| 1. |
- Blokzijl, A, et al.
(författare)
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Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3
- 2003
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 163:4, s. 723-728
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Tidskriftsartikel (refereegranskat)abstract
- The Notch and transforming growth factor-β (TGF-β) signaling pathways play critical roles in the control of cell fate during metazoan development. However, mechanisms of cross-talk and signal integration between the two systems are unknown. Here, we demonstrate a functional synergism between Notch and TGF-β signaling in the regulation of Hes-1, a direct target of the Notch pathway. Activation of TGF-β signaling up-regulated Hes-1 expression in vitro and in vivo. This effect was abrogated in myogenic cells by a dominant-negative form of CSL, an essential DNA-binding component of the Notch pathway. TGF-β regulated transcription from the Hes-1 promoter in a Notch-dependent manner, and the intracellular domain of Notch1 (NICD) cooperated synergistically with Smad3, an intracellular transducer of TGF-β signals, to induce the activation of synthetic promoters containing multimerized CSL- or Smad3-binding sites. NICD and Smad3 were shown to interact directly, both in vitro and in cells, in a ligand-dependent manner, and Smad3 could be recruited to CSL-binding sites on DNA in the presence of CSL and NICD. These findings indicate that Notch and TGF-β signals are integrated by direct protein–protein interactions between the signal-transducing intracellular elements from both pathways.
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| 2. |
- Dahlqvist, C, et al.
(författare)
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Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation
- 2003
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 130:24, s. 6089-6099
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Tidskriftsartikel (refereegranskat)abstract
- The bone morphogenetic protein (BMP) and Notch signaling pathways are crucial for cellular differentiation. In many cases, the two pathways act similarly; for example, to inhibit myogenic differentiation. It is not known whether this inhibition is caused by distinct mechanisms or by an interplay between Notch and BMP signaling. Here we demonstrate that functional Notch signaling is required for BMP4-mediated block of differentiation of muscle stem cells, i.e. satellite cells and the myogenic cell line C2C12. Addition of BMP4 during induction of differentiation dramatically reduced the number of differentiated satellite and C2C12 cells. Differentiation was substantially restored in BMP4-treated cultures by blocking Notch signaling using either theγ-secretase inhibitor L-685,458 or by introduction of a dominant-negative version of the Notch signal mediator CSL. BMP4 addition to C2C12 cells increased transcription of two immediate Notch responsive genes, Hes1 and Hey1, an effect that was abrogated by L-685,458. A 3 kb Hey1-promoter reporter construct was synergistically activated by the Notch 1 intracellular domain (Notch 1 ICD) and BMP4. The BMP4 mediator SMAD1 mimicked BMP activation of the Hey1 promoter. A synthetic Notch-responsive promoter containing no SMAD1 binding sites responded to SMAD1, indicating that DNA-binding activity of SMAD1 is not required for activation. Accordingly, Notch 1 ICD and SMAD1 interacted in binding experiments in vitro. Thus, the data presented here provide evidence for a direct interaction between the Notch and BMP signaling pathways, and indicate that Notch has a crucial role in the execution of certain aspects of BMP-mediated differentiation control.
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| 3. |
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| 4. |
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| 5. |
- Sandager, L, et al.
(författare)
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Storage lipid synthesis is non-essential in yeast
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:8, s. 6478-6482
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Tidskriftsartikel (refereegranskat)abstract
- Steryl esters and triacylglycerol (TAG) are the main storage lipids in eukaryotic cells. In the yeast Saccharomyces cerevisiae, these storage lipids accumulate during stationary growth phase within organelles known as lipid bodies. We have used single and multiple gene disruptions to study storage lipid synthesis in yeast. Four genes, ARE1, ARE2, DGA1, and LRO1, were found to contribute to TAG synthesis. The most significant contribution is made by DGA1, which encodes a novel acyl-CoA;diacylglycerol acyltransferase. Two of the genes, ARE1 and ARE2, are also involved in steryl ester synthesis. A yeast strain that lacks all four genes is viable and has no apparent growth defects under standard conditions. The strain is devoid of both TAG and steryl esters, and fluorescence microscopy revealed that it also lacks lipid bodies. We conclude that neither storage lipids nor lipid bodies are essential for growth in yeast.
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| 6. |
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| 7. |
- Bodman-Smith, M.D., et al.
(författare)
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Antibody response to the human stress protein BiP in rheumatoid arthritis
- 2004
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332 .- 1460-2172. ; 43:10, s. 1283-1287
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The human stress protein BiP (immunoglobulin binding protein) has been implicated in the pathogenesis of rheumatoid arthritis (RA) since BiP was found to stimulate synovial T-cell proliferation and anti-BiP antibodies are present in the serum of RA patients. The aim of this study was the development of a rapid and reproducible enzyme-linked immunosorbent assay (ELISA) to determine the specificity and sensitivity of anti-BiP antibodies in RA.Methods. An ELISA was developed that detected antibodies to BiP. The prevalence of anti-BiP antibodies was determined in sera from patients with early and established RA, sera antedating the onset of RA and sera from patients with other inflammatory and autoimmune diseases and healthy controls.Results. We have confirmed the increased prevalence of antibodies to BiP in the sera of a large cohort of patients with established RA (specificity 71% and sensitivity 73%) and early RA (specificity 65% and sensitivity 66%). In pre-disease sera, median 2.5 yr (interquartile range 1.1–4.7) before symptoms of joint disease, the sensitivity for anti-BiP antibodies was 45% and the specificity was 65% for the development of RA.Conclusion. Antibodies to BiP are found in the sera of patients with RA and in sera antedating the onset of RA.
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| 8. |
- Borzacchiello, A, et al.
(författare)
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Rheological characterization of vocal folds after injection augmentation in a preliminary animal study
- 2004
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Ingår i: Journal of bioactive and compatible polymers (Print). - London : Sage Publications. - 0883-9115 .- 1530-8030. ; 19:4, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- The investigation of vocal folds viscoelastic properties in an animal model (rabbit) after injection of various augmentation substances, 6 months after injection, is reported. The injected materials were: hyaluronan-based materials (Hylan B gel and Deflux(R)), cross-linked collagen (Zyplast(R)) and polytetrafluoroethylene (Teflon(R)). Rheological properties of the augmentation substances were also evaluated. The results from these animal experiments indicate that the viscoelastic properties of the vocal folds injected with Deflux(R), Zyplast(R) and Hylan B gel are similar to the healthy vocal folds (non-injected samples) used as control, thus demonstrating that these materials are good candidates for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.
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| 9. |
- Cvetkovic, J T, et al.
(författare)
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Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis
- 2002
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Ingår i: Rheumatology. - 1462-0324 .- 1462-0332. ; 41, s. 988-995
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To analyse the association of autoantibodies against cardiolipin (CL) and oxidized low density lipoproteins [copper-oxidized low density lipoprotein (oxLDL), malondialdehyde-modified LDL (MDA-LDL)] with rheumatoid arthritis (RA) and cardiovascular complications. Methods. One hundred and twenty-one patients with RA were consecutively included. Autoantibodies were determined by ELISA. Healthy individuals from the same region were used as controls. Results. Levels of IgG, IgM and IgA antibodies against MDA-LDL and CL, as well as IgG and IgA antibodies against oxLDL were increased in the patients (P<0.01). The prevalence of IgG, IgM and IgA antibodies against CL was higher than in the normal population (74, 82 and 14%, respectively). The prevalence of IgG and IgA antibodies against oxLDL was also significantly increased (35 and 25%, respectively) and so was the prevalence of IgG and IgM antibodies against MDA-LDL (17 and 26%, respectively) compared with controls. The levels of IgM and IgA antibodies against aCL and IgM against MDA-LDL were increased in patients with extra-articular manifestations. Patients who developed myocardial infarction had a higher prevalence of IgG antibodies against MDA-LDL (P=0.04). There were substantial correlations between the levels of antibodies against oxLDL, MDA-LDL and CL. Conclusions. RA patients had increased levels and prevalence of autoantibodies against CL, oxLDL and MDA-LDL, with associations to severity of disease and cardiovascular complications.
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| 10. |
- Dahlqvist, Ake, et al.
(författare)
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Sleep apnea and Down's syndrome
- 2003
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 123:9, s. 1094-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Obstructive sleep apnea has been reported to occur in 20-50% of children with Down's syndrome in case series of patients referred for evaluation of suspected sleep apnea. In this population-based controlled study, we aimed to investigate whether sleep apnea is related to Down's syndrome.MATERIAL AND METHODS: Every child aged 2-10 years with Down's syndrome residing in the Umeå healthcare district (n = 28) was invited to participate in the study, with their siblings acting as controls. Successful overnight sleep apnea recordings and echocardiography were performed in 17/21 children with Down's syndrome and in 21 controls.RESULTS: Obstructive sleep apnea could not be diagnosed, either in children with Down's syndrome or in the control children. The apnea-hypopnea index in the children with Down's syndrome was 1.2 +/- 1.5 and did not differ from that in controls. Snoring and hypertrophy of the tonsils were more common in children with Down's syndrome than in controls. Children with Down's syndrome slept for a shorter time (p < 0.001) and changed body position more often (p < 0.05) than the control children.CONCLUSIONS: Snoring, restless sleep and hypertrophy of the tonsils were common among children with Down's syndrome. Obstructive sleep apnea was, however, not related to Down's syndrome in the present population-based controlled study.
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