2004
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 11:11, s. 1142-1149
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis and repair. Imbalances in these pools increase mutational rates and are detrimental to the cell. Balanced precursor pools are maintained primarily through the regulation of the RNR substrate specificity. Here, the molecular mechanism of the allosteric substrate specificity regulation is revealed through the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes with four effector-substrate nucleotide pairs and in three complexes with only effector. The mechanism is based on the flexibility of loop 2, a key structural element, which forms a bridge between the specificity effector and substrate nucleotides. Substrate specificity is achieved as different effectors and their cognate substrates stabilize specific discrete loop 2 conformations. The mechanism of substrate specificity regulation is probably general for most class I and class II RNRs.
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| 2. |
- Bredenberg, Johan, et al.
(författare)
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Modeling zinc sulfhydryl bonds in zinc fingers
- 2001
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Ingår i: International Journal of Quantum Chemistry. - : Wiley. - 0020-7608 .- 1097-461X. ; 83:3-4, s. 230-244
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Tidskriftsartikel (refereegranskat)abstract
- Molecular dynamics simulations have been carried out employing three different model descriptions of the zinc sulfhydryl interactions in class II fingers. One bonded and two nonbonded models were studied. Two variant structures of the glucocorticoid receptor DNA-binding; domain and a NMR structure from a fragment of methionyl-tRNA synthetase were subjected to long-time MD simulations with these models. Our analysis is focused on comparison with experimental and quantum mechanical data, concerning the local Zn-finger and overall structural and dynamic properties for these models. All models performed M ell, but the nonbonded models appeared to reproduce the protein dynamics in better agreement with experimental data than does the bonded description.
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| 3. |
- Grimm, T, et al.
(författare)
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Genomic organization and embryonic expression of Suppressor of Fused, a candidate gene for the split-hand/split-foot malformation type 3
- 2001
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 505:1, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- The genes for human and mouse Suppressor of Fused (SU(FU)/Su(Fu)) in the Hedgehog signaling pathway were characterized and found to contain 12 exons. Human SU(FU) localized on chromosome 10q24-25 between the markers D10S192 and AFM183XB12. We detected three additional SU(FU) isoforms, two of which have lost their ability to interact with the transcription factor GLI1. Expression analysis using whole mount in situ hybridization revealed strong expression of Su(Fu) in various mouse embryonic tissues. SU(FU) was considered a candidate gene for the split-hand/split-foot malformation type 3 (SHFM3). However, no alterations in the SU(FU) gene were found in SHFM3 patients.
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| 4. |
- Roland, P, et al.
(författare)
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A database generator for human brain imaging
- 2001
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Ingår i: TINS - Trends in Neurosciences. - 0166-2236 .- 1878-108X. ; 24:10, s. 562-564
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Tidskriftsartikel (refereegranskat)abstract
- Sharing scientific data containing complex information requires new concepts and new technology. NEUROGENERATOR is a database generator for the neuroimaging community. A database generator is a database that generates new databases. The scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes the data in a uniform way to create databases of homogenous data suitable for data sharing, met-analysis and modelling the human brain at the systems level. These databases are then distributed to the scientists.
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| 5. |
- Bauer, S H J, et al.
(författare)
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A rapid and sensitive procedure for determination of 5-N-acetyl neuraminic acid in lipopolysaccharides of Haemophilus influenzae : a survey of 24 non-typeable H-influenzae strains
- 2001
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Ingår i: Carbohydrate Research. - 0008-6215 .- 1873-426X. ; 335:4, s. 251-260
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Tidskriftsartikel (refereegranskat)abstract
- In view of the importance of 5-N-acetyl neuraminic acid in bacterial pathogenesis, a sensitive, reproducible and reliable method for the determination of 5-N-acetyl neuraminic acid levels in lipopolysaccharide (LPS) is described and applied to 24 different non-typeable Haemophilus influenzae (NTHi) strains. The method involves analysis by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) of terminal 5-N-acetyl neuraminic acid residues released by neuraminidase treatment of O-deacylated LPS. The procedure is relatively fast and the instrumental effort is moderate. The results of the procedure were compared with data obtained by H-1 NMR and electrospray ionisation-mass spectrometry (ESI-MS). The analysis of LPS from 24 NTHi strains showed that 5-N-acetyl neuraminic acid was found to be a common constituent of LPS in NTHi. Only one strain (NTHi 432) did not show any sialylation. Molar ratios (LPS /5-N-acetyl neuraminic acid) ranged between 5/1 and 500/1. Several strains in which no 5-N-acetyl neuraminic acid could be determined by other methods including 1H NMR and ESI-MS were shown to contain 5-N-acetyl neuraminic acid by this HPAEC-PAD procedure. The method was applied to determine levels of terminal 5-N-acetyl neuraminic acid in LPS from NTHi strains grown under different conditions and mutant strains containing inactive LPS biosynthetic genes.
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| 6. |
- Bergman, Jan, et al.
(författare)
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Studies of the reactions between indole-2,3-diones (isatins) and 2-aminobenzylamine
- 2003
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Ingår i: Tetrahedron. - 0040-4020 .- 1464-5416. ; 59:7, s. 1033-1048
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Tidskriftsartikel (refereegranskat)abstract
- Reflux of equimolecular amounts 2-aminobenzylamine and isatins in acetic acid produced indolo[3,2-c]quinolin-6-ones in good yields. A proposed mechanism involving initial formation of a spiro compound is given. This isolable intermediate subsequently rearranges via a sequential isocyanate ring opening and a cyclisation process to a urea derivative which finally cyclized to the indolo[3,2-c]quinolin-6-ones. The urea derivative could be prepared separately and cyclized selectively to indolo[3,2-c]quinolin-6-one. Reaction of N-acetylisatin with 2-aminobenzylamine at room temperature yielded the 1,4-benzodiazepinone 3-(2-acetamidophenyl)-1,5-dihydro-1,4-benzodiazepin-2one whereas its isomer 2(2-acetamidophenyl)-4,5-dihydro-1,4-benzodiazepin-3-one was obtained from 2-(2-acetylaminophenyl)-N-(2-aminobenzyl)-2-oxoacetamide in acetic acid at room temperature. The previously unknown linear isomer of indolo[3,2-c]quinolin-6-one, i.e. indolo[2,3-blquinolin-11-one, has been prepared by thermal (260degreesC) cyclization of methyl 2-phenylamino indole-3-carboxylate, which in turn was prepared in two steps from methyl indole-3-carboxyl ate. (C) 2003 Elsevier Science Ltd. All rights reserved.
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| 7. |
- Büchert, A., et al.
(författare)
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Dioxin contamination in food : Bayreuth, Germany, from September 28 to October 1, 2000
- 2001
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Ingår i: Environmental Science and Pollution Research. - : Ecomed Publishers. - 0944-1344 .- 1614-7499. ; 8:2, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Dioxin and PCB monitoring programs for food and feeding stuff in most countries of the world, including many European Countries are currently inadequate. Better control of food production lines and food processing procedures is needed to minimize entry of dioxin to the food chain and will help to avoid dioxin contamination accidents. This would also improve the ability to trace back a possible contamination to its source. European guidelines for monitoring programs should be established to ensure comparable and meaningful results. These guidelines should define the minimum requirements for the design of monitoring programs, analytical methods, and quality assurance.Though data from Northern Europe shows that the general population exposure to dioxin and PCB has decreased during the last ten years these compounds continue to be a risk of accidental contamination of the food chain. The most prominent recent example is the Belgian dioxin contamination of feeding stuff in 1999. The Belgian dioxin contamination was not detected due to dioxin monitoring programs but by their direct biological effects seen in animals. Four other cases of dioxin contamination have been detected in Europe since 1997 due to local monitoring programs. One of them (citrus pulp pellets 1998) was in a much larger scale than the Belgian dioxin contamination.The general population's exposure to dioxins and PCBs is still in the same range (1-4 pg WHO-TEQ/kg body weight and day) as the recently revised WHO tolerable daily intake (TDI). There is concern that short-term high level exposure to dioxins, furans, and PCB may cause biological effects on the human fetal development and further research is required.Further actions to control sources building on considerable advances already made in many countries may need to be supplemented by measures to prevent direct contamination of feeding stuff or food to reduce general population exposure further.
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| 8. |
- Bäck, Torbjörn, et al.
(författare)
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A TOF-PET system for educational purposes
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 477, s. 82-82
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Tidskriftsartikel (refereegranskat)abstract
- A TOF-PET system has been designed and constructed for educational purposes. The aim of this system is to demonstrate the possibilities of positron emission tomography in general and the time-of-flight method in particular to the students of various courses at the Royal Institute of Technology, Stockholm, Sweden. The set-up consists of 48 small BaF2 crystals coupled to fast photomultipliers placed in a ring geometry. The signals of the photomultipliers are fed into fast constant fraction discriminators (CFD). The outputs of these are directed to a specially designed logic VME unit. which combines the CFD signals of 6 neighbouring channels to one signal by adding a different delay to each channel. The logic circuitry produces a prompt pulse for each event that serves as the start pulse for the 8-channel fast TDC. The delayed pulses act as the stop pulses for the TDC. In a computer. the measured times are converted into information about which the photomultipliers fired with the difference in the time of flight. The set-up is described and the results are presented.
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| 9. |
- Johnson, Ann-Louise, et al.
(författare)
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Synthesis of barettin
- 2004
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 60:4, s. 961-965
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Tidskriftsartikel (refereegranskat)abstract
- The indole alkaloid barettin (with bromine in 6-position), isolated from the marine sponge Geodia Barretti, has been synthesised via a Horner-Wadsworth-Emmons type reaction from 6-bromoindole-3-carboxaldehyde to introduce the dehydro-functionality. Subsequent deprotection and cyclisation afforded the natural product in Z-conformation.
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| 10. |
- Kozlov, Alexander K., et al.
(författare)
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Mechanisms for lateral turns in lamprey in response to descending unilateral commands : a modeling study
- 2002
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Ingår i: Biological Cybernetics. - : Springer Science and Business Media LLC. - 0340-1200 .- 1432-0770. ; 86:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Straight locomotion in the lamprey is, at the segmental level, characterized by alternating bursts of motor activity with equal duration and spike frequency on the left and the right sides of the body. Lateral turns are characterized by three main changes in this pattern: (1) in the turn cycle, the spike frequency, burst duration, and burst proportion (burst duration/cycle duration) increase on the turning side; (2) the cycle duration increases in both the turn cycle and the succeeding cycle; and (3) in the cycle succeeding the turn cycle, the burst duration increases on the non-turning side (rebound). We investigated mechanisms for the generation of turns in single-segment models of the lamprey locomotor spinal network. Activation of crossing inhibitory neurons proved a sufficient mechanism to explain all three changes in the locomotor rhythm during a fictive turn. Increased activation of these cells inhibits the activity of the opposite side during the prolonged burst of the turn cycle, and slows down the locomotor rhythm. Secondly, this activation of the crossing inhibitory neurons is accompanied by an increased calcium influx into the cells. This gives a suppressed activity on the turning side and a contralateral rebound after the turn, through activation of calcium-dependent potassium channels.
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