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- Almstedt, Karin, 1980-, et al.
(författare)
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Unfolding a folding disease: folding, misfolding and aggregation of the marble brain syndrome-associated mutant H107Y of human carbonic anhydrase II
- 2004
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Ingår i: Journal of Molecular Biology. - Oxford : Elsevier. - 0022-2836 .- 1089-8638. ; 342:2, s. 619-633
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Tidskriftsartikel (refereegranskat)abstract
- Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to mutations. The disease marble brain syndrome (MBS), known also as carbonic anhydrase II deficiency syndrome (CADS), can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. One mutation associated with MBS entails the His107Tyr substitution. Here, we demonstrate that this mutation is a remarkably destabilizing folding mutation. The loss-of-function is clearly a folding defect, since the mutant shows 64% of CO2 hydration activity compared to that of the wild-type at low temperature where the mutant is folded. On the contrary, its stability towards thermal and guanidine hydrochloride (GuHCl) denaturation is highly compromised. Using activity assays, CD, fluorescence, NMR, cross-linking, aggregation measurements and molecular modeling, we have mapped the properties of this remarkable mutant. Loss of enzymatic activity had a midpoint temperature of denaturation (Tm) of 16 °C for the mutant compared to 55 °C for the wild-type protein. GuHCl-denaturation (at 4 °C) showed that the native state of the mutant was destabilized by 9.2 kcal/mol. The mutant unfolds through at least two equilibrium intermediates; one novel intermediate that we have termed the molten globule light state and, after further denaturation, the classical molten globule state is populated. Under physiological conditions (neutral pH; 37 °C), the His107Tyr mutant will populate the molten globule light state, likely due to novel interactions between Tyr107 and the surroundings of the critical residue Ser29 that destabilize the native conformation. This intermediate binds the hydrophobic dye 8-anilino-1-naphthalene sulfonic acid (ANS) but not as strong as the molten globule state, and near-UV CD reveals the presence of significant tertiary structure. Notably, this intermediate is not as prone to aggregation as the classical molten globule. As a proof of concept for an intervention strategy with small molecules, we showed that binding of the CA inhibitor acetazolamide increases the stability of the native state of the mutant by 2.9 kcal/mol in accordance with its strong affinity. Acetazolamide shifts the Tm to 34 °C that protects from misfolding and will enable a substantial fraction of the enzyme pool to survive physiological conditions.
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- Adloff, C, et al.
(författare)
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Energy flow and rapidity gaps between jets in photoproduction at HERA
- 2002
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 24:4, s. 517-527
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Tidskriftsartikel (refereegranskat)abstract
- Dijet events in photon-proton collisions in which there is a large pseudorapidity separation, Deltaeta > 2.5 between the two highest E-T jets are studied with the H1 detector at HERA. The inclusive dijet cross sections are measured as functions of the longitudinal momentum fractions of the proton and photon which participate in the production of the jets, x(p)(jets) and x(gamma)(jets) respectively, Deltaeta, the pseudorapidity P separation between the two highest E-T jets, and E-T(gap), the total summed transverse energy between the jets. Rapidity gap events are defined as events in which E-T(gap) is less than E-T(cut), for E-T(cut) varied between jets 0.5 and 2.0 GeV. The fraction of dijet events with a rapidity gap is measured differentially in Deltaeta, x(p)(jets) and x(gamma)(jets). An excess of events with rapidity gaps at low values of E-T(cut) is observed above the expectation from standard photoproduction processes. This excess can be explained by the exchange of a strongly interacting colour singlet object between the jets.
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- Allwood, Carl Martin, et al.
(författare)
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Does mood influence the realism of confidence judgments?
- 2002
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 1467-9450 .- 0036-5564. ; 43:3, s. 253-260
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Tidskriftsartikel (refereegranskat)abstract
- In this study we investigated how mood influences the degree of realism in participants’ confidence judgments (based on an episodic memory task). Using music and film in combination, we successfully induced half of the participants into an elated mood, but failed to induce a sad mood in the other half. Contrary to our prediction, our data indicated that there was no difference in the realism of the confidence between the conditions. When relating this result to previous research our conclusion is that there is no, or very little, influence of mood of moderate intensity on the realism of confidence judgments.
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- Allwood, Carl Martin, et al.
(författare)
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Om betydelsen av elevers metakognitiva förmåga
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This text describes the characteristics of a number of different types of metacognitive judgments relevant for schoolchildren’s studies. It is argued that metacognitive judgments play an important role in children’s learning at school. Moreover, it is also argued many of the modern types of educational approaches, such as the so called ”problem based learning” approach do not have a clear strategy when it comes to the role and training of meta-cognition in the school context.
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- Amberntsson, Annika, 1974, et al.
(författare)
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Investigations of sulphur deactivation of NOx storage catalysts: influence of sulphur carrier and exposure conditions
- 2002
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Ingår i: Catalysis Today. - 0920-5861. ; 73:3-4, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- The influence of SO2, H2S and COS in low concentrations on the deactivation of PURh/BaO/Al2O3 NOx storage catalysts was investigated. Different samples of the catalyst were exposed to synthetic gas mixtures mimicking lean/rich engine cycling in a mixed lean application at 400degreesC. The lean gas mixture contained 8 vol.% O2, 500 vol-ppm C3H6 and 400 vol-ppm NO balanced to 100 vol.% with Ar. The rich excursions were performed by switching off the oxygen supply. Sulphur, 25 vol-ppm of either SO2, H2S or COS, was added to the gas flow either during the lean, the rich or both periods. This procedure aimed at investigating the influence of the exposure conditions and therefore the lean and rich periods were kept equally long (5 min). In addition, thermodynamical calculations for the prevailing conditions were performed.
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