| 1. |
- Heinzel, T., et al.
(författare)
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A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression
- 1997
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 387:6628, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional repression by nuclear receptors has been correlated to binding of the putative co-repressor, N-CoR. A complex has been identified that contains N-CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3, and which is required for both nuclear receptor- and Mad-dependent repression, but not for repression by transcription factors of the ets-domain family. These data predict that the ligand-induced switch of heterodimeric nuclear receptors from repressor to activator functions involves the exchange of complexes containing histone deacetylases with those that have histone acetylase activity.
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| 2. |
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| 3. |
- Söderström, Mats, et al.
(författare)
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Differential effects of nuclear receptor corepressor (N-CoR) expression levels on retinoic acid receptor-mediated repression support the existence of dynamically regulated corepressor complexes
- 1997
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Ingår i: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 11:6, s. 682-692
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormone and retinoic acid receptors are members of the nuclear receptor superfamily of ligand-dependent transcription factors that stimulate the transcription of target genes in the presence of activating ligands and repress transcription in their absence. Transcriptional repression by the thyroid hormone and retinoic acid receptors has been proposed to be mediated by the nuclear receptor corepressor, N-CoR, or the related factor, SMRT (silencing mediator of retinoic acid and thyroid hormone receptors). Recent studies have suggested that transcriptional repression by N-CoR involves a corepressor complex that also contains mSin3A/B and the histone deacetylase, RPD3. In this manuscript, we demonstrate that transcriptional repression by the retinoic acid receptor can be either positively or negatively regulated by changes in the levels of N-CoR expression, suggesting a relatively strict stoichiometric relationship between N-CoR and other components of the corepressor complex. Consistent with this interpretation, overexpression of several functionally defined domains of N-CoR also relieve repression by nuclear receptors. N-CoR is distributed throughout the nucleus in a nonuniform pattern, and a subpopulation becomes concentrated into several discrete dot structures when highly expressed. RPD3 is also widely distributed throughout the nucleus in a nonuniform pattern. Simultaneous imaging of RPD3 and N-CoR suggest that a subset of each of these proteins colocalize, consistent with the existence of coactivator complexes containing both proteins. In addition, a substantial fraction of both N-CoR and mSin3 A/B appear to be independently distributed. These observations suggest that interactions between RPD3 and Sin3/N-CoR complexes may be dynamically regulated.
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| 4. |
- Zabel, B A, et al.
(författare)
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Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis
- 1999
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Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 190:9, s. 1241-1256
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Tidskriftsartikel (refereegranskat)abstract
- TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen-positive (CLA(+)) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic alpha4beta7(-)CLA(-) memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti-GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.
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| 5. |
- Abdel-Halim, SM, et al.
(författare)
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Mutations in the promoter of adenylyl cyclase (AC)-III gene, overexpression of AC-III mRNA, and enhanced cAMP generation in islets from the spontaneously diabetic GK rat model of type 2 diabetes
- 1998
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 47:3, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- Glucose-induced insulin release is decreased in the spontaneously diabetic GK rat, a nonobese rodent model of type 2 diabetes. Forskolin restores the impaired insulin release in both the isolated perfused pancreas and isolated islets from these rats (Abdel-Halim et al., Diabetes 45:934-940, 1996). We demonstrate here that the insulinotropic effect of forskolin in the GK rat is due to increased generation of cAMP and that it is associated with overexpression of adenylyl cyclase (AC)-III mRNA and gene mutations. The AC-III mRNA overexpression was demonstrated by in situ hybridization using oligonucleotide probes binding to different regions of the rat AC-III mRNA. It was associated with the presence of two point mutations identified at positions -28 bp (A --> G) and -358 bp (A --> C) of the promoter region of the AC-III gene and was demonstrable in both GK rat islets and peripheral blood cells. Transfection of COS cells with a luciferase reporter gene system revealed up to 25-fold increased promoter activity of GK AC-III promoter when compared with normal rat promoter (P < 0.0001). In conclusion, forskolin restores the impaired insulin release in islets of the GK rat through enhanced cAMP generation. This is linked to overexpression of AC-III mRNA in GK islets due to two functional point mutations in the promoter region of the AC-III gene.
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| 6. |
- Kristiansson, P., et al.
(författare)
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Optical dot gain on newsprint determined with the Lund nuclear microprobe
- 1997
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - Amsterdam : Elsevier. - 0168-583X .- 1872-9584. ; 130:1-4, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- A technique for measuring optical dot gain, i.e. the relative difference between the actual screen dot and the optically perceived one, is presented. By combining measurements from the non-optical nuclear microprobe with data from image analyzing technique the optical dot gain can be determined. The procedure to reach pixel by pixel correlation on a micrometer scale is discussed. In the newsprint sample studied in this investigation a typical optical dot gain between 15 and 20% was deduced. The variation in the optical dot gain was correlated with other characteristic parameters of the print and newsprint and especially a positive correlation to the mass density of the newsprint was observed. (C) 1997 Elsevier Science Ltd.
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| 7. |
- Liedberg, Bo, et al.
(författare)
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Self-assembly of alpha-functionalized terthiophenes on gold
- 1997
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Ingår i: JOURNAL OF PHYSICAL CHEMISTRY B. - : AMER CHEMICAL SOC. - 1089-5647 .- 1520-6106 .- 1520-5207. ; 101:31, s. 5951-5962
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Tidskriftsartikel (refereegranskat)abstract
- alpha-Functionalized terthiophenes containing disulfide (-S-T-3-H)(2) and alkanethiol (HS-(CH2)(11)-T-3-H) anchoring groups have been synthesized for direct immobilization onto gold. Monolayer structures of these compounds are prepared by spontaneous assembly from ethanol solutions on evaporated gold substrates and thoroughly characterized by ellipsometry, contact angle goniometry, infrared and X-ray photoelectron spectroscopy, and cyclic voltammetry. The two molecules coordinate to the gold substrate exclusively via the anchoring groups upon formation of gold-thiolate bonds. The kinetics of monolayer formation vary dramatically for the two compounds. The alkanethiol analogue assembles rapidly, within a few minutes, and forms a densely packed and highly organized monolayer, with the alkyl chains in an almost perfect all-trans conformation and the C-alpha-C-alpha axis of the alpha-T-3 units tilted about 14 degrees away from the surface normal. The assembly process is much slower for the disulfide, but an organized monolayer with an average alpha-T-3 chain tilt of about 33 degrees will eventually form when the assembly is allowed to equilibrate with a solution containing the disulfide for at least 1 day. Moreover, the two monolayer assemblies also display a remarkably different electrochemical, behavior. The heterogeneous electron-transfer rate at the disulfide-covered gold substrate is almost indistinguishable from that at bare gold, suggesting that the assembly contains a large number of easily accessible defects. An alternative mechanism for explaining the large electron-transfer rate involving electronic coupling via the conjugated pi-system of the alpha-T-3 units is also proposed. The electrochemical response is significantly reduced for the HS-(CH2)(11)-T-3-H assembly, but another type of defects, the so-called shallow defects originating from sparsely populated areas on the electrode surface, can be identified.
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| 8. |
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| 9. |
- Yang, Zhongping, et al.
(författare)
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Preparation and characterization of mixed monolayer assemblies composed of thiol analogues of cholesterol and fatty acid
- 1997
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Ingår i: Langmuir. - : American Chemical Society. - 0743-7463 .- 1520-5827. ; 13:12, s. 3210-3218
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Tidskriftsartikel (refereegranskat)abstract
- Mixed self-assembled monolayers provide an attractive model system for investigating the role of different molecules in biological membranes. This paper describes the preparation and characterization of a novel type of mixed monolayer assemblies composed of thiol analogues of cholesterol and fatty acid. The mixed: monolayers are prepared by coadsorbing 11-mercaptoundecanoic acid (MUA) and thiocholesterol(cholest-5-ene-3 beta-thiol, TC) from solution directly onto evaporated gold surfaces. The influence of TC on the molecular composition and conformation in the mixed monolayer is analyzed by using a combination of infrared reflection-absorption spectroscopy (IRAS), X-ray photoelectron spectroscopy (XPS), ellipsometry, contact angle measurement, and cyclic voltammetry. The results indicate that the TC molecules maintain their conformation in the mixed monolayers, whereas the MUA molecules display a significantly more disordered conformation as compared to the MUA molecules in the pure monolayer. Cyclic voltammetry shows that the mixed monolayers are more densely packed and less permeable than the pure TC and MUA monolayers. The kinetics of the coadsorption of TC and MUA from ethanol indicates that adsorption of TC initially is strongly preferred over MUA but that MUA dominates over TC at long coadsorption times. This is because there is a larger energy gain per unit area in forming monolayers with MUA, Further, it is also seen that the number of molecules per unit area changes with the molecular composition, as a consequence of the different sizes of TC and MUA. We present herein a method for calculating the mole fraction of TC on the gold surface, (chi TC), which accounts for this variation. As a consequence of the dissimilar size and shape of the two molecules, the wetting properties of the mixed monolayer are found to be mainly governed by the fractional area of TC, rather than by the molecular composition of TC, (chi TC).
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| 10. |
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