| 1. |
- Chilkova, Olga, et al.
(författare)
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The eukaryotic leading and lagging strand DNA polymerases are loaded onto primer-ends via separate mechanisms but have comparable processivity in the presence of PCNA.
- 2007
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 35:19, s. 6588-6597
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae DNA polymerase delta (Pol delta) and DNA polymerase epsilon (Pol epsilon) are replicative DNA polymerases at the replication fork. Both enzymes are stimulated by PCNA, although to different levels. To understand why and to explore the interaction with PCNA, we compared Pol delta and Pol epsilon in physical interactions with PCNA and nucleic acids (with or without RPA), and in functional assays measuring activity and processivity. Using surface plasmon resonance technique, we show that Pol epsilon has a high affinity for DNA, but a low affinity for PCNA. In contrast, Pol delta has a low affinity for DNA and a high affinity for PCNA. The true processivity of Pol delta and Pol epsilon was measured for the first time in the presence of RPA, PCNA and RFC on single-stranded DNA. Remarkably, in the presence of PCNA, the processivity of Pol delta and Pol epsilon on RPA-coated DNA is comparable. Finally, more PCNA molecules were found on the template after it was replicated by Pol epsilon when compared to Pol delta. We conclude that Pol epsilon and Pol delta exhibit comparable processivity, but are loaded on the primer-end via different mechanisms.
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| 2. |
- Strömberg, C. A. E., et al.
(författare)
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Palaeoecology of a Middle Miocene lake in China: preliminary interpretations based on phytoliths from the Shanwang Basin
- 2007
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Ingår i: Vertebrata PalAsiatica. ; 45, s. 145-160
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Tidskriftsartikel (refereegranskat)abstract
- The lacustrine Early to Middle Miocene Shanwang Formation contains an exceptionally well preserved biota including insects, plants, and vertebrates that has been subject to intense study. Palaeoecological work on plant macrofossils and palynofloras indicate that the locality represents a forest under a humid, warm-temperate to subtropical climate that remained rather stable during the deposition of the formation. This interpretation is supported by fossil vertebrates such as bats and tapirs discovered in the Shanwang section. However, to date no information has been available on the presence, abundance, and taxonomic composition of grasses at this locality. Here, we report on phytoliths extracted from six samples from the Shanwang Formation, providing new evidence of the vegetation that grew around the lake. The phytolith assemblages contain well-preserved and abundant grass phytoliths, forest indicator phytoliths from dicotyledonous plants, and infrequent palm phytoliths. The grass phytoliths consist of forms produced by C,IC4 PACCAD grasses and pooids, with a minor component of morphotypes thought to derive from closed-habitat grasses. Our preliminary interpretation of these phytolith assemblages is that they reflect a lake-side wooded habitat and abundant helophytic to mesophytic grasses, with drier areas supporting pooid (and PACCAD) grasses. The data support the reconstruction of the Miocene Shanwang region as more humid and equable than presently. The Shanwang phytolith assemblages contrast with Miocene lacustrine phytolith assemblages from Turkey and the Great Plains of North America, which indicate grass communities characterized by diverse C3 pooids and different types of PACCAD grasses. Future research will determine whether this variability reflects large-scale biogeographic differences in grass communities or local, microclimate-related variation.
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| 3. |
- Hellebö Johanson, Else, 1969, et al.
(författare)
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No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes
- 2005
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Ingår i: Diabetes Metab Res Rev. - : Wiley. - 1520-7552. ; 21:4, s. 376-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.
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| 4. |
- Sandqvist, Madelene, 1974, et al.
(författare)
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Postprandial interstitial insulin concentrations in type 2 diabetes relatives
- 2006
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Ingår i: Eur J Clin Invest. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:6, s. 383-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.
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