| 1. |
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| 2. |
- Alanärä, Anders, et al.
(författare)
-
Utsättning av djur för jakt och fiske
- 2021
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Bok (populärvet., debatt m.m.)abstract
- SLUs vetenskapliga råd för djurskydd har fått i uppdrag av Jordbruksverket att sammanställa aktuell forskning kring utsättning av djur för jakt och fiske samt att belysa eventuella kunskapsluckor på området. Uppdraget omfattar gräsand, rapphöna, fasan och laxfiskar. Bruket att föda upp fåglar och fiskar för utsättning i syfte att gynna jakt och fiske ifrågasätts inte sällan av etiska skäl, men den diskussionen ligger utanför fokus för denna rapport. Utsättning av fågel och fisk är en antropogen verksamhet som, till skillnad från många andra typer av mänsklig påverkan, syftar till att gynna arterna i fråga. Det kan handla om naturvårdsinsatser, att återinföra försvunna arter eller att på andra sätt berika ekosystemet, inte sällan med ökade möjligheter till jakt eller fiske som slutändamål. Ofta förbereds och åtföljs utsättningar av habitatförbättrande åtgärder som inte endast gynnar de utsatta individerna och deras artfränder, utan även har positiva konsekvenser för biologisk mångfald och ekosystemet i stort. I utarbetandet av regelverket knutet till utsättning av fågel och fisk är det viktigt att även beakta de positiva föresatserna och de konsekvenser som verksamheten kan medföra. Annars riskerar man att engagemang och incitament förloras, till men för biologisk mångfald och en rik och levande landsbygd.
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| 3. |
- Bauer, Mikael, et al.
(författare)
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Zn2+ binding to human calbindin D(28k) and the role of histidine residues.
- 2008
-
Ingår i: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 17:4, s. 760-767
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied the binding of Zn2+ to the hexa EF-hand protein, calbindin D(28k)-a strong Ca2+-binder involved in apoptosis regulation-which is highly expressed in brain tissue. By use of radioblots, isothermal titration calorimetry, and competition with a fluorescent Zn2+ chelator, we find that calbindin D(28k) binds Zn2+ to three rather strong sites with dissociation constants in the low micromolar range. Furthermore, we conclude based on spectroscopic investigations that the Zn2+-bound state is structurally distinct from the Ca2+-bound state and that the two forms are incompatible, yielding negative allosteric interaction between the zinc- and calcium-binding events. ANS titrations reveal a change in hydrophobicity upon binding Zn2+. The binding of Zn2+ is compatible with the ability of calbindin to activate myo-inositol monophosphatase, one of the known targets of calbindin. Through site-directed mutagenesis, we address the role of cysteine and histidine residues in the binding of Zn2+. Mutation of all five cysteines into serines has no effect on Zn2+-binding affinity or stoichiometry. However, mutating histidine 80 into a glutamine reduces the binding affinity of the strongest Zn2+ site, indicating that this residue is involved in coordinating the Zn2+ ion in this site. Mutating histidines 5, 22, or 114 has significantly smaller effects on Zn2+-binding affinity.
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| 4. |
- Berggård, Tord, et al.
(författare)
-
Calbindin D28k exhibits properties characteristic of a Ca2+ sensor.
- 2002
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:19, s. 16662-16672
-
Tidskriftsartikel (refereegranskat)abstract
- Calbindin D28k is a member of the calmodulin super-family of Ca2+ -binding proteins and contains six EF-hands. The protein is generally believed to function as a Ca2+ buffer, but the studies presented in this work indicate that it may also act as a Ca2+ sensor. The results show that Mg2+ binds to the same sites as Ca2+ with an association constant of approximately 1.4 x 10(3) M-1 in 0.15 M KCl. The four high-affinity sites in calbindin D28k bind Ca2+ in a non-sequential, parallel manner. In the presence of physiological concentrations of Mg2+, the Ca2+ -affinity is reduced by a factor of two and the cooperativity, which otherwise is modest, increases. Based on the binding constants determined in the presence of physiological salt concentrations, we estimate that at the Ca2+ concentration in a resting cell calbindin D28k is saturated to 40-75% with Mg2+, but to less than 9 % with Ca2+. In contrast, the protein is expected to be nearly fully saturated with Ca2+ at the Ca2+ level of an activated cell. A substantial conformational change is observed upon Ca2+ binding, but only minor structural changes take place upon Mg2+-binding. This suggests that calbindin D28k undergoes Ca2+ -induced structural changes upon Ca2+ activation of a cell. Thus, calbindin D28k displays several properties that would be expected for a protein involved in Ca2+ -induced signal transmission and hence may function not only as a Ca2+ buffer, but also as a Ca2+ sensor. Digestion patterns resulting from limited proteolysis of the protein suggest that the loop of EF-hand 2, a variant site that does not bind Ca2+, becomes exposed upon Ca2+ binding.
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| 5. |
- Berggård, Tord, et al.
(författare)
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myo-Inositol monophosphatase is an activated target of calbindin D28k.
- 2002
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:44, s. 41954-41959
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Tidskriftsartikel (refereegranskat)abstract
- Calbindin D28k (calbindin) is a member of the calmodulin superfamily of Ca2+ -binding proteins. An intracellular target of calbindin was discovered using bacteriophage display. Human recombinant calbindin was immobilized on magnetic beads and used in affinity purification of phage-displayed peptides from a random 12-mer peptide library. One sequence, SYSSIAKYPSHS, was strongly selected both in the presence of Mg2+ and in the presence of Ca2+. Homology search against the protein sequence data base identified a closely similar sequence, ISSIKEKYPSHS, at residues 55-66 in myo-inositol-1(or 4)-monophosphatase (IMPase, EC 3.1.3.25), which constitute a strongly conserved, and exposed region in the 3D structure. IMPase is a key enzyme in the regulation of the activity of the phosphatidyl inositol signaling pathway. It catalyzes the hydrolysis of myo-inositol-1(or 4)-monophosphate to form free myo-inositol, maintaining a supply that represents the precursor for inositol phospholipid second messenger signaling systems. Fluorescence spectroscopy showed that isolated calbindin and IMPase interact with an apparent equilibrium dissociation constant, KD, of 0.9 mM. Both apo and Ca2+-bound calbindin was found to activate IMPase up to 250-fold, depending on the pH and substrate concentration. The activation is most pronounced at conditions which otherwise lead to a very low activity of IMPase, i.e. at reduced pH and at low substrate concentration.
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| 6. |
- Cabaleiro-Lago, Celia, et al.
(författare)
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Inhibition of Amyloid beta Protein Fibrillation by Polymeric Nanoparticles
- 2008
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 130:46, s. 15437-15443
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Tidskriftsartikel (refereegranskat)abstract
- Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (A beta). We found that these nanoparticles affect mainly the nucleation step of A beta fibrillation. The elongation step is largely unaffected by the particles, and once the M is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of A beta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that A beta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric A beta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of A beta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.
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| 7. |
- Cedervall, Tommy, et al.
(författare)
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Redox sensitive cysteine residues in calbindin D(28)k are structurally and functionally important
- 2005
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 44:2, s. 684-693
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Tidskriftsartikel (refereegranskat)abstract
- Human calbindin D-28k is a Ca2+ binding protein that has been implicated in the protection of cells against apoptosis. In this study, the structural and functional significance of the five cysteine residues present in this protein have been investigated through a series of cystein e-to-serine mutations. The mutants were studied under relevant physiological redox potentials in which conformational changes were monitored using ANS binding. Urea-induced denaturations, as monitored by intrinsic tryptophan fluorescence, were also carried out to compare their relative stability. It was shown that the two N-terminal cysteine residues undergo a redox-driven structural change consistent with disulfide bond formation. The other cysteine residues are not by themselves sufficient at inducing structural change, but they accentuate the disulfide-dependent conformational change in a redox-dependent manner. Mass spectrometry data show that the three C-terminal cysteine residues can be modified by glutathione. Furthermore, under oxidizing conditions, the data display additional species consistent with the conversion of cysteine thiols to sulfenic acids and disulfides to disulfide-S-monoxides. The biological function of calbindin D-28k appears to be tied to the redox state of the cysteine residues. The two N-terminal cysteine residues are required for activation of myo-inositol monophosphatase, and enzyme activation is enhanced under conditions in which these residues are oxidized. Last, oxidized calbindin D-28k binds Ca2+ with lower affinity than does the reduced protein.
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| 8. |
- Cedervall, Tommy, et al.
(författare)
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Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles
- 2007
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 104:7, s. 2050-2055
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Tidskriftsartikel (refereegranskat)abstract
- Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.
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| 9. |
- Cukalevski, Risto, et al.
(författare)
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Role of Aromatic Side Chains in Amyloid β-Protein Aggregation.
- 2012
-
Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 3:12, s. 1008-1016
-
Tidskriftsartikel (refereegranskat)abstract
- Aggregation of the amyloid β-protein (Aβ) is believed to be involved in Alzheimer's disease pathogenesis. Here we have investigated the importance of the aromatic rings at positions 19 and 20 for the aggregation rate and mechanism by substituting phenylalanine with leucine. Aggregation kinetics were monitored as a function of time and peptide concentration by thioflavin T (ThT) fluorescence, the aggregation equilibrium by sedimentation assay, structural changes using circular dichroism spectroscopy and the presence of fibrillar material was detected with cryo-transmission electron microscopy. All peptides convert from monomer to amyloid fibrils in a concentration-dependent manner. Substituting F19 with leucine results in a peptide that aggregates significantly slower than the wild type, while substitution of F20 produces a peptide that aggregates faster. The effects of the two substitutions are additive, since simultaneous substitution of F19 and F20 produces a peptide with aggregation kinetics intermediate between F19L and F20L. Our results suggest that the aromatic side-chain of F19 favors nucleation of the aggregation process and may be an important target for therapeutic intervention.
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| 10. |
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| 11. |
- Dell'Orco, D, et al.
(författare)
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Electrostatic contributions to the kinetics and thermodynamics of protein assembly
- 2005
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 88:3, s. 1991-2002
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Tidskriftsartikel (refereegranskat)abstract
- The role of electrostatic interactions in the assembly of a native protein structure was studied using fragment complementation. Contributions of salt, pH, or surface charges to the kinetics and equilibrium of calbindin D-9k reconstitution was measured in the presence of Ca2+ using surface plasmon resonance and isothermal titration calorimetry. Whereas surface charge substitutions primarily affect the dissociation rate constant, the association rates are correlated with subdomain net charge in a way expected for Coulomb interactions. The affinity is reduced in all mutants, with the largest effect (260-fold) observed for the double mutant K25E+K29E. At low net charge, detailed charge distribution is important, and charges remote from the partner EF-hand have less influence than close ones. The effects of salt and pH on the reconstitution are smaller than mutational effects. The interaction between the wild-type EF-hands occurs with high affinity (K-A = 1.3 x 10(10) M-1; K-D = 80 pM). The enthalpy of association is overall favorable and there appears to be a very large favorable entropic contribution from the desolvation of hydrophobic surfaces that become buried in the complex. Electrostatic interactions contribute significantly to the affinity between the subdomains, but other factors, such as hydrophobic interactions, dominate.
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| 12. |
- Drakenberg, Torbjörn, et al.
(författare)
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Solution Structure of the Ca(2+)-Binding EGF3-4 Pair from Vitamin K-Dependent Protein S: Identification of an Unusual Fold in EGF3(,).
- 2005
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 44:24, s. 8782-8789
-
Tidskriftsartikel (refereegranskat)abstract
- Vitamin K-dependent protein S is a cofactor of activated protein C, a serine protease that regulates blood coagulation. Deficiency of protein S can cause venous thrombosis. Protein S has four EGF domains in tandem; domains 2-4 bind calcium with high affinity whereas domains 1-2 mediate interaction with activated protein C. We have now solved the solution structure of the EGF3-4 fragment of protein S. The linker between the two domains is similar to what has been observed in other calcium-binding EGF domains where it provides an extended conformation. Interestingly, a disagreement between NOE and RDC data revealed a conformational heterogeneity within EGF3 due to a hinge-like motion around Glu186 in the Cys-Glu-Cys sequence, the only point in the domain where flexibility is allowed. The dominant, bent conformation of EGF3 in the pair has no precedent among calcium-binding EGF domains. It is characterized by a change in the angle of Glu186 from 160 ± 40, as seen in ten other EGF domains, to 0 ± 15. NOESY data suggest that Tyr193, a residue not conserved in other calcium-binding EGF domains (except in the homologue Gas6), induces the unique fold of EGF3. However, SAXS data, obtained on EGF1-4 and EGF2-4, showed a dominant, extended conformation in these fragments. This may be due to a counterproductive domain-domain interaction between EGF2 and EGF4 if EGF3 is in a bent conformation. We speculate that the ability of EGF3 to adopt different conformations may be of functional significance in protein-protein interactions involving protein S.
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| 13. |
- Elldér, Erik, et al.
(författare)
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Is a car necessary for active aging? Relationships between aging, car use, and time spent on activities that sustain health and well-being
- 2023
-
Ingår i: Transportation Research Interdisciplinary Perspectives. - 2590-1982 .- 2590-1982. ; 22
-
Tidskriftsartikel (refereegranskat)abstract
- The aging population of the Global North is increasingly car dependent, with repercussions for health and well-being. This article analyzes how car use interacts with living an active life and how this has changed over time in Sweden. National time use data were used to analyze change in two cross sections of older people (65–84 years old) over a ten-year period (2000/01–2010/11). Previous studies concentrated on the relationship between travel behavior as such and older adult’s access to driver’s licenses and cars. We offer an integrated approach that includes all daily activities as we explore the changing social distribution of car use, as well as how different levels of car use are associated with time spent on active aging activities that benefit individuals and society. We conclude that an increasing proportion of the older population in Sweden are moderate to heavy car users and identify convergence over time between car use by older women and older men. We also find that heavy car users spend more time traveling to active aging activities. At first glance, this finding suggest that older people in Sweden are dependent on a car for living an active life. However, examination of how much time is actually spent on active activities after travel time is excluded reveals that few significant differences remain. This nuances the idea that access to a car is a necessity for spending time in activities that contribute to society and to personal well-being in old age.
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| 14. |
- Evenäs, Johan, et al.
(författare)
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Ca2+ binding and conformational changes in a calmodulin domain
- 1998
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 37:39, s. 13744-13754
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium activation of the C-terminal domain of calmodulin was studied using 1H and 15N NMR spectroscopy. The important role played by the conserved bidentate glutmate Ca2+ ligand in the binding loops is emphasized by the striking effects resulting from a mutation of this glutantic acid to a glutamine, i.e. E104Q in loop III and E140Q in loop IV. The study involves determination of Ca2+ binding constants, assignments, and structural characterizations of the apo, (Ca2+)1, and (Ca2+)2 states of the E104Q mutant and comparisons to the wild-type protein and the E140Q mutant [Evenas et al. (1997) Biochemistry 36, 3448-3457]. NMR titration data show sequential Ca2+ binding in the E104Q mutant. The first Ca2+ binds to loop IV and the second to loop III, which is the order reverse to that observed for the E140Q mutant. In both mutants, the major structural changes occur upon Ca2+ binding to loop IV, which implies a different response to Ca2+ binding in the N- and C-terminal EF-hands. Spectral characteristics show that the (Ca2+)1 and (Ca2+)2 states of the E104Q mutant undergo global exchange on a 10-100 μs time scale between conformations seemingly similar to the closed and open structures of this domain in wild-type calmodulin, paralleling earlier observations for the (Ca2+)2 state of the E140Q mutant, indicating that both glutamic acid residues, E104 and E140, are required for stabilization of the open conformation in the (Ca2+)2 state. To verify that the NOE constraints cannot be fulfilled in a single structure, solution structures of the (Ca2+)2 state of the E104Q mutant are calculated. Within the ensemble of structures the precision is good. However, the clearly dynamic nature of the state, a large number of violated distance restraints, ill-defined secondary structural elements, and comparisons to the structures of calmodulin indicate that the ensemble does not provide a good picture of the (Ca2+)2 state of the E104Q mutant but rather represents the distance- averaged structure of at least two distinct different conformations.
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| 15. |
- Evenäs, Johan, et al.
(författare)
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NMR studies of the E140Q mutant of the carboxy-terminal domain of calmodulin reveal global conformational exchange in the Ca2+-saturated state
- 1997
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 36:12, s. 3448-3457
-
Tidskriftsartikel (refereegranskat)abstract
- In the present investigation, the Ca2+ activation of the C-terminal domain of bovine calmodulin and the effects of replacing the bidentate Ca2+-coordinating glutamic acid residue in the 12th and last position of loop IV with a glutamine are studied by NMR spectroscopy. The mutation E140Q results in sequential Ca2+ binding in this domain and has far-reaching effects on the structure of (Ca2+)2 TR2C, thereby providing further evidence for the critical role of this glutamic acid residue for the Ca2+- induced conformational change of regulatory EF-hand proteins. Analyses of the NOESY spectra of the mutant under Ca2+-saturated conditions, such that 97% of the protein is in the (Ca2+)2 form, revealed two sets of mutually exclusive NOEs. One set of NOEs is found to be consistent with the closed structure observed in the apo state of the C-terminal domain of the wild- type protein, while the other set supports the open structure observed in the Ca2+-saturated state. In addition, several residues in the hydrophobic core exhibit broadened resonances. We conclude that the (Ca2+)2 form of the mutant experiences a global conformational exchange between states similar to the closed and open conformations of the C-terminal domain of wild-type calmodulin. A population of 65 ± 15% of the open conformation and an exchange rate of (1-7) x 104 s-1 were estimated from the NMR data and the chemical shifts of the wild-type protein. From a Ca2- titration of the 15N-labeled mutant, the macroscopic binding constants (log(K1) = 4.9 ± 0.3 and log(K2) = 3.15 ± 0.10] and the inherent chemical shifts of the intermediate (Ca2+)1 form of the mutant were determined using NMR. Valuable information was also provided on the mechanism of the Ca2+ activation and the roles of the structural elements in the two Ca2+- binding events. Comparison with the wild-type protein indicates that the (Ca2+)1 conformation of the mutant is essentially closed but that some rearrangement of the empty loop IV toward the Ca2+-bound form has occurred.
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| 16. |
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| 17. |
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| 18. |
- Fahlén, Daniel, et al.
(författare)
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Vad gör man när man reser? Hur människor använder sin restid i regional kollektivtrafik
- 2010
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Ingår i: Transportforum, 13-14 januari 2010, Linköping.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Här presenteras resultat från en undersökning av hur människors faktiskt använder sin restid när de reser med kollektiva färdmedel. Tre konkreta frågeställningar vägleder: i) vilka aktiviteter ägnar man sig åt under resan, ii) vilken utrustning har man tillgång och använder, samt iii) hur värderas tiden ombord av resenärerna. Enkätundersökning omfattar 400 resenärer och fokuserar regionala resor med buss och tåg i Västra Götaland
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| 19. |
- Frändberg, Lotta, 1964, et al.
(författare)
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Aspects of Corporeal, Virtual and Media Mobility Development in Sweden
- 2008
-
Ingår i: Cosmobilities workshop: The future of Cosmobilities Network, 12-14 march 2008, Holbaek, Denmark.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Diverse forms of spatial mobility are significant features of current social life. The rapid and converging development of space-transcending technologies (high-speed transportation and information and communication technologies) and still increasing virtual access to other places through media representation (e.g. news and popular culture) are thoroughly affecting people’s use of space and place. Decreased friction of distance, extended social networks and everyday activity patterns are major indicators of this. Gradually, spatial mobility is becoming institutionalised and expected, turning high levels of travel and communication from a choice to more of a necessity. Our projects aim to explore the development of various forms of spatial mobility and human interaction, be they physical, virtual, or media related. Their intricate interrelations in terms of complements, substitutes, displacements, and modifications − and the intersections between these − are a particular focus.
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| 20. |
- Frändberg, Lotta, 1964, et al.
(författare)
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Integrated Mobility Research
- 2004
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Ingår i: Poster at the International Geographical Union’s congress, Glasgow 15-20 August 2004.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 21. |
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| 22. |
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| 23. |
- Gil Sola, Ana, et al.
(författare)
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Närhetens roll för människors livsprojekt och genuspräglade vardagsliv i staden
- 2024
-
Ingår i: Sammanställning av referat från Transportforum 2024. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 195-196
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Vår studie belyser närhetens roll i människors vardag, olika överordnade ambitioner och syften bakom människors användning av närområdet, i vilka vardagssituationer närhet är avgörande, och för vilka syften långväga rörlighet är det lämpligaste sättet att få tillgång till aktiviteter i vardagen. Studien bygger på 20 djupintervjuer genomförda i två områden i Göteborg: Frölunda och Kvillebäcken. För att förstå hur hushåll organiserar sin vardag i samklang med olika övergripande mål, tar vi stöd i begreppet livsprojekt. Vi lånar begreppet projekt från tidsgeografin, där det används för att beskriva de rutiner en människa upprätthåller i relation till vissa överordnade mål i livet. De innefattar således flera aktiviteter vilka utförs med ett gemensamt syfte, exempelvis att ta hand om sina barn eller att försörja sig.Intervjustudierna visar att närområdet kan spela flera olika roller i människors liv, samtidigt som det på olikartade sätt integreras i vardagslivet. Respondenterna eftersträvar flera livsprojekt samtidigt, och dessa uppfylls ibland parallellt genom olika aktiviteter. Från våra studier kan vi tydliggöra fem livsprojekt där närhet har en avgörande betydelse: att ha ett flexibelt vardagsliv, att leva ett självständigt liv, att vara socialt förankrad, att ha okomplicerad rekreation i vardagen, samt att ha en miljömässigt hållbar livsföring. Hur viktiga dessa livsprojekt är i människors liv varierar från individ till individ och beror bland annat på kön och i vilken livsfas man befinner sig i.En slutsats är att avstånd och skala spelar en tydlig roll för hur olika livsprojekt kan uppfyllas, liksom att alla människors livsprojekt inte understödjs av närområdet. Förtätning av områden som är viktiga för människors lokala livsprojekt bör ske med stor omsorg för dessa. Risken är annars att förutsättningar för de lokala livsprojekten försämras: att grönområden byggs bort, platsens identitet förändras, gentrifiering sker med krav på flyttningar, liksom förlust av lugna miljöer för rekreation, social samvaro och trygga förflyttningar (på grund av ökad trafik och minskad vegetation och naturmiljöer).
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| 24. |
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| 25. |
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| 26. |
- Goscinski, Gunilla, et al.
(författare)
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Release of SpeA from Streptococcus pyogenes after exposure to penicillin : dependency on dose and inhibition by clindamycin
- 2006
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:11-12, s. 983-987
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Tidskriftsartikel (refereegranskat)abstract
- The amount and time course of SpeA release from group A streptococci (GAS) was studied at different starting inoculae after exposure to different doses of penicillin, clindamycin or a combination of the 2. The release was related to the bacterial concentration and killing rate. A clinical GAS strain was exposed to benzylpenicillin, 2 and 1000 × MIC, clindamycin, 2 and 32 × MIC, or combinations of the 2. Samples for viable counts and SpeA analyses were drawn before and after the addition of antibiotics and at 3, 6 and 24 h. The SpeA release was higher at low than at high concentrations of penicillin and the combination (both, p < 0.05). The addition of clindamycin to penicillin reduced SpeA production at both concentrations (p < 0.01). Most SpeA was released before 3 h, and for penicillin and the combination, the amount correlated to the number of killed bacteria during this period (r = 0.50; p < 0.05). A positive correlation was found between the inoculum size and the SpeA concentration at time zero (r = 0.54; p < 0.05). The SpeA concentration was dependent on the initial number of bacteria, the class of antibiotic, the dose of penicillin and the killing rate.
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| 27. |
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| 28. |
- Halbhuber, Z, et al.
(författare)
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Overexpression and purification of recombinant membrane PsbH protein in Escherichia coli.
- 2003
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Ingår i: Protein Expression and Purification. - 1046-5928. ; 32:1, s. 18-27
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we featured an expression system that enables the production of sufficient quantities (~mg) of low molecular weight membrane protein of photosystem II, PsbH protein, for solid-state NMR as well as other biophysical studies. PsbH gene from cyanobacterium Synechocystis sp. PCC 6803 was cloned into a plasmid expression vector, which allowed expression of the PsbH protein as a glutathione-S transferase (GST) fusion protein in Escherichia coli BL21(DE3) cells. A relatively large GST anchor overcomes foreseeable problems with the low solubility of membrane proteins and the toxicity caused by protein incorporation into the membrane of the host organism. As a result, the majority of fusion protein was obtained in a soluble state and could be purified from crude bacterial lysate by affinity chromatography on immobilized glutathione under non-denaturing conditions. The PsbH protein was cleaved from the carrier protein with Factor Xa protease and purified on DEAE–cellulose column with yields of up to 2.1 g protein/ml of bacterial culture. The procedure as we optimized is applicable for isolation of small membrane proteins for structural studies.
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| 29. |
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| 30. |
- Hellstrand, Erik, et al.
(författare)
-
Förster resonance energy transfer studies of calmodulin produced by native protein ligation reveal inter-domain electrostatic repulsion.
- 2013
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; 280:11, s. 2675-2687
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores the influence of long-range intra-protein electrostatic interactions on the conformation of calmodulin in solution. Ensemble Förster resonance energy transfer (FRET) is measured for calmodulin with a fluorophore pair incorporated specifically with a donor at residue 17 and an acceptor at position 117. This construct was generated by a combination of solid phase peptide synthesis, cloning, expression and native chemical ligation. This labelling method has not previously been used with calmodulin and represents a convenient method for ensuring the explicit positioning of the fluorophores. The ensemble FRET experiments reveal significant electrostatic repulsion between the globular domains in the calcium-free protein. At low salt, calmodulin has a relatively extended conformation and the distance between the domains is further increased by denaturation, by heat or by non-ionic denaturants. The repulsion between domains is screened by salt and is also diminished by calcium binding, which changes the protein net charge from -23 to -15. Compared with the calcium-free form at low salt, the FRET efficiency for the calcium-bound form has, on average, increased 10-fold. The conformation of the calcium form is insensitive to salt screening. These results imply that when the two globular domains of calmodulin interact with target, there is no significant free energy penalty due to electrostatic interactions.
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| 31. |
- Hong, Eva, et al.
(författare)
-
Target Gene Sequencing To Define the Susceptibility of Neisseria meningitidis to Ciprofloxacin
- 2013
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 57:4, s. 1961-1964
-
Tidskriftsartikel (refereegranskat)abstract
- Meningococcal gyrA gene sequence data, MICs, and mouse infection were used to define the ciprofloxacin breakpoint for Neisseria meningitidis. Residue T91 or D95 of GyrA was altered in all meningococcal isolates with MICs of >= 0.064 mu g/ml but not among isolates with MICs of <= 0.032 mu g/ml. Experimental infection of ciprofloxacin-treated mice showed slower bacterial clearance when GyrA was altered. These data suggest a MIC of >= 0.064 mu g/ml as the ciprofloxacin breakpoint for meningococci and argue for the molecular detection of ciprofloxacin resistance.
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| 32. |
- Hysing, Eva-Britt, et al.
(författare)
-
Detection of systemic inflammation in severely impaired chronic pain patients and effects of a multimodal pain rehabilitation program
- 2019
-
Ingår i: Scandinavian Journal of Pain. - : WALTER DE GRUYTER GMBH. - 1877-8860 .- 1877-8879. ; 19:2, s. 235-244
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Recent research indicates a previously unknown low-grade systemic or neurogenic inflammation in groups of chronic pain (CP) patients. Low-grade inflammation may have an important role in symptoms that have previously not been well depicted: widespread pain, tiredness and cognitive dysfunctions frequently seen in severely impaired CP patients. This study aimed to investigate the plasma inflammatory profile in a group of very complex CP patients at baseline and at a 1-year follow-up after participation in a cognitive behavior therapy (CBT)-based multimodal pain rehabilitation program (PRP).Methods: Blood samples were collected from 52 well-characterized CP patients. Age- and sex-matched healthy blood donors served as controls. The samples were analyzed with a multiple Proximal Extension Analysis allowing a simultaneous analysis of 92 inflammation-related proteins consisting mainly of cytokines, chemokines and growth-factors. At follow-up, 1-year after participation in the RPR samples from 28 patients were analyzed. The results were confirmed by a multi-array technology that allows quantitative estimation.Results: Clear signs of increased inflammatory activity were detected in the CP patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43/92 inflammatory biomarkers compared with the controls. In three biomarkers (CXCL5, SIRT2, AXIN1) the expression levels were elevated more than eight times. One year after the PRP, with the patients serving as their own controls, a significant decrease in overall inflammatory activity was found.Conclusions: Our results indicate that the most impaired CP patients suffer from low-grade chronic systemic inflammation not described earlier with this level of detail. The results may have implications for a better understanding of the cluster of co-morbid symptoms described as the "sickness-syndrome" and the wide-spread pain seen in this group of patients. The decrease in inflammatory biomarkers noted at the follow-up after participation in the PRP may reflect the positive effects obtained on somatic and psycho-social mechanisms involved in the inflammatory process by a rehabilitation program. Besides the PRP, no major changes in medication or lifestyle factors were implemented during the same period. To our knowledge, this is the first study reporting that a PRP may induce inflammatory-reducing effects. Further studies are needed to verify the objective findings in CP patients and address the question of causality that remains to be solved.
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| 33. |
- Julenius, Karin, et al.
(författare)
-
Coupling of ligand binding and dimerization of helix-loop-helix peptides: Spectroscopic and sedimentation analyses of calbindin D-9k EF-hands
- 2002
-
Ingår i: Proteins. - : Wiley. - 0887-3585. ; 47:3, s. 323-333
-
Tidskriftsartikel (refereegranskat)abstract
- Isolated Ca2+-binding EF-hand peptides have a tendency to dimerize. This study is an attempt to account for the coupled equilibria of Ca2+-binding and peptide association for two EF-hands with strikingly different loop sequence and net charge. We have studied each of the two separate EF-hand fragments from calbindin D-9k. A series of Ca2+-titrations at different peptide concentrations were monitored by CD and fluorescence spectroscopy. All data were fitted simultaneously to both a complete model of all possible equilibrium intermediates and a reduced model not including dimerization in the absence of Ca2+. Analytical ultracentrifugation shows that the peptides may occur as monomers or dimers depending on the solution conditions. Our results show strikingly different behavior for the two EF-hands. The fragment containing the N-terminal EF-hand shows a strong tendency to dimerize in the Ca2+-bound state. The average Ca2+-affinity is 3.5 orders of magnitude lower than for the intact protein. We observe a large apparent cooperativity of Ca2+ binding for the overall process from Ca2+-free monomer to fully loaded dimer, showing that a Ca2+-free EF-hand folds upon dimerization to a Ca2+-bound EF-hand, thereby presenting a preformed binding site to the second Ca2+-ion. The C-terminal EF-hand shows a much smaller tendency to dimerize, which may be related to its larger net negative charge. In spite of the differences in dimerization behavior, the Ca2+ affinities of both EF-hand fragments are similar and in the range IgK = 4.6-5.3.
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| 34. |
- Lagrell, Ellen, 1983, et al.
(författare)
-
Accessibility strategies beyond the private car: A study of voluntarily carless families with young children in Gothenburg
- 2018
-
Ingår i: Journal of Transport Geography. - : Elsevier BV. - 0966-6923 .- 1873-1236. ; 72:October 2018, s. 218-227
-
Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd It is generally recognized that technological fixes alone cannot solve car-induced sustainability problems requiring measures to reduce car use. However, there is a knowledge gap concerning what we can learn from the experience of people who voluntarily refrain from car ownership. This paper aims to explore how everyday life is organized and perceived by voluntarily carless households with complex travel needs, focusing on dual-income families with children living in an urban setting (Gothenburg, Sweden). Through a time-geographical theoretical lens and drawing on eight in-depth interviews with parents, we scrutinize the accessibility strategies of these families and the perceived implications of being voluntarily carless for daily living. We find that these families use largely proximity-oriented strategies and combine various practices in managing time-pressed everyday life. The findings underscore the situatedness of carlessness and the importance of the inherent constraints and fixities of different everyday life projects. Notably, adaptation is considered to be well functioning in the spheres of mandatory activities and bounded routines (related to work, school, and consumption). Regarding free-time activities, carlessness is associated with more friction and perceived inconvenience. Questions are raised regarding the long-term persistence of voluntary carlessness, as family life situations may change. The results merit further consideration in sustainable transport and land use planning as well as regarding the wider organization of society.
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| 35. |
- Landby, Emma, 1991-
(författare)
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Family, disability and (im)mobility : geographies of families with wheelchair-using children with cerebral palsy
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mobility is important in shaping people’s lives and experiences through places visited and social interactions with other people. In families with children, mobilities are usually complex and include negotiations between various family members, affecting how they move about in time-space. While children in general often are dependent on parental support in relation to transport, children with disabilities tend to be even more reliant on their parents, not least because they are highly car dependent due to social and environmental barriers associated with other transport modes. This implies that not only disabled children, but also other family members, could be affected by disability related mobility constraints. This thesis focuses especially on mobilities of Swedish families with wheelchair-using children with cerebral palsy. Based on interviews, time-use diaries and a survey, I explore how disabling barriers affect families’ daily and tourism mobilities. I use a time-geographical framework, especially focusing on projects and constraints. My findings show that these families experience many constraints on mobilities and numerous negotiations and adaptations need to be done to enable mobility for all family members. Oftentimes, it is the disabled child’s mobility that is prioritised, which in everyday life often is related to an increased number of trips (e.g. appointments with physiotherapists, doctors and other authorities involved in healthcare) as well as longer distances travelled to reach accessible (pre)schools and leisure activities. Parents are often accompanying their children, which limits the time available for the parents’ own mobilities, impinges on their geographical reach and affect their possibilities on the labour market. A solution to improve opportunities for (independent) daily mobility for all family members is to have personal assistance in combination with special transport services for the disabled child, which are part of the Swedish support system. For tourism mobility, families often travel together and disabling barriers affect how and where they can travel. My findings show that these families have a limited set of tourism destinations that they can travel to. Disabling barriers on tourism mobility can be negotiated by leaving the disabled child at home or going on separate trips. This opens up mobility opportunities for the non-disabled family members, but can put further limitations on the mobility of the disabled child.
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| 36. |
- Li, C. J., et al.
(författare)
-
Changes in Everyday Internet Use and Home Activity During and After Pandemic-Related Lockdowns: A Case Study in Shuangjing Subdistrict, Beijing
- 2023
-
Ingår i: Tijdschrift Voor Economische En Sociale Geografie. - : Wiley. - 0040-747X .- 1467-9663. ; 114:2, s. 117-132
-
Tidskriftsartikel (refereegranskat)abstract
- The outbreak of the COVID-19 pandemic affected the everyday lives of people. Recent studies have found that Internet use increased during lockdowns and helped people cope with spatial constraints on daily activity. However, long-term implications on the digitalization of everyday life are still unknown. This study aims to improve the understanding of changes in Internet use during and after lockdown and how these changes relate to home activity and activity context. We draw on a case study of pre-, mid- and post-lockdown periods in Shuangjing Subdistrict, Beijing. We find that Internet use increased during and after the lockdown, indicating a persistent effect. Home activity mediated the increase in Internet use, suggesting that people stayed at home engaging in more Internet use when restrictions were eased. Work activity and family affairs strengthened the positive impact on Internet use during the lockdown. The influence on Internet use differed depending on sociodemographic characteristics.
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| 37. |
- Li, Chunjiang, et al.
(författare)
-
Understanding the Hybridization of Everyday Activities from a Time-Geographic Perspective
- 2023
-
Ingår i: Annals of the American Association of Geographers. - 2469-4452 .- 2469-4460. ; 114:1, s. 185-199
-
Tidskriftsartikel (refereegranskat)abstract
- In contrast to the dichotomous distinction between offline and online activity in much previous research, we argue for hybridization as a key feature of the digitalized postpandemic society, shaping and constraining the everyday lives and activities of individuals in new, unforeseen ways. The current understanding of the complex ways in which hybridization plays out and reorders everyday life is limited, partly due to a lack of relevant conceptualizations and methodological tools. The aim of this article is to further develop the time-geographic approach, as theory and method, to understand and visualize the hybridization of everyday activities. The article contributes to previous literature on everyday life digitalization in several important respects. The notions of hybrid activities, grounds, and sequences are proposed for an enhanced theoretical understanding of hybridization. Moreover, we argue that interrelated hybrid constraints shape the spatiotemporal organization of everyday activities. The concept of pocket of mediated order is proposed as a new domain of everyday activities in the hybrid era, supporting the accomplishment of everyday projects, yetalso transforming the local pockets of order. Finally, drawing on a real family case, we refine the time-geographical notation system to capture and visualize the full complexity of hybridization in the time–space setting of daily life.
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| 38. |
- Lindman, Stina, et al.
(författare)
-
Green fluorescence induced by EF-hand assembly in a split GFP system.
- 2009
-
Ingår i: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 18:6, s. 1221-1229
-
Tidskriftsartikel (refereegranskat)abstract
- The affinity between the 1-157 and 158-238 fragments of green fluorescent protein (GFP) is too low for spontaneous in vivo reassembly of the protein upon co-expression of the two fragments. This prevents chromophore maturation and the cells lack GFP fluorescence. We have utilized the very high affinity between the two EF-hands of calbindin D(9k) to facilitate GFP assembly from its fragments and to introduce a calcium dependent molecular switch. In GFPN-EF1, residues 1-157 of GFP are fused to residues 1-43 of calbindin, and in EF2-GFPC, residues 44-75 of calbindin are fused to residues 158-238 of GFP. When co-expressed, GFPN-EF1 and EF2-GFPC associate spontaneously and rapidly resulting in a folded reconstituted protein with bright GFP fluorescence. The high affinity of GFPN-EF1 for EF2-GFPC leads to brighter fluorescence of the cells compared to cells with a control constructs carrying leucine zippers (Wilson et al., Nature Methods 2004;3:255). The complex of GFPN-EF1 and EF2-GFPC was purified from cells using metal-ion chelate chromatography and the temperature dependence of GFP fluorescence was found to be calcium dependent. The GFPN-EF1 and EF2-GFPC fragments were separated by ion exchange chromatography. The assembly of the fragments was found to be reversible and the complex was regained upon mixing, as evidenced by surface plasmon resonance (SPR) data. The affinity between GFPN-EF1 and EF2-GFPC as well as rates of association and dissociation were found to be Ca(2+)-dependent.
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| 39. |
- Lindman, Stina, et al.
(författare)
-
Systematic investigation of the thermodynamics of HSA adsorption to N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles. Effects of particle size and hydrophobicity
- 2007
-
Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 7:4, s. 914-920
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles in biological fluids almost invariably become coated with proteins that may confer nanomedical and nanotoxicological effects. Understanding these effects requires quantitative measurements using simple systems. Adsorption of HSA to copolymer nanoparticles of varying hydrophobicity and curvature was studied using ITC, yielding stoichiometry, affinity, and enthalpy changes upon binding. The hydrophobicity was controlled via the co-monomer ratio, N-iso-propylacrylamide/N-tert-butylacrylamide. The most hydrophobic particles become fully covered with a single layer of protein, except at high curvature.
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| 40. |
- Linse, Sara, et al.
(författare)
-
Benefits and constrains of covalency : the role of loop length in protein stability and ligand binding
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Protein folding is governed by non-covalent interactions under the benefits and constraints of the covalent linkage of the backbone chain. In the current work we investigate the influence of loop length variation on the free energies of folding and ligand binding in a small globular single-domain protein containing two EF-hand subdomains—calbindin D9k. We introduce a linker extension between the subdomains and vary its length between 1 to 16 glycine residues. We find a close to linear relationship between the linker length and the free energy of folding of the Ca2+-free protein. In contrast, the linker length has only a marginal effect on the Ca2+ affinity and cooperativity. The variant with a single-glycine extension displays slightly increased Ca2+ affinity, suggesting that the slightly extended linker allows optimized packing of the Ca2+-bound state. For the extreme case of disconnected subdomains, Ca2+ binding becomes coupled to folding and assembly. Still, a high affinity between the EF-hands causes the non-covalent pair to retain a relatively high apparent Ca2+ affinity. Our results imply that loop length variation could be an evolutionary option for modulating properties such as protein stability and turnover without compromising the energetics of the specific function of the protein.
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| 41. |
- Linse, Sara, et al.
(författare)
-
Nucleation of protein fibrillation by nanoparticles
- 2007
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 104:21, s. 8691-8696
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles present enormous surface areas and are found to enhance the rate of protein fibrillation by decreasing the lag time for nucleation. Protein fibrillation is involved in many human diseases, including Alzheimer's, Creutzfeld-Jacob disease, and dialysis-related amyloidosis. Fibril formation occurs by nucleation-dependent kinetics, wherein formation of a critical nucleus is the key rate-determining step, after which fibrillation proceeds rapidly. We show that nanoparticles (copolymer particles, cerium oxide particles, quantum dots, and carbon nanotubes) enhance the probability of appearance of a critical nucleus for nucleation of protein fibrils from human beta(2)-microglobulin. The observed shorter lag (nucleation) phase depends on the amount and nature of particle surface. There is an exchange of protein between solution and nanoparticle surface, and beta(2)-Microglobulin forms multiple layers on the particle surface, providing a locally increased protein concentration promoting oligomer formation. This and the shortened lag phase suggest a mechanism involving surf ace-assisted nucleation that may increase the risk for toxic cluster and amyloid formation. It also opens the door to new routes for the controlled self-assembly of proteins and peptides into novel nanomaterials.
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| 42. |
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| 43. |
- Nelson, MR, et al.
(författare)
-
The EF-hand domain: A globally cooperative structural unit
- 2002
-
Ingår i: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 11:2, s. 198-205
-
Tidskriftsartikel (refereegranskat)abstract
- EF-hand Ca2+-binding proteins participate in both modulation of Ca2+ signals and direct transduction of the ionic signal into downstream biochemical events. The range of biochemical. functions of these proteins is correlated with differences in the way in which they respond to the binding of Ca2+. The EF-hand domains of calbindin D-9k and calmodulin are homologous, yet they respond to the binding of calcium ions in a drastically different manner. A series of comparative analyses of their structures enabled the development of hypotheses about which residues in these proteins control the calcium-induced changes in conformation. To test our understanding of the relationship between protein sequence and structure, we specifically designed the F36G mutation of the EF-hand protein calbindin D-9k to alter the packing of helices I and II in the apoprotein. The three-dimensional structure of apo F36G was determined in solution by nuclear magnetic resonance spectroscopy and showed that the design was successful. Surprisingly, significant structural perturbations also were found to extend far from the site of mutation. The observation of such long-range effects provides clear evidence that four-helix EF-hand domains should be treated as a single globally cooperative unit. A hypothetical mechanism for how the long-range effects are transmitted is described. Our results support the concept of energetic and structural coupling of the key residues that are crucial for a protein's fold and function.
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| 44. |
- Oktaviani, Nur Alia, et al.
(författare)
-
100% complete assignment of non-labile H-1, C-13, and N-15 signals for calcium-loaded calbindin D-9k P43G
- 2011
-
Ingår i: Biomolecular NMR Assignments. - : Springer Science and Business Media LLC. - 1874-2718 .- 1874-270X. ; 5:1, s. 79-84
-
Tidskriftsartikel (refereegranskat)abstract
- Here we present the 100% complete assignment chemical shift of non-labile H-1, N-15 and C-13 nuclei of Calbindin D-9k P43G. The assignment includes all non-exchangeable side chain nuclei, including ones that are rarely reported, such as LysN zeta as well as the termini. NMR experiments required to achieve truly complete assignments are discussed. To the best of our knowledge our assignments for Calbindin D-9k extend beyond previous studies reaching near-completeness (Vis et al. in Biochem 33:14858-14870, 1994; Yamazaki et al. in J Am Chem Soc 116:6464-6465, 1994; Yamazaki et al. in Biochem 32:5656-5669, 1993b).
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| 45. |
- Serlachius, Eva, et al.
(författare)
-
Ångeststörningar hos barn och ungdomar - hjälp finns att få
- 2012
-
Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 109:43-44, s. 1946-1949
-
Tidskriftsartikel (refereegranskat)abstract
- Uppskattningsvis har cirka 5–10 procent av alla barn och ungdomar någon form av ångeststörning, vilket innebär att det är en av de vanligaste psykiska störningarna hos barn och ungdomar.Ångeststörningar debuterar ofta i barn- eller ungdomsåren och har ett relativt kroniskt förlopp om de förblir obehandlade.Kognitiv beteendeterapi (KBT) och antidepressiva läkemedel har i studier visat sig vara effektiv behandlingar, och KBT rekommenderas i första hand.Även om vi i dag har evidensbaserad behandling för barn och ungdomar med ångeststörningar finns stora kunskapsluckor, och behovet av behandlingsstudier är stort.
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| 46. |
- Szczepankiewicz, Olga, et al.
(författare)
-
Interactions in the native state of monellin, which play a protective role against aggregation.
- 2011
-
Ingår i: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-2051. ; 7, s. 521-532
-
Tidskriftsartikel (refereegranskat)abstract
- A series of recent studies have provided initial evidence about the role of specific intra-molecular interactions in maintaining proteins in their soluble state and in protecting them from aggregation. Here we show that the amino acid sequence of the protein monellin contains two aggregation-prone regions that are prevented from initiating aggregation by multiple non-covalent interactions that favor their burial within the folded state of the protein. By investigating the behavior of single-chain monellin and a series of five of its mutational variants using a variety of biochemical, biophysical and computational techniques, we found that weakening of the non-covalent interaction that stabilizes the native state of the protein leads to an enhanced aggregation propensity. The lag time for fibrillation was found to correlate with the apparent midpoint of thermal denaturation for the series of mutational variants, thus showing that a reduced thermal stability is associated with an increased aggregation tendency. We rationalize these findings by showing that the increase in the aggregation propensity upon mutation can be predicted in a quantitative manner through the increase in the exposure to solvent of the amyloidogenic regions of the sequence caused by the destabilization of the native state. Our findings, which are further discussed in terms of the structure of monellin and the perturbation by the amino acid substitutions of the contact surface between the two subdomains that compose the folded state of monellin, provide a detailed description of the specific intra-molecular interactions that prevent aggregation by stabilizing the native state of a protein.
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| 47. |
- Szczepankiewicz, Olga, et al.
(författare)
-
N-Terminal Extensions Retard Aβ42 Fibril Formation but Allow Cross-Seeding and Coaggregation with Aβ42.
- 2015
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 137:46, s. 14673-14685
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid β-protein (Aβ) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the aggregation process. Until recently, naturally occurring amyloid β-protein (Aβ) variants were believed to begin at or after the canonical β-secretase cleavage site within the amyloid β-protein precursor. However, N-terminally extended forms of Aβ (NTE-Aβ) were recently discovered and may contribute to Alzheimer's disease. Here, we have used thioflavin T fluorescence to study the aggregation kinetics of Aβ42 variants with N-terminal extensions of 5-40 residues, and transmission electron microscopy to analyze the end states. We find that all variants form amyloid fibrils of similar morphology as Aβ42, but the half-time of aggregation (t1/2) increases exponentially with extension length. Monte Carlo simulations of model peptides suggest that the retardation is due to an underlying general physicochemical effect involving reduced frequency of productive molecular encounters. Indeed, global kinetic analyses reveal that NTE-Aβ42s form fibrils via the same mechanism as Aβ42, but all microscopic rate constants (primary and secondary nucleation, elongation) are reduced for the N-terminally extended variants. Still, Aβ42 and NTE-Aβ42 coaggregate to form mixed fibrils and fibrils of either Aβ42 or NTE-Aβ42 catalyze aggregation of all monomers. NTE-Aβ42 monomers display reduced aggregation rate with all kinds of seeds implying that extended termini interfere with the ability of monomers to nucleate or elongate. Cross-seeding or coaggregation may therefore represent an important contribution in the in vivo formation of assemblies believed to be important in disease.
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| 48. |
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| 49. |
- Säll, Olof, 1980-, et al.
(författare)
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Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students
- 2023
-
Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 151
-
Tidskriftsartikel (refereegranskat)abstract
- The bacterium Neisseria meningitidis causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine N. meningitidis carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period. Meningococcal isolates were characterised using whole-genome sequencing. The carriage rate among the students was 9.1% (319/3488; 95% CI 8.2-10.1). Factors associated with higher carriage rate were age ≤22 years, previous tonsillectomy, cigarette smoking, drinking alcohol and attending parties, pubs and clubs. Female gender and sharing a household with children aged 0-9 years were associated with lower carriage. The most frequent genogroups were capsule null locus (cnl), group B and group Y and the most commonly identified clonal complexes (cc) were cc198 and cc23. Persistent carriage with the same meningococcal strain for 12 months was observed in two students. Follow-up times exceeding 12 months are recommended for future studies investigating long-term carriage of N. meningitidis.
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| 50. |
- Taha, Muhamed-Kheir, et al.
(författare)
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Defining the breakpoint for resistance to rifampicin in Neisseria meningitidis by rpoB sequencing
- 2009
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Clinical isolates of Neisseria meningitidis resistant to rifampicin are important to identify asthey lead to failure of chemoprophylaxis of meningococcal disease. However, theidentification of these isolates is hindered by the absence of a harmonized breakpoint despiteefforts of standardization. In the present study, a large number (n=352) of clinical N.meningitidis isolates from 12 mainly European countries and spanning over 25 years (1984 to2009) were examined. The collection comprised all clinical isolates with MIC 0.25 mg/lreceived by the national reference laboratories for meningococci in the participating countries(n=161). In addition, representative isolates displaying MIC of rifampicin <0.25 mg/l wereexamined (n=191). Phenotyping and genotyping of isolates were performed and a 660 bpDNA fragment of the rpoB gene was sequenced in all the included isolates. Sequencesdiffering by at least one nucleotide were defined as a unique rpoB allele (n=55). Geometricmeans of MIC were calculated for isolates displaying the same allele. All the clinical isolatesdisplaying MIC >1 mg/l of rifampicin possessed rpoB alleles with critical mutations (in total21 alleles), resulting in substitutions at the codon H552 and less frequently at nearby codons(S548 and S557). These alterations were absent in the alleles (n=34) found in all isolates withMIC 1 mg/l. Based on these findings, rifampicin susceptible isolates could be defined asthose with MIC 1 mg/l. A new web site was created based on the data from this work (http://neisseria.org/nm/typing/rpoB). The rifampicin resistant isolates belonged to diversegenetic lineages and provoked lower bacteremia levels in mice. This biological cost mayexplain the non-expansion of the rifampicin resistant isolates.
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