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- Hao, X. J., et al.
(författare)
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Dendrimers as scaffolds for multifunctional reversible addition-fragmentation chain transfer agents : Syntheses and polymerization
- 2004
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Ingår i: Journal of Polymer Science Part A. - : Wiley. - 0887-624X .- 1099-0518. ; 42:23, s. 5877-5890
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and characterization of novel first- and second-generation true dendritic reversible addition-fragmentation chain transfer (RAFT) agents carrying 6 or 12 pendant 3-benzylsulfanylthiocarbonylsulfanylpropionic acid RAFT end groups with Z-group architecture based on 1,1,1-hydroxyphenyl ethane and trimethylolpropane cores are described in detail. The multifunctional dendritic RAFT agents have been used to prepare star polymers of poly(butyl acrylate) (PBA) and polystyrene (PS) of narrow polydispersities (1.4 < polydispersity index < 1.1 for PBA and 1.5 < polydispersity index < 1.3 for PS) via bulk free-radical polymerization at 60 degreesC. The novel dendrimer-based multifunctional RAFT agents effect an efficient living polymerization process, as evidenced by the linear evolution of the number-average molecular weight (M.) with the monomer-polymer conversion, yielding star polymers with molecular weights of up to M-n = 160,000 g mol(-1) for PBA (based on a linear PBA calibration) and up to M. = 70,000 g mol(-1) for PS (based on a linear PS calibration). A structural change in the chemical nature of the dendritic core (i.e., 1,1,1-hydroxyphenyl ethane vs trimethylolpropane) has no influence on the observed molecular weight distributions. The star-shaped structure of the generated polymers has been confirmed through the cleavage of the pendant arms off the core of the star-shaped polymeric materials.
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| 2. |
- Huang, Xudong, et al.
(författare)
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Impaired cathepsin L gene expression in skeletal muscle is associated with type 2 diabetes.
- 2003
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 52:9, s. 2411-2418
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Tidskriftsartikel (refereegranskat)abstract
- To identify abnormally expressed genes associated with muscle insulin resistance or type 2 diabetes, we screened the mRNA populations using cDNA differential display combined with relative RT-PCR analysis from muscle biopsies of diabetes-prone C57BL/6J and diabetes-resistant NMRI mice fed with a high-fat or normal diet for 3 or 15 months. Six abnormally expressed genes were isolated from the mice after a 3-month fat feeding; one of them was cathepsin L. No significant difference in mRNA levels of these genes was observed between fat- and normal-diet conditions in either strains. However, cathepsin L mRNA levels in muscle were higher in normal diet–fed C57BL/6J mice compared with normal diet–fed NMRI mice at 3 months (0.72 ± 0.04 vs. 0.51 ± 0.04 relative units, P < 0.01, n = 8–10) and at 15 months (0.41 ± 0.05 vs. 0.27 ± 0.04 relative units, P = 0.01, n = 9–10). Further, cathepsin L mRNA levels in muscle correlated inversely with plasma glucose in both strains regardless of diets at 3 (r = −0.49, P < 0.01, n = 31) and 15 (r = −0.42, P = 0.007, n = 39) months. To study whether cathepsin L plays a role in human diabetes, we measured cathepsin L mRNA levels in muscle biopsies taken before and after an insulin clamp from 12 monozygotic twin pairs discordant for type 2 diabetes and from 12 control subjects. Basal cathepsin L mRNA levels were not significantly different between the study groups. Insulin infusion increased cathepsin L mRNA levels in control subjects from 1.03 ± 0.30 to 1.90 ± 0.32 relative units (P = 0.03). Postclamp cathepsin L mRNA levels were lower in diabetic twins but similar in nondiabetic twins compared with control subjects (0.66 ± 0.22, 1.16 ± 0.18 vs. 1.38 ± 0.21 relative units, P < 0.02, NS, respectively). Further, postclamp cathepsin L mRNA levels were correlated with insulin-mediated glucose uptake (r = 0.37, P = 0.03), particularly, with glucose oxidation (r = 0.37, P = 0.03), and fasting glucose concentrations (r = −0.45, P < 0.01) across all three study groups. In conclusion, muscle cathepsin L gene expression is increased in diabetes-prone mice and related to glucose tolerance. In humans, insulin-stimulated cathepsin L expression in skeletal muscle is impaired in diabetic but not in nondiabetic monozygotic twins, suggesting that the changes may be secondary to impaired glucose metabolism.
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| 7. |
- Ling, Charlotte, et al.
(författare)
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Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins.
- 2004
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 114:10, s. 1518-1526
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Tidskriftsartikel (refereegranskat)abstract
- Genetic and environmental factors contribute to age-dependent susceptibility to type 2 diabetes. Recent studies have reported reduced expression of PPAR{gamma} coactivator 1{alpha} (PGC-1{alpha}) and PGC-1ß genes in skeletal muscle from type 2 diabetic patients, but it is not known whether this is an inherited or acquired defect. To address this question we studied expression of these genes in muscle biopsies obtained from young and elderly dizygotic and monozygotic twins without known diabetes before and after insulin stimulation and related the expression to a Gly482Ser variant in the PGC-1{alpha} gene. Insulin increased and aging reduced skeletal muscle PGC-1{alpha} and PGC-1ß mRNA levels. This age-dependent decrease in muscle gene expression was partially heritable and influenced by the PGC-1{alpha} Gly482Ser polymorphism. In addition, sex, birth weight, and aerobic capacity influenced expression of PGC-1{alpha} in a complex fashion. Whereas expression of PGC-1{alpha} in muscle was positively related to insulin-stimulated glucose uptake and oxidation, PGC-1ß expression was positively related to fat oxidation and nonoxidative glucose metabolism. We conclude that skeletal muscle PGC-1{alpha} and PGC-1ß expression are stimulated by insulin and reduced by aging. The data also suggest different regulatory functions for PGC-1{alpha} and PGC-1ß on glucose and fat oxidation in muscle cells. The finding that the age-dependent decrease in the expression of these key genes regulating oxidative phosphorylation is under genetic control could provide an explanation by which an environmental trigger (age) modifies genetic susceptibility to type 2 diabetes.
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| 8. |
- Mootha, VK, et al.
(författare)
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PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
- 2003
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 34:3, s. 267-273
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Tidskriftsartikel (refereegranskat)abstract
- DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.
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