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Austin G. Hester Robert C. Murphy Charis J. Uhlson Priscilla Ivester Tammy C. Lee Susan Sergeant Leslie R. Miller Timothy D. Howard Rasika A. Mathias Floyd H. Chilton 《The Journal of biological chemistry》2014,289(32):22482-22489
Dramatic shifts in the Western diet have led to a marked increase in the dietary intake of the n-6 polyunsaturated fatty acid (PUFA), linoleic acid (LA). Dietary LA can then be converted to arachidonic acid (ARA) utilizing three enzymatic steps. Two of these steps are encoded for by the fatty acid desaturase (FADS) cluster (chromosome 11, 11q12.2-q13) and certain genetic variants within the cluster are highly associated with ARA levels. However, no study to date has examined whether these variants further influence pro-inflammatory, cyclooxygenase and lipoxygenase eicosanoid products. This study examined the impact of a highly influential FADS SNP, rs174537 on leukotriene, HETE, prostaglandin, and thromboxane biosynthesis in stimulated whole blood. Thirty subjects were genotyped at rs174537 (GG, n = 11; GT, n = 13; TT, n = 6), a panel of fatty acids from whole serum was analyzed, and precursor-to-product PUFA ratios were calculated as a marker of the capacity of tissues (particularly the liver) to synthesize long chain PUFAs. Eicosanoids produced by stimulated human blood were measured by LC-MS/MS. We observed an association between rs174537 and the ratio of ARA/LA, leukotriene B4, and 5-HETE but no effect on levels of cyclooxygenase products. Our results suggest that variation at rs174537 not only impacts the synthesis of ARA but the overall capacity of whole blood to synthesize 5-lipoxygenase products; these genotype-related changes in eicosanoid levels could have important implications in a variety of inflammatory diseases. 相似文献
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Pascal Vallotton Antoine M. van Oijen Cynthia B. Whitchurch Vladimir Gelfand Leslie Yeo Georgios Tsiavaliaris Stephanie Heinrich Elisa Dultz Karsten Weis David Grünwald 《Traffic (Copenhagen, Denmark)》2017,18(12):840-852
Object tracking is an instrumental tool supporting studies of cellular trafficking. There are three challenges in object tracking: the identification of targets; the precise determination of their position and boundaries; and the assembly of correct trajectories. This last challenge is particularly relevant when dealing with densely populated images with low signal‐to‐noise ratios—conditions that are often encountered in applications such as organelle tracking, virus particle tracking or single‐molecule imaging. We have developed a set of methods that can handle a wide variety of signal complexities. They are compiled into a free software package called Diatrack. Here we review its main features and utility in a range of applications, providing a survey of the dynamic imaging field together with recommendations for effective use. The performance of our framework is shown to compare favorably to a wide selection of custom‐developed algorithms, whether in terms of localization precision, processing speed or correctness of tracks. 相似文献
69.
Leslie Redpath J Bengtsson U DeSimone J Lao X Wang X Stanbridge EJ 《Radiation research》2003,159(1):57-71
We have studied the impact of TP53 status on the extent and nature of chromosome damage seen in human skin fibroblasts after gamma irradiation beyond the G1-phase checkpoint but prior to the G2-phase checkpoint. Mitotic cells were examined in the absence and presence of treatment with nocodazole and the yield of aberrations was scored as a function of time postirradiation. The results revealed substantially greater damage in the absence of nocodazole, indicating that damage was being masked in its presence. While metaphase aberrations were seen exclusively in the presence of nocodazole, anaphase aberrations were seen principally in its absence. Furthermore, these were mostly of an unseparated, or "sticky", type that showed separation of the chromatids in the centromeric region, indicating normal degradation of cohesin, with retention of adhesion further out on the chromatid arms. Using postirradiation BrdU labeling and the absence of nocodazole, we were able to identify mitotic figures up to the third postirradiation mitosis. Analysis of the data revealed that in cells wild-type for TP53 the aberrant anaphases were lost after the first postirradiation mitosis, although they were still found in gradually decreasing amounts into the second and third postirradiation mitoses in E6-expressing cells. The data indicate that the formation of these sticky anaphases is independent of TP53 status, an observation that is consistent with the TP53 independence of transient G2-phase arrest. However, the consequences of the formation of these lesions appear to be very different. In the case of cells wild-type for TP53 this is chronic G1-phase arrest, while in E6 cells it is anaphase catastrophe. 相似文献
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R D Leslie H P Volkmann M Poncher I Hanning H Orskov K G Alberti 《BMJ (Clinical research ed.)》1986,293(6551):840-842
Non-insulin dependent diabetes appears to be an inherited condition. A study of young offspring of non-insulin dependent diabetics was conducted to determine whether metabolic abnormalities could be found at a young age before clinical diabetes developed. Thirteen patients with non-insulin dependent diabetes were selected who fulfilled the following criteria: they had a sibling who also had non-insulin dependent diabetes, their spouse was non-diabetic, and the offspring were aged between 12 and 45 years, not diabetic, and available for study. All 32 offspring had a 75 g oral glucose tolerance test, and results in 13 of them, one randomly selected from each family, were compared with 13 controls of similar age, sex, and weight. The offspring had significantly higher fasting concentrations of glucose, higher proportions of haemoglobin A1, and higher concentrations of insulin, C peptide, and glucagon. After glucose challenge the increases in both glucose and C peptide concentrations were significantly greater in the offspring. These differences were maintained in all 32 offspring when compared with 18 controls of similar age, sex, and weight; seven of the 32 offspring had impaired glucose tolerance. These results indicate that young offspring of selected non-insulin dependent diabetics can show extensive metabolic changes including impaired glucose tolerance. These changes are associated with hyperinsulinaemia and hyperglucagonaemia. 相似文献