| 1. |
- Bergquist, Helen, 1979-, et al.
(författare)
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Structure-Specific Recognition of Friedreich’s Ataxia (GAA)n Repeats by Benzoquinoquinoxaline Derivatives
- 2009
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 10:16, s. 2629-2637
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Tidskriftsartikel (refereegranskat)abstract
- Expansion of GAA triplet repeats in intron 1 of the FXN gene reduces frataxin expression and causes Friedreich's ataxia. (GAA)nrepeats form non-B-DNA structures, including triple helix H-DNA and higher-order structures (sticky DNA). In the proposed mechanisms of frataxin gene silencing, central unanswered questions involve the characterization of non-B-DNA structure(s) that are strongly suggested to play a role in frataxin expression. Here we examined (GAA)nbinding by triplex-stabilizing benzoquinoquinoxaline (BQQ) and the corresponding triplex-DNA-cleaving BQQ-1,10-phenanthroline (BQQ-OP) compounds. We also examined the ability of these compounds to act as structural probes for H-DNA formation within higher-order structures at pathological frataxin sequences in plasmids. DNA-complex-formation analyses with a gel-mobility-shift assay and sequence-specific probing of H-DNA-forming (GAA)nsequences by single-strand oligonucleotides and triplex-directed cleavage demonstrated that a parallel pyrimidine (rather than purine) triplex is the more stable motif formed at (GAA)nrepeats under physiologically relevant conditions.
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| 2. |
- Pinkner, Jerome S., et al.
(författare)
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Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washtington : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:47, s. 17897-17902
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Tidskriftsartikel (refereegranskat)abstract
- A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone–usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by 90% in laboratory and clinical E. coli strains. The structure of the pilicide bound to the P pilus chaperone PapD revealed that the pilicide bound to the surface of the chaperone known to interact with the usher, the outer-membrane assembly platform where pili are assembled. Point mutations in the pilicide-binding site dramatically reduced pilus formation but did not block the ability of PapD to bind subunits and mediate their folding. Surface plasmon resonance experiments confirmed that the pilicide interfered with the binding of chaperone–subunit complexes to the usher. These pilicides thus target key virulence factors in pathogenic bacteria and represent a promising proof of concept for developing drugs that function by targeting virulence factors.
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| 3. |
- Sabado, Rachel L., et al.
(författare)
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Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1
- 2007
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 37:7, s. 1752-1763
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Tidskriftsartikel (refereegranskat)abstract
- The outcome following HIV infection depends on the nature and durability of the HIV-specific T cell response induced initially. The activation of protective T cell responses depends upon dendritic cells (DC), antigen-presenting cells which have the capacity to process and present viral antigens. DC pulsed with aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune responses and promote virologic control in chronically HIV-1-infected subjects. To gain an understanding of this phenomenon, we characterized the steps involved in the presentation of antigens derived from aldrithiol-2-treated vs. infectious HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C-type lectins expressed by the DC. Inhibitor studies showed that presentation on MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner, both at the cell surface and within endosomes, and access to the classical endosomal processing pathway. MHC class II presentation of HIV-associated antigens was dependent on active endocytosis, probably receptor-mediated, and subsequent degradation of virions in acidified endosomes in the DC. Our study brings forth new facts regarding the binding, uptake, and processing of chemically inactivated virions leading to efficient antigen presentation and should aid in the design of more effective HIV vaccines. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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| 4. |
- Theander, Eva, et al.
(författare)
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Vad händer om man ser patienten som expert?
- 2008
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Ingår i: Incitament. - 1103-503X. ; 17:5, s. 301-302
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- I vårt arbete har vi tillsammans identifierat olika problem i njursviktmottagningens verksamhet. Vi har också påbörjat arbetet med att förändra verksamheten och utvärdera denna förändring.
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| 5. |
- Theander, Eva, et al.
(författare)
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Vad händer om man ser patienten som expert?
- 2008
-
Ingår i: Incitament. - 1103-503X. ; 17:5, s. 301-302
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- I vårt arbete har vi tillsammans identifierat olika problem i njursviktmottagningens verksamhet. Vi har också påbörjat arbetet med att förändra verksamheten och utvärdera denna förändring.
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