| 51. |
- Fa, M, et al.
(författare)
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Conformational studies of plasminogen activator inhibitor type 1 by fluorescence spectroscopy. Analysis of the reactive centre of inhibitory and substrate forms, and of their respective reactive-centre cleaved forms.
- 2000
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 267:12, s. 3729-34
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitors that belong to the serpin family are suicide inhibitors that control the major proteolytic cascades in eucaryotes. Recent data suggest that serpin inhibition involves reactive centre cleavage followed by loop insertion, whereby the covalently linked protease is translocated away from the initial docking site. However under certain circumstances, serpins can also be cleaved like a substrate by target proteases. In this report we have studied the conformation of the reactive centre of plasminogen activator inhibitor type 1 (PAI-1) mutants with inhibitory and substrate properties. The polarized steady-state and time-resolved fluorescence anisotropies were determined for BODIPY(R) probes attached to the P1' and P3 positions of the substrate and active forms of PAI-1. The fluorescence data suggest an extended orientational freedom of the probe in the reactive centre of the substrate form as compared to the active form, revealing that the conformation of the reactive centres differ. The intramolecular distance between the P1' and P3 residues in reactive centre cleaved inhibitory and substrate mutants of PAI-1, were determined by using the donor-donor energy migration (DDEM) method. The distances found were 57+/-4 A and 63+/-3 A, respectively, which is comparable to the distance obtained between the same residues when PAI-1 is in complex with urokinase-type plasminogen activator (uPA). Following reactive centre cleavage, our data suggest that the core of the inhibitory and substrate forms possesses an inherited ability of fully inserting the reactive centre loop into beta-sheet A. In the inhibitory forms of PAI-1 forming serpin-protease complexes, this ability leads to a translocation of the cognate protease from one pole of the inhibitor to the opposite one.
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| 52. |
- Francis, Matthew, 1969-, et al.
(författare)
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A study of the YopD-LcrH interaction from Yersinia pseudotuberculosis reveals a role for hydrophobic residues within the amphipathic domain of YopD
- 2000
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Ingår i: Molecular Microbiology. - : Blackwell Publishing. - 0950-382X .- 1365-2958. ; 38:1, s. 85-102
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Tidskriftsartikel (refereegranskat)abstract
- The enteropathogen Yersinia pseudotuberculosis is a model system used to study the molecular mechanisms by which Gram-negative pathogens translocate effector proteins into target eukaryotic cells by a common type III secretion machine. Of the numerous proteins produced by Y. pseudotuberculosis that act in concert to establish an infection, YopD (Yersiniaouter protein D) is a crucial component essential for yop regulation and Yop effector translocation. In this study, we describe the mechanisms by which YopD functions to control these processes. With the aid of the yeast two-hybrid system, we investigated the interaction between YopD and the cognate chaperone LcrH. We confirmed that non-secreted LcrH is necessary for YopD stabilization before secretion, presumably by forming a complex with YopD in the bacterial cytoplasm. At least in yeast, this complex depends upon the N-terminal domain and a C-terminal amphipathic α-helical domain of YopD. Introduction of amino acid substitutions within the hydrophobic side of the amphipathic α-helix abolished the YopD–LcrH interaction, indicating that hydrophobic, as opposed to electrostatic, forces of attraction are important for this process. Suppressor mutations isolated within LcrH could compensate for defects in the amphipathic domain of YopD to restore binding. Isolation of LcrH mutants unable to interact with wild-type YopD revealed no single domain responsible for YopD binding. The YopD and LcrH mutants generated in this study will be relevant tools for understanding YopD function during a Yersinia infection.
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| 53. |
- Gulliksson, Mårten, et al.
(författare)
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Perturbation identities for regularized Tikhonov inverses and weighted pseudoinverses
- 2000
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Ingår i: Bit: numerical mathematics. - 0006-3835. ; 40:3, s. 513-523
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Tidskriftsartikel (refereegranskat)abstract
- e consider the perturbation analysis of two important problems for solving ill-conditioned or rank-deficient linear least squares problems. The Tikhonov regularized problem is a linear least squares problem with a regularization term balancing the size of the residual against the size of the weighted solution. The weight matrix can be a non-square matrix (usually with fewer rows than columns). The minimum-norm problem is the minimization of the size of the weighted solutions given by the set of solutions to the, possibly rank-deficient, linear least squares problem. It is well known that the solution of the Tikhonov problem tends to the minimum-norm solution as the regularization parameter of the Tikhonov problem tends to zero. Using this fact and the generalized singular value decomposition enable us to make a perturbation analysis of the minimum-norm problem with perturbation results for the Tikhonov problem. From the analysis we attain perturbation identities for Tikhonov inverses and weighted pseudoinverses.
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| 54. |
- Gulliksson, Mårten, et al.
(författare)
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Perturbation theory for generalized and constrained linear least squares
- 2000
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Ingår i: Numerical Linear Algebra with Applications. - 1070-5325. ; 7:4, s. 181-195
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Tidskriftsartikel (refereegranskat)abstract
- The perturbation analysis of weighted and constrained rank-deficient linear least squares is difficult without the use of the augmented system of equations. In this paper a general form of the augmented system is used to get simple perturbation identities and perturbation bounds for the general linear least squares problem both for the full-rank and rank-deficient problem. Perturbation identities for the rank-deficient weighted and constrained case are found as a special case. Interesting perturbation bounds and condition numbers are derived that may be useful when considering the stability of a solution of the rank-deficient general least squares problem. Copyright © 2000 John Wiley & Sons, Ltd.
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| 55. |
- Gulliksson, Mårten, et al.
(författare)
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The use and properties of Tikhonov filter matrices.
- 2000
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Ingår i: SIAM Journal on Matrix Analysis and Applications. - 0895-4798. ; 22:1, s. 276-281
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Tidskriftsartikel (refereegranskat)abstract
- We consider the concept of Tikhonov filter matrices in connection with discrete ill-posed and rank-deficient linear problems. Important properties of the Tikhonov filter matrices are given together with their filtering and regularization effects. We also present new perturbation identities for the Tikhonov regularized linear least squares problem using filter matrices generalizing well-known perturbation identities for the linear least squares problem and pseudoinverses.
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| 56. |
- Hedengren, Marika, et al.
(författare)
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Expression and evolution of the Drosophila attacin/diptericin gene family.
- 2000
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Ingår i: Biochem Biophys Res Commun. - : Elsevier BV. - 0006-291X. ; 279:2, s. 574-81
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Tidskriftsartikel (refereegranskat)abstract
- We describe the genes for three new glycine-rich antimicrobial peptides in Drosophila, two attacins (AttC and AttD) and one diptericin (DptB). Their structures support the proposal that these glycine-rich antimicrobial peptides evolved from a common ancestor and are probably also related to proline-rich peptides such as drosocin. AttC is similar to the nearby AttA and AttB genes. AttD is more divergent and located on a different chromosome. Intriguingly, AttD may encode an intracellular attacin. DptB is linked in tandem to the closely related Diptericin. However, the DptB gene product contains a furin-like cleavage site and may be processed in an attacin-like fashion. All attacin and diptericin genes are induced after bacterial challenge. This induction is reduced in imd mutants, and unexpectedly also in Tl(-) mutants. The 18w mutation particularly affects the induction of AttC, which may be a useful marker for 18w signaling.
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| 57. |
- Henfridsson, Ola, et al.
(författare)
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Barriers to learning: on organizational defenses and vicious circles in technological adaptation
- 2000
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Ingår i: Accounting, Management and Information Technologies. - 0959-8022. ; 10:1, s. 33-52
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Tidskriftsartikel (refereegranskat)abstract
- On the basis of an interpretive case study, the authors explore the learning implications of introducing First Class in a social services department. The investigated case illustrates how learning efforts easily result in ''vicious circles''; the more learning is sought after, the more solid are the barriers to learning. In this case, the existence of certain organizational virtues - the learning organization and the notion of the professional social worker - were observed to have negative learning implications. Paradoxically, at the espoused level, these two virtues can be understood as healthy signs, although their existence as only virtues makes them basically opposed to learning. The results of this study contribute to existing theory about discontinuity in technological adaptation.
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| 58. |
- Hollander, Anna, et al.
(författare)
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Röster i rätten
- 2000
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Ingår i: Kulturella perspektiv - Svensk etnologisk tidskrift. - Umeå : Föreningen Kulturella perspektiv. - 1102-7908. ; :2, s. 35-40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Voices in CourtIn the ongoing project: Therapist and adverse party- cour! hearings about coercive intervention, weanalyze the communication process in court hearingsconcerning cases where citizens are subjectedto coercive measures (compulsory care for psychiatricpatients and drug abusers, social authorities'interventions to separate children from theirparents). The primary purpose is to analyze thedilemma ofbalancing two seemingly incompatibleroles for chief psychiatrists and social workers: tobe "on the client's side" in clinical and social worksettings, while acting as a formal adverse party tothe client in the courtroom.
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| 59. |
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| 60. |
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